JUNE 27 , 2016 VOLUME 27, NO. 123BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS
BIOWORLD TODAYTM
THE DAILY BIOPHARMACEUTICAL NEWS SOURCE
See Diagnostics, page 3 See Infection, page 4
See NDFC, page 8
See Jardiance, page 6 See United, page 7See Brexit, page 5
S E A R C H I N G F O R S U P E R B U G ’ S K R Y P T O N I T E
EUROPE
CHINA
REGULATORY
IN THE CLINIC
ANALYSIS
See Frontier, page 9
BENCH PRESS
BioWorld Senior Science Editor Anette Breindl takes a closer look at translational medicine
Read this week’s edition
Resistant superbug’s arrival highlights the need for more effective diagnosticsBy Liz Hollis, Staff Writer
Politicians and medical experts worldwide alike have decried the lack of innovation in antibiotics – an area that has been neglected for three decades – but another area is turning out to be just as important: diagnostics.“Without rapid, precision Dx to target therapy, physicians generally treat empirically, prescribing widely available and inexpensive broad-spectrum antibiotics,” according to an executive briefing paper authored by Jonathan Kfoury and Alex Vadas, managing directors, and T.J. Bilodeau, U.S. practice manager, all of L.E.K.
Cut the blame game: Infection control is a shared problemBy Amanda Pedersen, Senior Staff Writer
Superbugs tend to evoke a lot of finger-pointing and the blame often spreads as
wide and fast as the outbreaks themselves. But if the industry
See I.V. catheter, p. 4, and AMR supple-
ment, attached
Frontier’s pain patch hits phase II endpoints By Shannon Ellis, Staff Writer
SHANGHAI – A transdermal pain patch being studied by Frontier Biotechnologies Inc., of Nanjing, China, has met its primary endpoints in a U.S. phase II trial of 146 patients with chronic lower back pain. The super-thin patch – only 200
Newly formed NDFC: Where China’s life sciences elite meet By Shannon Ellis, Staff Writer
SHANGHAI – Discovering and developing new drugs is hard anywhere in the world but perhaps especially so in China where it is a relatively new pursuit. For those who take on the challenge of
CAN REATA LASSO THE MARKET?
PAH, humbug: Confident United sees friendly skies despite skeptic headwindBy Randy Osborne, Staff Writer
Pointing to a “brand-new ball game” with vasodilator Orenitram (treprostinil extended-release tablets) in pulmonary arterial hypertension (PAH) and “tough
Jardiance CV death risk vote nears for FDA advisorsBy Michael Fitzhugh, Staff Writer
FDA reviewers told agency advisors in briefing docs released Friday that Jardiance (empagliflozin) postmarket data show “substantial evidence” that, for certain adults with type 2 diabetes,
‘DARK DAY FOR U.K. SCIENCE’
Industry reacts as Britain stuns with vote to leave EUBy Nuala Moran, Staff Writer
LONDON – There is alarm, concern and even heartbreak across the biotech and pharma industry and among leading scientists at the vote to leave the EU.
MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 2 OF 14
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FINANCINGS
Crispr Therapeutics AG, of Basel, Switzerland, closed an additional $38 million of its series B financing, which brings the total to almost $140 million. The previous series B investment was led by Vertex Pharmaceuticals Inc., of Boston, and Bayer Global Investments, an affiliate of Bayer AG, of Leverkusen, Germany, as part of the company’s strategic investment in Crispr Therapeutics. This second, oversubscribed closing includes several new institutional investors and specialized health care funds. Participating investors include Franklin Templeton Investments, New Leaf Venture Partners, funds advised by Clough Capital Partners LP and Wellington Capital Management LLP, and other undisclosed funds specializing in life sciences. (See BioWorld Today, Oct. 27, 2015, and Dec. 22, 2105.)
OTHER NEWS TO NOTE
Janssen Inc., of Toronto, a unit of Johnson & Johnson, said Health Canada approved Simponi (golimumab) for the treatment of adults with severe active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein and/or magnetic resonance imaging evidence, who have had an inadequate response to or are intolerant to nonsteroidal anti-inflammatory drugs. It is the fifth indication for Simponi in Canada, which was approved originally in 2009 for adults with moderately to severely active rheumatoid arthritis.Medivation Inc., of South San Francisco, said its ongoing battle to fend off a takeover by Paris-based Sanofi SA continued on June 23 with a letter to stockholders countering Sanofi’s claims about Medivation’s value. The letter urges Medivation’s shareholders to either throw away materials seeking their consent to replace Medivation’s board with a slate of Sanofi’s choosing or revoke consent if they already provided it. The two companies have been locked in a stalemate since March, when Sanofi lobbed an unsolicited $9.3 billion cash bid for
Medivation, which values it at $52.50 per share. (See BioWorld Today, May 26, 2016.)Paion AG, of Aachen, Germany, and Cosmo Technologies Ltd., a subsidiary of Dublin-based Cosmo Pharmaceuticals NV, entered a license agreement granting Cosmo exclusive rights to develop and commercialize remimazolam, an ultra-short-acting intravenous benzodiazepine sedative/anesthetic, in the U.S. Under the terms, Paion will receive a €10 million (US$11.1 million) up-front license fee and will be entitled to receive additional payments of up to €42.5 million contingent upon certain milestones related to the regulatory approval process and, upon commercialization in the U.S., tiered royalties ranging from 20 percent to 25 percent. At the same time, Granell Strategic Investment Fund Ltd., another subsidiary of Cosmo, entered an investment agreement with Paion, pursuant to which it has committed to invest €10 million in shares of Paion, which resolved to issue about 5.1 million shares priced at €1.90 apiece for a total of €9.6 million. The remaining €400,000 will be invested at a later date. Upon completion of the private placement, Granell will hold about 9 percent of Paion’s issued share capital.Pfizer Inc., of New York, said its $5.2 billion takeover of Anacor Pharmaceuticals Inc., of Palo Alto, Calif., is complete. Under the terms of the transaction, each outstanding share of Anacor common stock has been converted into the right to receive $99.25 net in cash. The rationale for the merger primarily focused on the potential for a near-term U.S. product launch of crisaborole for atopic dermatitis. (See BioWorld Today, June 2, 2016.)
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ADVANTAGES/DISADVANTAGES OF ESTABLISHED TECHNOLOGIES TO DETERMINE ANTIMICROBIAL RESISTANCE
Culture:Advantages:• Works well in determining phenotypic resistance (culture the organism with antimicrobials)• Is inexpensive• Is broadly available (legacy technology, most hospitals offer it)
Disadvantages:• Slow (serious infections may often require empiric treatment before they have resistance data)• Not amenable to point of care (slow, cumbersome)
PCR:Advantages:• Can be a lot faster (emerging point of care can get below 60 minutes)• Is sensitive• Can be amenable to point of care, in some instances (not blood stream infections)
Disadvantages:• Is expensive relative to culture • Presents reimbursement challenges• Not broadly available, but that is improving with lower cost, point of care solutions
Source: Alex Vadas, managing director within L.E.K.’s BioPharma and Life Sciences Group in Los Angeles
See Diagnostics, page 10
Consulting’s Biopharma and Life Sciences practice. That situation, however, is leading to poor patient outcomes and growing antibiotic resistance. Once those broad-spectrum antibiotics fail to help a patient or susceptibility data return from the lab – a process that can take two to four days – the doctor then considers a novel or more targeted antibiotic.With the decline in antibiotic development since the 1980s, there are grave concerns that the number of deaths related to infections could rise sharply. According to the May report released by the U.K.’s Lord Jim O’Neill, who formerly served as chief economist at Goldman Sachs and now is commercial secretary to the Treasury, without some sort of policy intervention, deaths related to antimicrobial agents could climb from the current 700,000 a year to 10 million a year by 2050.The report encourages the development of new, rapid diagnostics to reduce the unnecessary use of antimicrobials, as there is currently mostly guesswork involved. “The process has remained basically unchanged in decades; most of these tests are lab-based and would look familiar to a doctor trained in the 1950s, using processes that originated in the 1860s.” The problem: the lack of a market for new tests, the report asserts.
CHALLENGES TO EARLY DIAGNOSTIC TESTINGIn their executive insights paper, the L.E.K. team identified
challenges that constrain the use of diagnostic testing in early treatment decisions for serious bacterial infections, most notably slow turnaround time, the lack of capacity to identify the causal pathogen and its susceptibility profile, laboratory workflow challenges, and cost and reimbursement issues.“While culture-based methods are the gold standard in effectively identifying the causal pathogen and testing its susceptibility to antimicrobial agents, these methods take two to four days, forcing physicians to treat patients empirically until definitive test results arrive,” the team wrote.Why does the process take so long? After obtaining a positive blood culture, resistance testing may be done either by using antibiotic sensitivity testing or a molecular approach using polymerase chain reaction (PCR) and a test for a set of known mutations, Vadas told BioWorld Today. “Regardless of the approach, you still need to culture the blood up front, which adds 24-plus hours to the testing timeline,” he added. “In terms of solutions, low-cost, broadly available PCR solutions are in development and may have applicability for certain types of infections,” he added. He touched on the promise of direct detection, which allows for the discovery of a pathogen from the blood without culture. An example of a company studying that method is Geneweave, which was acquired by Basel, Switzerland-based Roche Holding AG last year. (See BioWorld Today, Aug. 14, 2015.)
MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 4 OF 14
What’s inside your I.V. catheter?By Amanda Pedersen, Staff Writer
Having spent the bulk of his medical career researching infections in cancer patients undergoing chemotherapy, Stephen Schimpff, a retired CEO from the Baltimore-based University of Maryland Medical Center, knows a lot about how hospitals can make patients sick.“We know, in many cases, how to reduce and how to prevent infections, but in many cases we just don’t do it,” Schimpff told BioWorld Today. “An I.V. catheter should be put in sterilely but it’s often not, or it’s left in too long.”I.V. catheters are a lot like the stones found in little streams that run through the woods. The slimy covering on one of those stones in the stream is a biofilm that has formed over a layer of bacteria that has formed on the surface of the rock, Schimpff said.“It’s not just a layer of bacteria. It’s a layer of bacteria laid down in a matrix of protein and other chemicals and that biofilm protects them,” he said. “The bacteria are quite alive and quite
protected, so you can pour chlorine on them and it won’t kill them because they’re inside this protective coating.”The same thing happens inside the tiny plastic tubes used to deliver drugs and fluids directly into patients’ bloodstreams.Cancer patients undergoing chemotherapy often receive a central venous catheter, which is threaded through a needle to end in a large vein in their chest, near the heart, where there is a lot of blood flow and the drug is diluted quickly. Early in Schimpff’s career he occasionally had cancer patients get sick after having one of those catheters. That’s because the catheters furnish bacteria with a superhighway that leads straight into the bloodstream. And biofilms – just like the ones that protect bacteria on rocks in a stream – will eventually form both on the inside and the outside of the catheters.“I met a guy from Canada who said, ‘Take one of those catheters out sometime and send it to me ... I’m going to send you the picture back.’” Schimpff said. “So he did. Inside of these little thin catheters that had been inside veins was this film the entire length of the catheter, and we never knew it. It’s actually amazing that patients didn’t get sick more often.” //
learned anything from last year’s high-profile duodenoscope debacle it’s that infection control is a shared responsibility. Manufacturers, third-party reprocessing firms, hospitals, regulatory bodies and lawmakers all have a role to play in protecting patients from those deadly diseases.For one of the largest endoscopic device makers, owning up to its share of that responsibility has proved to be a remarkably lengthy and costly lesson. Olympus Corp. of the Americas is in the middle of a major recall of its TJF-Q180V duodenoscopes because the scopes have been linked to widespread carbapenem-resistant Enterobacteriaceae (CRE) infections. Some CRE bacteria have become resistant to most available antibiotics, and are able to kill up to half the patients they infect, according to the U.S. CDC. The Center Valley, Pa.-based company allegedly warned European regulators in 2013 and 2014 about the device’s potential to spread infection, but did not alert U.S. hospitals until a U.S. Senate investigation brought the issue to light earlier this year. The report, which came from the office of Sen. Patty Murray (D-Wash.), cited 25 outbreaks of infections across the country and in Europe involving nearly 200 U.S. patients. The Senate report came out soon after the FDA cleared a new, easier-to-clean version of Olympus’ duodenoscope that features a redesigned component intended to provide a tighter seal in an effort to reduce the risk of infection. Olympus said it will replace the sealing mechanism on about 4,400 devices currently in use by August.While Olympus has taken the most heat for the problem, all duodenoscopes – including those sold by Fujifilm and Pentax – are inherently difficult to clean because of the See Infection, page 13
moving elevator mechanism at the tip where patient fluids and tissue can potentially get inside the device. Duodenoscopes provide a minimally invasive way of draining fluids from pancreatic and biliary ducts that are blocked by problems like tumors or gallstones. Similar reusable endoscopes such as bronchoscopes and colonoscopes also carry a risk of transferring pathogens.Hospitals like the University of California Los Angeles’ Ronald Reagan Medical Center have started to sterilize duodenoscopes with ethylene oxide, but that method requires more wait time between use because the gas is so toxic. The longer sterilization process has driven up the demand for the devices, which are used in up to 600,000 U.S. procedures every year.
MAKING LEMONADE FROM DEADLY LEMONSJust as combat needs often drive medical innovation, disease outbreaks have opened up a big market opportunity for new infection control products. From tiny cameras that can see inside endoscopes to mobile apps and analytics software that tracks infectious patients during their hospital stay, medtech companies can’t be accused of sitting out of the superbug fight.Patient Safe Inc. has developed a new class of small diameter, near field inspection scopes designed to provide access to and imaging of the interior chambers, lumens and working channels of surgical devices, including endoscopes.The Sausalito, Calif.-based company was already in the process of bringing its Steriview infection control system to the U.S. market even before Olympus’ duodenoscope CRE problem surfaced, CEO Larry Gerrans told BioWorld Today. The system includes the company’s Stericam line of software-powered cameras for visual confirmation that endoscopes and other surgical tools are free of bacteria and fluid.
MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 5 OF 14
Brexit Continued from page 1“This is not the outcome the Bioindustry Association wanted,” Steve Bates, CEO told BioWorld Today.“Key questions about the regulation of medicine, access to the single market and talent, intellectual property and the precise nature of the future relationship of the U.K. with Europe, are now upon us,” Bates said.He was echoed by Mike Thompson, CEO of the Association of the British Pharmaceutical Industry, who said, “This creates immediate challenges for future investment, research and jobs in our industry in the U.K.”Similarly, member of parliament Nicola Blackwood, chair of the house of commons science and technology committee, said, “It is vital that the government moves quickly to reassure our scientists and their collaborators in Europe that the U.K. remains firmly open for business as a willing and reliable partner.”The committee will now be looking into the consequences of the vote for British science and the impact of the loss of EU R&D funding, Blackwood said. Earlier this month, the science and technology committee published an investigation into the effect of EU regulation on life sciences, which concluded the government needed to put in place a contingency plan to protect the sector in the event of a vote to leave. (See BioWorld Today, June 13, 2016.)U.K. scientists of international stature gave some very personal reactions to the referendum result, in which 17.4 million voted to leave the EU vs. 16.3 million in favor of remaining, on a turnout of 72 percent.“I am heartbroken and I have great concern for the future of British science,” said Anne Glover, former EU chief science adviser and now vice principal of Aberdeen University. “Our success in research and resulting impact relies heavily on our ability to be a full part of the EU science arrangements, and it is hard to see how they can be maintained upon a British exit,” she said.For Paul Nurse, Nobel laureate and director of the U.K.’s new translational science institute, The Francis Crick, the vote to leave is “a poor outcome and so bad for Britain. British scientists will have to work hard in the future to counter the isolationism of a British exit if our science is to continue to thrive,” he said.Venki Ramakrishnan, president of the U.K.’s most prestigious science body, the Royal Society, said EU R&D money is an essential supplement to national funding of science. “We must make sure that research …. is not short-changed and the government ensures that the overall level of science is maintained,” he said. Ramakrishnan added, “Any failure to maintain the free exchange of people and ideas between the U.K. and the international community, including the EU, could seriously
harm U.K. science.”Paul Boyle, vice chancellor of Leicester University, said, “This is a shocking result for the nation and its universities and a dark day for U.K. science. We need to offer support to our European colleagues and students who are working and studying in the U.K., and we need to begin campaigning immediately to protect the science budget.”
