“Courage does not always roar. Sometimes courage is the quiet voice at the end of the day saying, ‘I will try again tomorrow.’ “ ― Mary Anne Radmacher

Monique Canonico DO

Assistant Clinical Professor

University of Hawaii

John A. Burns School of Medicine

RESEARCH UPDATE 2013

OVERVIEW• Update on demographics

• Recent 3 orals approved

• Research updates

• Patient support websites

FACTS ON MS• Now 3:1 female to male

• Those with May birthdays may be more susceptible

• 400,000 people in US have in

• 2 million worldwide

FDA-Approved Disease-Modifying AgentsAubagio (teriflunomide)Avonex (interferon beta-1a)Betaseron (interferon beta-1b)Copaxone (glatiramer acetate)Extavia (interferon beta-1b)Gilenya (fingolimod)  Novantrone (mitoxantrone)Rebif (interferon beta-1a)Tecfidera (dimethyl fumarate)Tysabri (natalizumab)

GILENYA• Approved 2011

• Fingolimod is 0.5 mg orally once a day

• Most common side effects headache, flu, diarrhea

• Can cause swelling in eye, low heart rate, increased infections

AUBAGIO• Teriflunimide

• Once daily oral. Category X

• For relapsing remitting

• Blocks the production of overactive T and B cells

• Do not get certain vaccinations on this drug

• Numbness tingling, kidney problems, hair loss

TECFIDERA APPROVED MAR 27• Twice a day

• inhibit immune cells and molecules, and may have anti-oxidant properties that could be protective against damage to the brain and spinal cord

• Titrate up over 1-2 wks.

• Flushing and GI symptoms

WHEN SHOULD A PATIENT SWITCH THERAPIES?

• Neutralizing antibodies

• Adverse reactions

• Progression of disease

• Number of relapses and how well the patient recovers

INTERPRETING THE DRUG DATA• New drugs have been approved recently

• Tecfidera was compared to Copaxone

• Gilenya and laquinimod compared to Avonex

• Aubagio compared to Rebif

• Some clinical and MRI outcomes significantly favored Gilenya over Avonex whereas laquinimod did not show superiority

INTERPRETING THE DRUG DATA(CONT.)• Tecfidera showed a reduction in MRI

activity as compared to Copaxone

• NONE OF THESE DRUGS HOWEVER SHOWED A BENEFIT VS THEIR COMPARATOR ON DISABILITY PROGRESSION

• In most instances the comparator did not reflect the primary outcome of the trial

INTERPRETING THE DRUG DATA(CONT.)

• Best way to compare efficacy is by well designed head to head comparison trials

• These require large numbers of patient and are expensive

• Whether these will occur remains to be seen

• Preliminary evidence from the oral drug trials suggests comparative efficacy; more studies are needed

INTERPRETING THE DRUG DATA(CONT.)• It is still early in the assessment of

safety

• The injectables have been shown to have excellent safety records over long periods of time

Moving on to the latest research….

NEW MS DIAGNOSTIC TOOLS ON HORIZON• Published in Practical Neurology Dec

2012

• “MSPrecise”

• Spinal fluid analysis

• Next generation sequencing assay that evaluates the key genes involved in the immune system of people being evaluated for ms

RETINA’S THICKNESS LINKED TO MS SEVERITY• Dec 12 Practical Neurology

• Measuring the thickness of the retina by OCT (Optical Coherence Tomography

• The retina reflects what is happening in the brain

• May help determine treatment response

PAROXYSMAL DYSARTHRIA