NEGOTIATING THE EXITWith no country having left the EU before, there is some uncharted territory to cross in negotiating withdrawal under article 50 of the EU’s Lisbon Treaty. The next step will be for the U.K. government to notify the European Commission of its intention to leave, which will start the gun on a two-year countdown to negotiate the terms.It is not clear as yet if the U.K. will cut itself off completely, or will have some form of associated membership like that held by Norway and Switzerland. However, that would involve adhering to the EU principle of free movement of labor, and with migration being one of the main issues in the referendum, it seems unlikely such a condition would be acceptable.The prime minister, David Cameron, who called the referendum and led the remain campaign announced he will stand down within the next three months, as soon as a successor is chosen by the Conservative Party. It will be up to the new prime minister to trigger article 50. Until the withdrawal negotiations are complete, the U.K. remains as a full member of the EU on exactly the same terms as today.Both Bates and Thompson want to see a taskforce set up with industry representation to work with government on setting out terms for negotiating the U.K.’s exit. As an EU agency, the EMA will have to be relocated from London, but Thompson hopes it will be possible for the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to maintain its status vis a vis its European counterparts and that medicines in the U.K. will continue to be regulated within the EMA framework.“I know from talking to colleagues in Europe how highly they regard the MHRA; that’s why it gets more files to review than any other agency, and they do want MHRA still on side,” Thompson told BioWorld Today.Bates agreed, saying, “The MHRA plays a crucial role in EU medicines regulation. It has got expertise and capabilities of global renown and has provided key thinking and leadership and engaged in the development of new ideas. It is important that this goes on, and that is recognized by others.” //
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Jardiance Continued from page 1the drug reduces the risk of cardiovascular death. They did not recommend that the advisors support label claims that the drug could reduce the risk of either hospitalization for heart failure (HF) or a composite of CV death (excluding fatal stroke) or hospitalization for HF.A vote by the advisory committee Tuesday supporting the addition of the CV risk benefit alone could help position Jardiance co-developers Boehringer Ingelheim Pharmaceuticals GmbH and Eli Lilly and Co. better against competitors, including Johnson & Johnson’s Invokana (canagliflozin) and Astrazeneca plc’s Farxiga (dapagliflozin). Furthermore, FDA approval of new language for the label could help the companies negotiate with payers for better formulary positioning, Credit Suisse analyst Vamil Divan told clients on Friday.“While it appears the FDA is only favorable towards including the reduction of CV death, we believe this is the most important one that the companies needed to find support for,” he said. “Given that the stock has been weak heading into this panel, we believe these documents should be a relief and, assuming the panel supports this view on Tuesday, should allow for further upside for LLY going forward.”The vote will inform FDA decisions this fall on two supplemental new drug applications seeking changes to the labels for both Jardiance and Synjardy, which combines empagliflozin and metformin.Discussions at the Endocrinologic and Metabolic Drugs Advisory Committee will delve into the results of the EMPA-REG Outcome trial. The postmarketing trial was required when Jardiance, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, was first approved in August 2014. Randomized, double-blind and event-driven, the trial compared two doses of empagliflozin to placebo across more than 7,000 patients with type 2 diabetes and established CV disease. Both doses and the placebo were added to standard-of-care diabetic treatments. The primary objective was to exclude the possibility that use of empagliflozin to control glycemia increased cardiovascular risk by 30 percent or more compared to use of alternate, standard-of-care, glycemic-lowering therapies.The trial’s pre-specified primary endpoint was the time to first occurrence of an adjudicated major adverse cardiovascular event (MACE), defined as an incident event of either CV death, nonfatal myocardial infarction (MI) or nonfatal stroke. It was to stop after 691 participants had experienced an adjudicated MACE event.The pre-specified secondary endpoint was the time to first occurrence of adjudicated CV death, nonfatal MI, nonfatal stroke and hospitalization for unstable angina (i.e., MACE+ or 4-point MACE).Jardiance was found to be both noninferior and superior to
placebo on the primary MACE endpoint (HR 0.86; 95 percent CI 0.74, 0.99; p = 0.04 for superiority) and noninferior but not superior to placebo on MACE+ (HR 0.89; 95 percent CI 0.78, 1.01; p = 0.08 for superiority).Now FDA advisors, including cardiologists, endocrinologists and statisticians, are slated to contemplate five questions around how to interpret the study’s results and two voting questions advising the FDA on the best way forward.First, advisors will be asked whether an interim unblinding or changes made to the trial protocol, endpoint definitions and analyses plan during the course of the study impact their confidence in concluding that excess CV risk was excluded and CV benefit was established. Some unblinding occurred as the trial was ongoing to support preapproval analyses and worldwide regulatory submissions.Interpretations of the nonfatal components in the composite endpoint (i.e., nonfatal myocardial infarction and nonfatal stroke), mortality, HF and renal findings in relation to the overall results will also be discussed.Finally, after voting on whether or not the EMPA-REG Outcome results line up with agency guidance requiring that it improve glycemic control while not resulting in an unacceptable rise in cardiovascular risk — a likely “yes” — the group will vote on whether there’s sufficient evidence to support a claim that it reduces CV mortality.New analyses from the trial announced during the recent American Diabetes Association Scientific Sessions in New Orleans showed risk reductions were consistent across age groups for cardiovascular outcomes, including CV death, with Jardiance compared with placebo when added to standard of care in adults with type 2 diabetes and established CV disease. In a separate analysis, Jardiance was also found to have reduced risk for CV events consistently in groups divided by LDL cholesterol level. //
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United Continued from page 1competition” in the prostacyclin receptor agonist Uptravi (selexipag) from Actelion Ltd., United Therapeutics Inc. CEO Martine Rothblatt said that being able to promote her firm’s therapy for reduction in morbidity and mortality – as well as improvements in exercise, as the label now proclaims – could boost sales.Not everyone is optimistic. H.C. Wainwright analyst Andrew Fein wrote in a June 15 research report that “the impact of Uptravi [is] starting to manifest on Tyvaso [inhaled treprostinil]” sales, as well as those of Silver Springs, Md.-based United’s PAH therapy Remodulin (treprostinil), while Orenitram’s performance in the market has proved “lackluster.” The “scales are tipping the other way,” in his view. “During the last six months, we have struggled with the lack of visibility into the future of United’s PAH franchise. In our last quarterly update, we pointed to the need for smart and sizeable business development as a top corporate priority for the company. Further, in the face of weak sales and an intellectual property portfolio under steady attack, we singled out the company’s share repurchase program as the only driver of near-term value, or rather, savior from near-term value erosion.” Actelion’s Uptravi was approved in late 2015. Analysts forecasted at the time that global sales of Uptravi could reach $1.3 billion annually by 2020 as the therapy takes its place in the Swiss biotech giant Actelion’s PAH portfolio, bracketed by its next-generation endothelin receptor antagonist, Opsumit (macitentan), for baseline treatment and Veletri (epoprostenol for injection) for patients with late-stage disease. (See BioWorld Today, Dec. 23, 2015.)United recently reported first-quarter revenues of $369 million, a 12.7 percent increase over the same period in 2015, citing a $27.3 million increase in net sales of the phosphodiesterase type 5, or PDE5, inhibitor, for PAH drug Adcirca (tadalafil), a $19.3 million increase in net sales of Orenitram, and a $14.2 million increase in net sales of Unituxin (dinutuximab), approved last year to treat children with high-risk neuroblastoma. Remodulin sales dipped by $6.5 million, and falling by $11.2 million was revenue from Tyvaso. The company reported net income of $235.5 million for the quarter, compared to a net loss of $16.6 million for the same period in 2015. Wainwright’s Fein voiced skepticism that the firm will be able to catch up with Actelion in PAH, predicting “a game in which United will be several years behind, when (and if, depending on the magnitude of risk that one assigns to the [FREEDOM-EV study, intended to bolster the wider claims for Orenitram]), a supplemental label finally makes it to a market penetrated by Uptravi. We believe that this head start of several years might just give Uptravi a lead, even when considering the dynamics of physician loyalty.” Doctors who like United “might give Orenitram over Uptravi when presented with a starter choice
between the two, but would they really switch patients from Uptravi to Orenitram once the latter arrives following a few years of stable treatment with the former? We doubt that,” he wrote. The Griphon trial with Uptravi was the largest and longest PAH trial so far and turned up a 40 percent reduction in morbidity/mortality over placebo.
AND HERE COMES BARDOXOLONEUnited CEO Rothblatt, though, speaking during the company’s earnings call, pointed to the package insert for Uptravi. “You will see that after 36 months, a little bit more than half of the patients on Uptravi have at that point still been morbidity/mortality event-free. So in other words, almost half of the patients on Uptravi have suffered a progression of their pulmonary hypertension. And the difference with placebo is not huge; with placebo a little bit less than half the patients are morbidity/mortality event-free after three years. Meaning just a little bit more than that half of the patients suffered an event within those three months. So this just gives you the picture. There is no plateauing; it is just a downward spiral. These drugs are not cures, and patients with pulmonary hypertension, more than 90 percent of them progress to the late stage where drugs such as Orenitram and Tyvaso and Remodulin would be the logical next choices.”Rothblatt made known her confidence that the firm can broaden its presence in PAH, rather than see it shrink, saying “the ship [is] in a good port. We want to continue the business development course of expanding our current drugs in pulmonary hypertension.” Five types of PAH exist, she noted, according to categories established by the World Health Organization (WHO). “All of these drugs that everybody is scrambling for, ourselves included, are in the WHO 1 pulmonary hypertension [category],” she said. “But that leaves literally hundreds of thousands of patients with WHO 2, 3, 4, and 5 pulmonary hypertension as an unaddressed unmet medical need. We would characterize those areas as corridors of indifference. United’s mantra is to identify corridors of indifference, such as category 3 pulmonary hypertension, and run like hell down them. And that is what we are doing with our great Tyvaso product, which is uniquely able to surmount the perfusion-ventilation mismatch issue” in treating PAH, she said.As part of its first-quarter developments, United recorded changes in its management, naming Rothblatt, chairman, as sole CEO after president and co-CEO Roger Jeffs prepared to exit, although he remained a senior advisor to the company. Michael Benkowitz, former executive vice president of organizational development, was appointed president and chief operating officer to replace David Zaccardelli, also leaving the company this month. Analyst Fein wasn’t sold on all that, either. “Overall, we struggle to think of the resignation[s] as retirement[s] (as per the quarterly call). Both had been in these
NDFC Continued from page 1bringing new drugs to market, now there is a place to share their woes and wisdom: the New Drug Founder’s Club, or NDFC for short. Formed six months ago in Suzhou Biobay, the club has already attracted 125 members, who conform to strict guidelines governing who can join. It must be the top decision-maker in organizations that are doing or supporting new drug discovery. Biotech CEOs and co-founders make up the majority, but there are also discovery-focused CRO CEOs, early stage venture capital partners and R&D heads at MNC biopharma. It is a sign of the times that China has the critical mass of senior people working on drug innovation to support such an enterprise. It is not that there is a shortage of life science conferences in China - there are plenty, such as the ChinaBio Partnering Forum, ChinaBio Leadership Retreat, the China Healthcare Investment Conference, the China Trials Summit or the DIA China Drug Discovery Innovation Conference. And there is at least one exclusive club, too: the invitation-only BayHelix. But NDFC is trying to fill its own niche – that it is lonely at the top for those walking the high-risk tightrope of new drug discovery. “There is no other club at this high level,” explained Alex Chen, founder and CEO of Crystal Pharmatech. “When people are at this level, they don’t want to share information so openly in other forums. The idea is to make sure that every member can share information very openly to help each other. It is really about how to help each other using your own resources and own experience.” To ensure the sense of trusted peer group sharing is protected, the club regularly organizes closed-door discussions for up to 40 members. But recently, they held their first annual meeting, a conference that attracted 180 Chinese entrepreneurs, scientists and investors. Many speakers and attendees at the gathering are regular participants in China’s international forums: Peng Wang, CEO of Suzhou Yaobao Pharmaceutical R&D Co. Ltd., welcomed the crowd as NDFC chairman; Michael Liu, CEO of Innovent Biologics Inc., of Suzhou, shared insights on how to best position R&D strategy to maximize product value; and Xueming Qian, chairman and CEO of Mabspace Biosciences Co. Ltd., shared his thoughts on differentiated antibodies. The standard formula is that China’s innovators are also China’s internationally savvy returnees. It usually follows that domestic conferences may have one or two presentations from innovative local companies, but they also include the gamut of China’s life sciences industry, with generics makers taking up the majority of airtime. But at the NDFC conference, the lineup was almost solely devoted to Chinese drug discoverers, including many that do not often make the international circuit such as KBP
Biosciences Co. Ltd., Hemay Medicine Co. Ltd., of Tianjin, and Suzhou Mednas Co. Ltd., to name a few.One exception was an English presentation given by Chinese-American lawyer Brian Sun, partner-in-charge of the Jones Day L.A. office, who gave a sobering presentation on the contentious topic of trade secrets in drug discovery efforts. An especially pertinent topic as more Chinese biopharmas lure top researchers to China from the U.S.He warned scientists to take precautions to protect themselves from the increasingly harsh actions of the U.S. government in persecuting Chinese scientists. That included urging scientists not to be naïve about putting one’s work in a thumb drive when leaving the office and assuming published work won’t get mistaken for a trade secret. Even if the information is in the public realm, overzealous lawyers may be unaware of the details until it is too late. He also advised Chinese companies when hiring returnees from western companies to put in writing that they are not hiring them for their proprietary knowledge, as an added protection. But for most of the session, the room was more upbeat. Many had come to hear industry pioneer Lieming Ding, CEO and chairman of Betta Pharmaceuticals Co. Ltd., talk about how he got one of the first successful novel drugs, Icotinib, a selective, first-generation EGFR tyrosine kinase inhibitor, to market. In 2015, Icotinib achieved ¥2.46 billion (US$371.7 million) in sales and is a top cancer drug, beating out MNC contenders. But that came after lengthy price negotiations with the authorities. According to Ding, the monthly cost of Icotinib (¥11,800) is lower than rivals (gefitinib at ¥16,500 and erlotinib at ¥19,800). He was also keen to mention that to date Betta has given 1.33 million boxes of Icotinib for free, providing a lifetime dose to 30,000 patients valued at ¥3.6 billion.
MONEY, MONEY, EVERYWHERE A real game-changer in 2016 promises to be the amount of capital sloshing around in the system. According to data compiled by Chinabio LLC, there is $13 billion in capital earmarked for life sciences investment in China that venture capital firms have not allocated, and the clock on those VC funds is ticking. With volatility and oversupply rocking many traditionally lucrative sectors of the economy such as construction, investors are eyeing the health care industry favorably and are willing to tackle the risks of discovering new drugs. “We suddenly realized Chinese new drug discovery and development is booming,” said Crystal’s Chen. “In the past, it was hard to get funding, but starting from last year everybody is so interested in the health care industry and developing new drugs, it is becoming more possible. Firstly, we have many experienced people coming back to found companies and focus on new drug discovery and now they can get funding.” That was backed Wenxin Yu, health care analyst with Haitong
See NDFC, page 11
MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 9 OF 14
Frontier Continued from page 1micrometers thick – was designed to overcome safety issues common in prescription-strength painkillers for chronic pain. AB001 is a nonsteroidal anti-inflammatory drug (NSAID) that utilizes a nonhydrogel-based matrix formulation to enhance skin penetration, tissue permeability, anti-inflammation and pain relief potency. Proving the efficacy of new pain medications is a difficult undertaking. Pain is subjective and hard to quantify, while the power of the placebo effect can be tough to tame. Frontier, however, did not shy away from the risk and is confident the results from the phase II trial show that its product is not only effective but also safe. “Demonstrating superior pain relief against placebo is a challenge, especially for [a] patch product; there hasn’t been meaningful innovation in many years. We are very encouraged with these phase II data that strongly demonstrated AB001’s safety and clinical efficacy,” said CJ Wang, CEO of Frontier Biotech. For the FDA-approved phase II trial, 146 study subjects were divided into two equal groups, with one receiving AB001 and the other placebo. Every morning for 14 days, subjects applied two patches to their lower back, wearing the patches for 12 hours. The primary endpoint was a change in pain intensity on the visual analogue scale (VAS) on day 15. AB001 met the primary endpoint, demonstrating statistically significant (p=0.023) and clinically meaningful pain relief against placebo. On average, 75 percent of patients treated with AB001 experienced 34.1 percent reduction in pain from baseline at week two, 50 percent of patients reduced 58.3 percent of pain and 25 percent of patients reduced 78.5 percent of pain. In addition, AB001 achieved statistically significant analgesia against placebo at week one (p=0.024), greater reduction than placebo in the mean Roland-Morris Disability Questionnaire score at week two (p=0.006), and more subjects were satisfied (extremely, very or somewhat) with study medication than that in the placebo group at week one (p=0.035) and week two (p=0.045). Importantly, AB001 performed well in terms of safety. No drug-related serious adverse events were observed. The most common issues were application-site adverse events, which occurred in seven subjects (9.6 percent) in the AB001 group and five subjects (6.9 percent) in the placebo group. Because the medicine goes through the skin, avoiding the digestive system, it is less harmful than orally administered pain meds.“Millions of people in the U.S. suffer from the debilitating effects of chronic low back pain and many have to take oral NSAIDs despite their serious side effects in GI tract and increased risks in cardiovascular diseases,” said Wang. “Our results, in terms of the scale of pain reduction, is relatively equal to the oral cyclooxygenase-2 (COX-2) inhibitors like Bextra or Vioxx [that were recalled due to safety issues]. If you look into the clinical data published by Pfizer [Inc.] and Merck
[& Co. Inc.], the scale of the pain reduction is about the same as ours. It is very exciting that we achieved very significant pain reduction,” he added. In the U.S., there is only one prescription-strength FDA-approved pain patch, the Flector patch (diclofenac epolamine). It is indicated for the topical treatment of acute pain due to minor strains, sprains and contusions. The main side effects can include dryness, itching, peeling or scaling of treated skin. Where the U.S. has only one pain patch on the market, they are ubiquitous in other countries such as Japan and in Europe. Globally, the pain patch market has grown to $7 billion 2015, an increase of $238 million over 2014, according to Kalorama Information. In November 2014, Frontier in-licensed AB001 from Absize Inc., a spinoff company from the University of Osaka, Japan. At that time, Absize founder Isamu Oh joined forces with Frontier, coming on board as vice president of operations. Absize’s technology platform, laser-induced nanolization technology (LINTEC), developed AB001. Oh received his BS in physics from Nanjing University and a doctorate in physics from Osaka University.Frontier has the Greater China rights with the option for global rights for AB001. Frontier is planning to register AB001 in China this year and is looking for partners as well as considering taking it to market on its own. “We plan to bring the CMC and the clinical registration back to China [from the U.S.] this year. The CFDA requires that you have the CMC data before you can file an IND,” said Wang.
MATCHING EFFICACY BUT WINNING ON SAFETY Since Frontier’s founding in 2002, the company has been working on its primary lead candidate, albuvirtide, a long-acting HIV agent in a phase III trial in China with the potential to be approved next year by the CFDA. It is another case of matching industry standards of efficacy but cracking the problem of safety through formulation. (See BioWorld Today, June 6, 2016.)Albuvirtide’s long-acting formula, dosed as a once-weekly injection, promises to provide much-needed relief to patients on a daily regimen of oral drugs that are hard on the body. “Our long-acting injection can help with the viral suppression without taking oral pills; our drug has equal or better efficacy but has safety better than all of the oral pills at this point,” said Wang. Wang said he figures albuvirtide will beat several MNC competitors, which are only in phase II trials. “After the initial 14 years of hard work, we are now getting to the next stage. Our product is about to come out and we are facing a huge opportunity,” said Wang. “Frontier is positioned to be one of the leading research-based drug developers in China and going global.”The company has two subsidiaries: Chongqing Frontier Biotech, for discovery and early development, and Beijing Frontier Biotech, for clinical, regulatory and government affairs. //
Diagnostics Continued from page 3Geneweave’s Smarticles technology is designed to identify multidrug-resistant organisms quickly and assess antibiotic susceptibility directly from clinical samples. It consists of DNA-delivery bioparticles and custom-designed DNA molecules that cause live bacteria to produce light. They are engineered to target a family, genus or species of bacteria.
EMERGING TECHNOLOGIES FACING HURDLESStill, some companies are looking beyond culture and PCR. However, even with new tests, the reimbursement hurdle is a tough one to surmount, as obtaining a new code can prove to be a time-consuming and challenging process. In addition, many of those emerging technologies only can identify a limited set of pathogens. And while the identification process takes less than an hour, susceptibility tests may have to run separately.Emerging technologies include matrix-assisted laser desorption ionization-time of flight (MALDI-TOF), through which results are available in less than an hour. While the cost-per-test is negligible, instruments run more than $200,000.One company using MALDI-TOF is Billerica, Mass.-based Bruker Corp., with its FLEX series. At the American Society for Microbiology (ASM) Microbe 2016 conference earlier this month, Bruker reported on a collaboration with the Special Bacteriology Reference Laboratory at the U.S. Centers for Disease Control and Prevention to create an expanded microorganism reference library for the Bruker MALDI Biotyper. The MALDI Biotyper library contains spectra for more than 2,300 species of bacteria and fungi, according to the company.Another emerging technology is next-generation sequencing, which yields results within one to two days at a cost of more than $100 per test. Still, as Norman Moore, director of Scientific Affairs, Infectious Disease at Waltham, Mass.-based Alere Inc., told BioWorld Today, diagnostic companies can’t do it alone; it is essential to make all stakeholders, including doctors and patients, aware of the potential harms of overprescribing. With that, tests need to be sensitive and “fast enough to change prescribing habits,” Moore added.
A HOST OF COMPANIES IN THE FRAYOther companies have recognized that point. In January, a number of drugmakers and other stakeholders pledged to help in the fight against antibiotic resistance. Joining the ranks were a number of diagnostics companies that also vowed to help in the fight.The signatories were a multinational group – Alere Inc., Biomérieux SA, Cepheid, Curetis AG, F. Hoffman-La Roche Ltd., Hemocue AB, Hyrax Biosciences (Pty) Ltd., Mobidiag Oy Ltd., Momentum Bioscience Ltd., Quantumdx Ltd. and Spectromics.Many of those that signed the pledge touched on what is viewed as the biggest problem facing patients: the time it takes
to determine treatment regimen. Oliver Schacht, CEO of Curetis, told BioWorld Today that his company is looking to make faster tests a reality. Curetis has made “tremendous progress in the first half of 2016” and is eyeing the launch of its intra-abdominal infection cartridge in Europe, following the expected fourth quarter completion of clinical validation. “That panel will most likely also include the antibiotic resistance marker associated with the Colistin resistance in E. coli that was at the core of the recent patient case in the U.S.,” he said.Curetis GmbH is the operational subsidiary of Curetis NV, with its headquarters in Holzgerlingen, Germany. The company expects to establish a U.S. operation in the second half of the year and hopes to announce where it will set up shop shortly, Schacht said.Simon Travers, managing director at South Africa-based Hyrax Biosciences, confirmed that his company is working on a number of AMR-related products. “Our next product will be a tool that enables the analysis of sequence data from TB – analyzing either full genome sequences or sequence data generated by targeting specific regions of the genome – that is capable of accurately detecting resistance to all of the currently available TB drugs,” he told BioWorld Today.In addition, Hyrax has developed a similar tool for Staphylococcus aureus and is expanding its product line to focus on other bacteria.Travers said his company also is developing databases and analytics tools with a goal of real-time surveillance of infections and resistance at a local, national and international level. ”While this will be applicable on a global scale, it will be particularly pertinent for resource-limited settings where our knowledge of the prevalence of antimicrobial resistance is limited,” he added.Formed in 2014, Manchester, U.K.-based Spectromics is working on a rapid test for guiding the use of antibiotics for routine urinary tract infections (UTIs) in the community.CEO Neil Butler told BioWorld Today that UTIs may not be viewed as severe as sepsis or kidney infections. However, roughly 25 percent of sepsis cases originate from UTIs, resulting in kidney infections that can pass into the bloodstream. “Once a patient has sepsis, survival rates are poor, 50 percent or less, and hence better to treat before it becomes a kidney infection,” he added.Butler added that he also sits on the board of U.K.-based Atlas Genetics Ltd., which is developing rapid molecular diagnostic tests for sexually transmitted diseases. The company is developing a test for drug-resistant-gonorrhea.
MORE INTELLIGENT ANTIBIOTIC USELocated in Newcastle, U.K., Quantummdx is preparing for the launch of its Q-POC technology in 2018. According to company spokeswoman Lucy Harvey, Q-POC will provide sample-to-result testing in roughly 10 to 20 minutes. “Q-POC
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MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 11 OF 14
Diagnostics Continued from page 10will identify the presence and strain of infection, ensuring the right drug is prescribed the first time,” said Harvey, who added that the ultimate goal is to facilitate “a more intelligent use of antibiotics.” To that end, globally distributed Q-POC devices will allow for geotagging and the anonymization of pathogen data, which would then be sent to the cloud for real-time disease and drug-resistance monitoring, rapid detection and pathogen containment. “[T]he data could also be used by public health bodies to allocate resources effectively. We call this system The Internet of Life,” Harvey told BioWorld Today.Indeed, to Kevin Krenitsky, president of Opgen Inc., the field of infectious disease has been “languishing in antiquity,” particularly with traditional methods taking days to identify antibiotic resistance.Although it did not sign the January letter, Gaithersburg, Md.-based Opgen is looking to unveil what Krenitsky has dubbed “very disruptive platform technology,” incorporating bioinformatics and “attack[ing] the problem from multiple angles.”The company wants to decrease the time it takes to treat patients with a one-hour test. “What’s important here is not the
pathogen; it’s the resistance within the pathogen,” he said in early June 2016 during the LD Micro Invitation in Los Angeles. With that in mind, the company is looking to leverage its bioinformatics database and rapid array test to inform patient treatment. The company’s goal is to have information about a patient sample back within an hour, including pathogens and resistance genes. The results could be evaluated using the company’s Acuitas Lighthouse database, which would reveal the organism causing the disease, as well as the antibiotic resistant genes and the type of treatment regimen that would be most appropriate. Not only could that technology help a single patient with the appropriate treatment, according to Krenitsky, but it could also prevent the spread of an infection throughout a hospital with timely identification of a pathogen.The company unveiled data at AMS Microbe 2016 in Boston demonstrating how its Acuitas Resistome Test can be used in epidemiological studies to aid in routine evaluations for mechanisms of resistance in carbapenem resistant Enterobacteriaceae.The test is intended to detect antibiotic resistance genes associated with Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae and Citrobacter freundii. //
Securities. “Innovative new drug development is getting a big push, supported by investment and the CFDA regulations. From 2015, getting investment for innovative drugs is much easier than anytime in the past 10 years. Taking a historical perspective, China’s new drug industry is on the eve of its big break. The pity is we don’t have any really big, innovative drug company on China’s A-share market.” The industry has also been emboldened by the success of big-ticket deals between Chinese companies and foreign firms, providing a new path to revenue viability. “After 2015, the understanding of the capital market changed,” she said. “Before, it was thought, a company needs to launch a new drug to get revenue. But from 2015, we found that companies with overseas patent license can get advance revenue. “The biggest examples of this was seen when Beigene and Hutchison Medipharma both went public on the Nasdaq.” //
NDFC Continued from page 8
OTHER NEWS TO NOTE
Teva Pharmaceutical Industries Ltd., of Jerusalem, said the EMA’s Committee for Medicinal Products for Human Use issued a positive opinion recommending marketing authorization for Cinqaero (reslizumab), a humanized interleukin-5 antagonist monoclonal antibody, for add-on therapy in adult patients with severe eosinophilic asthma inadequately controlled despite
high-dose inhaled corticosteroids plus another medicinal product for maintenance treatment. The opinion is based on efficacy and safety data from five placebo-controlled studies in 1,028 adult and adolescent asthma patients treated with reslizumab 3 mg/kg. The recommendation will now be reviewed by the European Commission, where a final decision on the authorization is expected in the second half of 2016.Zymeworks Inc., of Vancouver, British Columbia, said it entered a research collaboration with the University of Victoria and the BC Cancer Agency to develop engineered cytokine and cytokine receptor pairs. Under the terms, the collaborators will engineer variant forms of cytokine-receptor complexes to allow precise control of cellular signaling events. Engineered cytokine-receptor pairs will be designed using Zymeworks’ Zymecad protein modeling and engineering technology, and further characterized at the University of Victoria and the BC Cancer Agency.
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Bionomics Ltd., of Adelaide, Australia, completed enrollment in its U.K.-based phase II trial of BNC210 in generalized anxiety disorder. The double-blinded, placebo and lorazepam-controlled, four-way crossover single-center study involves patients with untreated disease. and will evaluate the capacity of BNC210 to engage brain systems relevant to anxiety. Endpoints include both significant changes in cerebral perfusion using arterial spin labeling and in emotional task-related brain activity using the emotional faces task during functional magnetic resonance imaging. BNC210 is an orally administered negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor.Immuron Ltd., of Melbourne, Australia, said its IMM-124E phase II trial for the treatment of non-alcoholic steatohepatitis has reached its 50 percent recruitment milestone with 56 patients having been randomized and an additional four patients to be randomized last week. To date, 25 patients have completed treatment. No adverse events have been reported. The drug is composed of anti-lipopolysaccharide antibodies and adjuvants, many of which are glycosphingolipids, targeting the gut microbiome and the innate immune system of the gut, the company said.Kitov Pharmaceuticals Holdings Ltd., of Tel Aviv, Israel, reported data from its phase III study of KIT-302, which comprises two approved drugs, celecoxib and amlodipine
besylate, and is designed to simultaneously treat osteoarthritis pain and hypertension. Further analysis of data from the trial, whose positive top-line results were announced in December 2015, showed that celecoxib increased serum creatinine compared to placebo; impaired renal function is a major concern with nonsteroidal anti-inflammatory drugs. In contrast, while amlodipine alone reduced serum creatinine (-2.55 umol/L), a greater reduction in plasma levels of creatinine was achieved in patients in the KIT-302 arm (-3.22 umol/L), suggesting better renal function. Additional data measuring peripheral edema, a known side effect of calcium channel blockers such as amlodipine, showed that peripheral edema was reported in 15.6 percent of patients receiving amlodipine vs. 8.2 percent of patients receiving KIT-302. (See BioWorld Today, Dec. 16, 2015.)Neurotrope Inc., of Newark, N.J., said a study published in the Journal of Biological Chemistry shows that its lead Alzheimer’s disease (AD) drug, bryostatin, licensed from the Blanchette Rockefeller Neurosciences Institute, increases the levels of the synaptic scaffolding protein PSD-95 and induces the movement of phosphorylated PSD-95 to the neuronal membranes. The study showed that bryostatin induced activation of PKC epsilon increased synaptic number, presynaptic vesicle density and clusters of PSD-95. It is known that either amyloid beta or tau, both toxic proteins in AD brains, can induce reduction of PSD-95 in excitatory synapses in the hippocampus, the company noted. That PSD-95 reduction continues to occur as the AD pathologies advance. A phase IIb trial is under way.
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MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 13 OF 14
Infection Continued from page 4Cleaning those devices after they have been inside of a patient is no easy task. Gerrans likened it to trying to get burnt cheese off a frying pan. Fluid tends to cook, or burn, inside the operating channel of endoscopes during a procedure and if those sticky spots are not completely cleaned off before it will inevitably slough off into the next patient, he said.The idea behind Patient Safe’s technology is that the visual inspection it provides will prompt hospital staff to do a better job cleaning the scopes before an infection spreads.The Steriview was born from another company Gerrans leads, Sanovas Inc., which initially developed the small diameter scopes as a means of going deep into a patient’s lungs to diagnose and treat disease.The technology has been on the market as an infection control system for about a year and the uptake has been quite positive, Gerrans said. In a recently published study, the device found 613 out of 860 inspected instruments to be dirty. That study included endoscopes as well as other laparoscopic devices and tubes.In addition to infection control, Gerrans said Patient Safe’s technology also helps hospitals inspect the integrity of those devices, which are also prone to nicks and scratches that can rust out over time or provide a breeding ground for bacteria.It’s really a multifaceted problem, Stephen Schimpff, Patient Safe’s chairman, told BioWorld Today. Schimpff, the retired CEO of the University of Maryland Medical Center, spent the bulk of his medical career researching the causes, prevention and treatment of infections in cancer patients undergoing chemotherapy. The first challenge with device-related infection control is being able to see the contaminated parts of an endoscope or other device. The next problem is figuring out how to get the bacteria or residual biomaterial out without damaging the device.“It turns out, in some cases, you can’t just put a scope brush down there or a piece of steel wool because you’re going to damage the inside of the scope,” Schimpff said. “It’s a pickle.”
THERE’S AN APP FOR THATIn an age where mobile apps are a regular part of daily living, it’s not too surprising that there is an app designed to track an endoscope through each step of the cleaning and sterilization process. What is surprising, perhaps, is the fact that such an app wasn’t on the market sooner.Philadelphia-based Prairie Dog Tech LLC launched the Pd-vision in June as an optional enhancement to its previously released infection control app called The Observer. Together, the apps are designed to help hospital staff document the process of disinfecting reusable scopes by creating a database of images that can be searched by time and date, or scope ID.Prairie Dog Tech’s founding member, David Bassion Jr., told BioWorld Today that the idea for a Bluetooth-based endoscope
tracking system came from walking around at an endoscopy convention last year and noticing that there were a lot of tracking systems on the market, but most – if not all – of the existing systems relied on information manually recorded by a clinician.Bassion’s team decided to create a tracking system that truthfully tracks the scope through each step of the sterilization process and alerts the staff of potential problems.“We want everyone to know everything,” Bassion said.
OPGEN LIGHTS THE WAYOpgen Inc. offers a multidrug-resistant organism (MDRO) management system, the Acuitas Lighthouse, that helps hospitals navigate infection control issues.Kevin Krenitsky, president of Opgen, told BioWorld Today the cloud-based Lighthouse system leverages the company’s bioinformatics analytics software to track and prevent the spread of infection from the time an infectious patient enters the hospital. Hospitals can use the system in conjunction with Opgen’s rapid MDRO gene test to screen patients for superbugs and other infections, like Clostridium difficile, as soon as they walk through the door.The Lighthouse system not only helps hospitals track the location of threats but guides preventative actions to nip infections in the bud before they spread.
SEND IN THE ROBOTSGerm-zapping robots that use ultraviolet (UV) light to disinfect hospital rooms grabbed attention a couple of years ago in the wake of the Ebola epidemic. In 2014, San Antonio, Texas-based Xenex Disinfection Services LLC offered its UV robots to Emory University and the CDC to disinfect the rooms where U.S. Ebola patients were treated and the airplanes that transported those patients. The Xenex robot is a portable system designed to penetrate the cell walls of microorganisms, including bacteria, viruses, mold, fungus and spores, destroying all the superbugs and pathogens that could be lurking in a hospital room – the operating room or the emergency room – in five to 10 minutes. The robot is operated by hospital housekeeping staff. After cleaning the room first through traditional methods, the robot is rolled in as an added layer of patient safety, disinfecting high-touch surfaces and difficult-to-clean nooks and crannies. The company launched the first version of its robot in 2010 and a new version of the robot in late 2013.According to the company, the Xenex robot is powered by xenon, an environmentally friendly gas, instead of mercury, which is what most of the competing systems on the market use. In addition to being toxic, mercury-based UV robots only operate in one spectrum and can take hours to disinfect a single room, Xenex said. Yet, according to one of such competitor, Tru-d SmartUVC LLC, of Gaithersburg, Md., the fear around mercury is a misconception.Tru-d bulbs use ultra-low levels of mercury vapor that are
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MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY PAGE 14 OF 14
Infection Continued from page 13consistent with modern fluorescent and compact fluorescent bulbs found throughout virtually every U.S. hospital that are endorsed by the Environmental Protection Agency and the Department of Energy. No mercury byproduct is emitted by the bulbs either, CEO Chuck Dunn said.Until recently, Tru-d’s biggest adoption barrier was a lack of evidence showing a direct correlation between the elimination of MDROs and the reduction of infections throughout a facility using no-touch disinfection technology. The randomized BETR-D study (Benefits of Enhanced Terminal Room Disinfection), funded by the CDC, eased those concerns, Dunn said.BETR-D compared four methods of terminal room-cleaning strategies at nine hospitals over 22,000 patient days. The researchers found that Tru-d reduced the cumulative number of hospital-acquired infections by about 30 percent for patients who stay in rooms previously occupied by an infected patient.Dunn told BioWorld Today that the company’s Sensor360 technology sets Tru-d apart from its peers in the UV disinfection space. The technology measures the amount of UV energy that is reflected back to the robot, he said, enabling it to overcome room variables such as size, shape and contents to deliver the precise, lethal dose of UVC light needed. Tru-d touts that its device kills up to 99.9 percent of pathogens in a room from a single position with a single cycle of UV energy. //
new roles for less than 16 months, during a pivotal time for the company, while personnel continuity had not really been in question prior to their promotion.” He conceded that he had “no insight into the company’s power dynamics, our best guess would be that the shake-up is related to likely divergence in strategic vision for the company.” In his opinion, “all the elements for a potential clash were in place,” given “a successful founder and CEO that potentially still views the company as committed to the one original mission (and who, by now, is likely not driven by financial incentives) vs. a long-time icon of the same company finally promoted to co-captain, with a proven interest in expanding into non-pulmonary orphan pediatric indications.” Calling the company “at a crossroads, where transformative business development may be the only path to long-term value,” he said the “hypothetical internal dynamics matter significantly.”Meanwhile, the PAH treatment approach itself may be transforming. Enter Irving, Texas-based Reata Pharmaceuticals Inc., shares of which late last month climbed 18.8 percent to $13.07 from an IPO pricing of $11. The sale of 5.5 million shares raised net proceeds of $52.5 million. Funds in hand, initially hoped to total as much as $64 million, will be used to advance
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Reata’s lead antioxidant inflammation modulator bardoxolone through a phase III trial and additional phase II programs. (See BioWorld Today, May 27, 2016.)Bardoxolone, which targets the underlying PAH disease processes of oxidative stress, mitochondrial dysfunction and chronic inflammation/fibrosis, has yielded phase II data suggesting “a differentiated clinical profile vs. current vasodilation-based standard of care to establish a new treatment paradigm and drive $1.1 billion in peak U.S. sales,” estimated Piper Jaffray analyst Charles Duncan in a June 20 research report. “Specifically, this profile includes improved safety and tolerability, additive benefits when used in combination with approved options, and notable efficacy in poor-prognosis, connective tissue disease-associated PAH.” Duncan began coverage of Reata with an “overweight” rating and a price target of $22. Shares of the company (NASDAQ:RETA) have been trading at around $20 and closed Friday at $20.14. //
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BENCH PRESSBioWorld looks at translational medicine By Anette Breindl, Senior Science Editor
MONDAY, JUNE 27, 2016 BIOWORLD™ TODAY EXTRA PAGE 1 OF 1
So easy, a baby can do itResearchers have isolated a broadly neutralizing antibody (bnAb) to HIV from an infant who had been infected for roughly a year, showing that bnAbs can in principle develop more rapidly than they usually do. In adults, bnAbs usually take several years to develop because they need to go through multiple steps to do so, a process known as affi nity maturation. In infants, broad neutralization can occur more quickly. The authors identifi ed 10 antibodies in an infant that collectively showed broadly neutralizing activity in plasma. “Characterizing bnAbs that develop early in natural infection will be important to help design vaccine strategies to elicit these antibodies over a shorter period of time,” the authors, from the Fred Hutchison cancer research center, wrote. The antibodies they have identifi ed suggest that “HIV-1-specifi c neutralization breadth can develop without the requirement for several years of antibody affi nity maturation. Moreover, they suggest that infants may provide unique insights into optimal pathways to develop HIV-1-specifi c bnAbs.” They published their fi ndings in the June 23, 2016, issue of Cell.
Organoids predict response to CF drugs
Cystic fi brosis is always caused by mutations in the cystic fi brosis transmembrane conductance regulator (CFTR) gene, but almost 2,000 different mutations in the gene have been identifi ed, and for patients bearing the majority of them, it is unclear whether they will respond to the CF drugs Kalydeco (ivacaftor, Vertex Pharmaceuticals Inc.) or Orkambi (ivacaftor/lumacaftor, Vertex Inc.), and for patients with rare mutations, clinical trials to determine the response are unrealistic. The authors generated rectal organoids from patients with rare CFTR mutations and showed that they could be used to predict the patient response to both Kalydeco and Orkambi. “These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefi t from CFTR-correcting treatment, independent of their CFTR mutation,” wrote the authors, who are at the Dutch University Medical Center of Utrecht. Their work appeared in the June 22, 2016, issue of Science Translational Medicine.
TB-specifi c inhibitor of shared enzyme
A key metabolic enzyme that is shared between Mycobacterium tuberculosis and humans can be selectively inhibited in the bacterium despite the fact that its active site is identical in both. Many metabolic enzymes would make excellent drug targets for antibacterials in the sense that they are critical for bacterial survival, but are poor drug targets because they are shared between bacteria and humans. In their work, the authors
screened small molecules and identifi ed an inhibitor of a key M. tuberculosis metabolic enzyme that does not bind in the active site itself, but at a different site on the enzyme, leading to shape changes that prevented the enzyme from binding its substrate. “Our results demonstrate the selective inhibition of a highly conserved metabolic enzyme that contains identical active site residues in both the host and the pathogen,” the authors from the National Center for Advancing Translational Sciences concluded. Their work appeared in the June 20, 2016, online issue of the Proceedings of the National Academy of Sciences.
Combination treatment takes on KRAS
In cell culture and animal models, combined inhibition of two signaling pathways inhibited the growth of KRAS-mutant lung and pancreatic cancers, but had no effect on KRAS-mutant colorectal cancers. KRAS is one of the most frequently mutated oncogenes, and directly targeting it has proved unsuccessful to date. Inhibition of downstream signaling nodes can temporarily fi ght KRAS-driven cancers, but tumor cells react by up-regulating compensatory pathways. In their experiments, the authors showed that treatment with the MAP kinase pathway inhibitor Mekinist (trametinib, Glaxosmithkline plc.) produced compensatory up-regulation of fi broblast grow factor receptor 1 (FGFR1), and inhibiting both simultaneously could restore the sensitivity of lung and pancreatic cancers to Mekinist in preclinical models. “These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer, the authors from Memorial Sloan-Kettering Cancer Center concluded. Their work appeared in the June 23, 2016, issue of Nature.
Nanoparticles induce immune tolerance
Tolerogenic nanoparticles could suppress type 1 diabetes when administered to mice, providing a path to reversing autoimmunity that is simpler than cell therapy. Type 1 diabetes is an autoimmune disease, and attempts to reverse it by transplanting either regulatory T cells or dendritic cells that can induce regulatory T cells are being tested in clinical trials. In their experiments, the authors treated the animals with nanoparticles that delivered both a type 1 diabetes antigen, and a molecule that activated the aryl hydrocarbon receptor, which promotes immune tolerance. Treatment suppressed autoimmune diabetes. “These data suggest that NPs constitute a potential tool to reestablish tolerance in T1D and potentially other autoimmune disorders,” the authors from Brigham & Women’s Hospital concluded. Their work appeared in the June 22, 2016, issue of Science Translational Medicine.
Anti-Microbial Resistance
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Rapid point-of-care tests for anti-microbial resistanceBy Shyama Gosh, Incidence and Prevalence Database Editor
Antibiotic resistance among microbial pathogens has increased significantly, and the WHO recognizes this to be a major threat to human health. The following figure projects the estimated number of patient deaths due to antimicrobial resistance every year by 2050:
THE CASE OF COLISTINThe antibiotic colistin is reserved for clinical cases where most of all other antibiotics have failed. The mcr-1 gene confers bacterial resistance to colistin in both animals and human beings and there is the fear of possible transmission of mcr-1-harboring Escherichia coli between companion animals and humans. Now, the recent reporting of a first clinical case of colistin resistance in the U.S., together with evidence from Asia (China, Malaysia, Vietnam), Europe (Italy, Germany, the Netherlands, Denmark, Switzerland, Belgium), and Africa stresses the need for continued surveillance for mcr-1 gene frequency worldwide. Colistin use in animals and particularly in pig production has been singled out as responsible for the emergence of colistin resistance. Screening of rectal swabs collected during 2011–12 in Belgium from post-weaning diarrhea in pigs found a 13.2 percent (7/53) prevalence of colistin resistance. Investigators realize the need to find alternative antibiotics, so as to preserve the effectiveness of colistin for the treatment of multi-drug-resistant gram-negative bacteria infections in human medicine. Rapid point-of-care test platforms are designed to be fast and effective diagnostics aimed at identifying microbial infections. Investigators are questioning the adequacy of current day diagnostic technology, as well as the expense, speed,
availability and novelty of this pipeline. While diagnosing an infection, terms such as biomarkers, point of care and speed need to be well defined. Is the biomarker a microbial marker, a pathological marker for establishing diagnosis, or used to track therapeutic intervention? Does the presence of DNA in a sample reflect infection? Where is the point of care? Is it at the physician’s office, at the central lab in a hospital, or in the field? How rapid is rapid? 24 hours? 4 hours? 2 hours? 2 minutes?
THE BELGIUM SCENARIODriven by the inappropriate use of ineffective antibiotics, this section focuses on the status of antimicrobial resistance (AMR) in Belgium. Faced with the challenge of AMR in the country, extensive research is ongoing to develop rapid point-of-care test platforms for blood stream infections, lower respiratory tract infections (LRTI, including community-acquired pneumonia [CAP] and ventilator-associated pneumonia [VAP], and tuberculosis [TB]). Antimicrobial research in Belgium is spread over 5 universities in Flanders. Herman Goossens is Professor of Microbiology at the University of Antwerp and Director of the Dept. of Clinical Pathology at the University Hospital, Antwerp. Holding several expert positions in Belgium, the EU, The U.S., and the WHO, Goossens was elected chair of the Scientific Advisory Board of the Joint Programming Initiative on Antimicrobial Resistance and he is the initiator of the annual European Antibiotic Awareness Day.
RAPP-IDGoosens is the academic coordinator of the RAPP-ID (Development of RApid Point-of-Care test Platforms for Infectious Diseases) project (www.rapp-id.eu), which was initiated in 2011, and is coordinated by Jorge Villacian (Janssen
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Research & Development, Beerse, Belgium), with other member companies including GlaxoSmithKline R&D, U.K., Merck, U.S., Novartis Vaccines and Diagnosis Srl, Italy, and Sanofi-Aventis R&D, France. Since available technology and diagnostic methods often take at least 2 days to produce results, the RAPP-ID aims to develop Point-of-Care Tests (POCTs) for the rapid detection of bacteria, mycobacteria, fungi, as well as viruses and host biomarkers by combining novel specific probes, novel methods of sample preparation, and demonstrating ultra-high sensitive detection methods in hospital patients in less than 2 hours and for outpatients in less than 30 minutes. The platforms will also determine resistance to antimicrobial drugs and will focus on pathogens and host biomarkers involved in blood stream infections, LRTI, including CAP and VAP, and TB.
RAPID DIAGNOSTIC TESTSRapid diagnostic tests that have been developed include those based on immunochromatographic tests (e.g. HIV, hepatitis C, syphilis) and target amplification techniques (e.g., polymerase chain replication [PCR], transcription-mediated amplification, recombinase polymerase amplification, helicase-dependent amplification, isothermal amplification). The Genexpert system (Cepheid) is a platform developed for testing for multiple diseases (TB and rifampicin resistance, HIV viral load, Chlamydia trachomatis, Neisseria gonorrhea) based on real-time PCR, giving results in under 2 hours. One disadvantage of molecular-based tests is that the presence of DNA in a sample from a particular pathogen does not necessarily mean that the patient is suffering from an active infection due to the presence of that organism. Some pathogens are also present in the normal flora but do not cause the host any symptoms.Rapid diagnostic tests are necessary for respiratory tract infections (RTIs) as there is an immediate clinical need to distinguish between bacterial and viral infections and also to rapidly detect drug resistance profiles. Acute cough is the most common reason for antibiotics being prescribed in the community - however, only about 20 percent of acute cough cases are bacterial, thus resulting in antibiotics overuse. Empirical broad-spectrum antibiotic treatment is associated with increased mortality. In patients with VAP, delayed or inappropriate therapy (due to resistance) results in increased mortality. The Influenza POCT is being developed as a patient-friendly, rapid qualitative test to detect influenza virus in a breath sample within minutes after sampling, together with improved sensitivity compared with commercially available assays. The CA-LRTI POCT (rapid qualitative test) differentiates bacterial pathogens during a RTI, within minutes after sampling. The test will identify the most important pathogens, enabling appropriate antibiotic treatment. The Theraedge project (funded under the 7th EU Framework Program for Research and technological development), developed a bacterial lysis and DNA purification protocol on a prototypal microfluidic chip to use in an assay for CA-LRTIs. The GRACE
project (funded under the 6th EU Framework Program for Research and technological development), compared the number of Streptococcus pneumoniae DNA copies detected by PCR, between patients with CA-LRTIs and healthy controls.
CHALLENGESChallenges in developing rapid diagnostics for RTIs include the correct selection of the clinical specimen to be collected and how to collect it; the choice of pathogen(s) to be detected; and distinguishing colonization from infection. S. pneumoniae, Hemophilus influenzae and Moraxella catarrhalis can cause CA-LRTIs but can also be present in the flora of asymptomatic carriers, therefore cut-offs between colonization and infection need to be experimentally delineated. Another challenge is sample preparation, which represents a major bottleneck in developing POCTs. Macroscale lab tests are laborious and can take a few hours, reagents are often refrigerated or frozen, large sample volumes are required and specialized equipment such as centrifuges and bead beaters are used. Rapid POCTs should use reagents stable at room temperature, microliter volumes and the results should be ready in minutes. The nucleic acid based VAP POCT (rapid [less than 2 hours] highly multiplexed POCT) detects key pathogens and associated antibiotic resistance markers for VAP. The cartridge-based platform allows the fully automated, hands-off processing of endotracheal aspirates, while the padlock probes make the assay highly flexible with regard to the addition of additional targets.DNA sequence-based techniques as rapid tests for AMR hold promise, yet some pose limitations. DNA sequencing can predict known resistance, but there is scepticism about it predicting susceptibility. On the other hand, culture-based methods are slower but have the advantage of being able to detect new resistance and to recognize susceptibility. Targeted antibiotic treatment avoids the use of highly toxic last-line and less efficient drugs, reduces mortality among patients and also benefits the clinicians who can develop algorithms
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for better diagnosis and tailor-made antibiotic treatment. Improved infection control will result in health care facilities encountering reduced transmission of multi-drug resistant organisms, whereas the use of such rapid diagnostics by the pharmaceutical industry will reduce the number of patients, time for enrollment and costs of development via the optimal identification of patients that are eligible for the study.Overall, a need exists for point-of-care technologies in primary care in Belgium. A variety of multi-faceted interventions combining physician, patient and public education may successfully reduce inappropriate antibiotic prescription in this country.
Global Burden of Anti-Microbial Resistance - Epidemiology data from the Incidence and Prevalence DatabaseIn the United States, antibiotic resistance has been blamed for at least 2 million illnesses and 23,000 deaths annually. 30 percent-50 percent of antibiotics prescribed in hospitals are unnecessary or incorrect, contributing to antibiotic resistance. The Incidence and Prevalence Database (IPD) of Thomson Reuters reviews the burden of antimicrobial resistance worldwide. The IPD summarized U.S. data from the Antibiotic Resistance Patient Safety Atlas reported by 4,403 health care facilities to the CDC’s National Health care Safety Network (NHSN) during 2011-2014. The summary metrics produced by this Atlas reflected the health care-associated infections (HAIs) and reported on the percent of bacteria causing the HAI that were resistant to a specific antibiotic (percent resistant).
ANTIBIOTIC-RESISTANT BACTERIA CAUSING HAI IN U.S.Among the U.S. states, the percent of bacteria causing health care-associated infections were reported as follows: Enterobacteriaceae resistant to carbapenems (CRE), 0 percent–27.9 percent (3.5 percent nationally); Staphylococcus aureus resistant to methicillin (MRSA), 32.5 percent–67.8 percent (46.4 percent nationally); Pseudomonas aeruginosa resistant to antibiotics in at least 3 categories (multidrug-resistant P. aeruginosa), 3.1 percent–46.9 percent (14.2 percent nationally); Acinetobacter resistant to antibiotics in at least 3 categories (multidrug-resistant Acinetobacter), 5.0 percent–88.1 percent (54.8 percent nationally); Enterobacteriaceae resistant to extended-spectrum cephalosporins (indicative of extended-spectrum beta–lactamase presence) (E. coli, 0 percent–24.4 percent [13.4 percent nationally], Klebsiella spp., 0percent–73.0 percent [20.0 percent nationally], Enterobacter spp., 15.0 percent–43.2 percent [28.5 percent nationally]); Enterococcus resistant to vancomycin (vancomycin-resistant Enterococcus spp. [VRE]) (E. faecium, 38.5 percent–86.5 percent [77.3 percent nationally], E. faecalis, 0 percent–17.8 percent [6.9 percent nationally]); Staphylococcus aureus resistant to methicillin (MRSA) and additional antibiotics suggesting origin in the community
(community-associated MRSA), 10.0 percent–55.5 percent [31.2 percent national resistance]); Staphylococcus aureus resistant to methicillin (MRSA) and additional antibiotics commonly used to treat MRSA (linezolid, 0.7 percent; daptomycin, 1.3 percent; or intermediate/ resistance to vancomycin, 0.2percent); E. coli resistant to fluoroquinolone (a commonly prescribed class of antibiotics for infections thought to be caused by E.coli and related organisms), 12.1 percent–50.5 percent (33.0 percent national resistance); P. aeruginosa resistant to piperacillin/tazobactam, 0 percent–41.7 percent (10.0 percent national resistance).
HEALTH CARE-ASSOCIATED INFECTIONS IN EUROPEThe IPD also reported corresponding data from the European Center for Disease Prevention and Control. The Annual Epidemiological Report 2013 gave an overview of the epidemiology of communicable diseases of public health significance in Europe, drawn from surveillance information from countries on the communicable diseases and health issues for which surveillance is required in the European Union (EU) and European Economic Area (EEA) countries. Surveillance systems capture only a proportion of the cases actually occurring: some cases of disease remain undiagnosed (under-ascertainment), and some are diagnosed but not reported to public health authorities (underreporting). The pattern of this under-ascertainment and underreporting varies by disease and country, being a complex mix of health care-seeking behavior, access to health services, availability and use of diagnostic services, reporting practices by doctors and others, and the operation of the surveillance system itself. For these reasons the direct comparison of disease rates between countries should be undertaken with caution.In 2011-2012, 29 EU/EEA Member States and Croatia participated in the first EU-wide, European Center for Disease Prevention and Control (ECDC)-coordinated point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals. ECDC received data for a total of 273,753 patients in 1149 hospitals. Of these, 231,459 patients from 947 hospitals were included in the final European sample for analysis.
PREVALENCE OF INFECTIONS IN EUROPEThe prevalence of patients with at least one health care-associated infection in acute care hospitals in the PPS sample was 6.0 percent (country range: 2.3 percent to 10.8 percent). When extrapolated to the average daily number of occupied beds per country, the health care-associated infection prevalence was estimated at 5.7 percent. The number of patients with at least one health care-associated infection on any given day in European acute care hospitals was estimated at 81,089. The annual number of patients with at least one health care-associated infection in European acute care hospitals was estimated at 3.2 million.Of a total of 15,000 reported health care-associated infections, the most frequently reported types of health care-associated
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ExplorE thE IncIdence & Prevalence database: thE most EfficiEnt way to look at thE world’s EpidEmiology data
infections were respiratory tract infections (pneumonia and lower respiratory tract, 19.4 percent and 4.1 percent, respectively), surgical site infections (SSIs; 19.6 percent), urinary tract infections (19.0 percent), bloodstream infections (10.7 percent) and gastrointestinal infections (7.7 percent). Health care-associated infection prevalence was the highest in patients admitted to intensive care units, where 19.5 percent patients had at least one health care-associated infection, compared with 5.2 percent on average for all other specialties combined. 23 percent of health care-associated infections were present on admission. One-third of health care-associated infections on admission were SSIs.
SURGICAL SITE INFECTIONS IN EUROPEIn 2011, 16 countries participated in the surveillance of SSIs according to the ECDC HAI-Net SSI protocol. Three countries submitted data on SSIs for the first time in 2011. A total of 424,871 surgical operations were included and a total of 8,371 SSIs were reported. Approximately half of all SSIs were reported after patient discharge from the hospital. The cumulative incidence of SSIs varied from 0.7 percent after knee prosthesis to 9.2 percent after colon surgery.
ANTIMICROBIAL USE AND RESISTANCE IN EUROPEThe prevalence of antimicrobial use was estimated at 32.7 percent, with 466,226 patients receiving at least one antimicrobial on any given day in European acute care
hospitals in 2011-2012.For selected microorganisms reported in health care-associated infections in 2011-2012, the number tested was reported as follows, with (in parentheses) the percentage that were non-susceptible. Gram-positive cocci: methicillin-resistant Staphylococcus aureus, 1,071 (41.2 percent); vancomycin-resistant Enterococcus spp., 755 (10.2 percent); vancomycin-resistant E. faecalis, 455 (5.5 percent); vancomycin-resistant E. faecium, 205 (19.0 percent). Enterobacteriaceae (third-generation cephalosporin non-susceptible), 2,851 (33.4 percent): Escherichia coli, 1,292 (23.5 percent); Klebsiella spp., 726 (53.0 percent); K. pneumoniae, 594 (56.7 percent); K. oxytoca, 87 (24.4 percent); Enterobacter spp., 343 (40.5 percent). Enterobacteriaceae (carbapenem non-susceptible), 2,787 (7.6 percent): E. coli, 1,267 (3.6 percent); Klebsiella spp., 719 (19.3 percent); K. pneumoniae, 589 (22.6 percent); K. oxytoca, 84 (0 percent); Enterobacter spp., 340 (3.5 percent). Other Gram-negative bacteria (carbapenem non-susceptible): Pseudomonas aeruginosa, 756 (31.8 percent); Acinetobacter baumannii, 292 (81.2 percent).
CONCLUSIONFor more information on infection with drug-resistant microorganisms, antibiotic resistance, drug resistance (treatment resistance), multidrug resistance, see the IPD database, with IPD map reports reflecting the countries/regions with the most published incidence and prevalence data available in the database. //
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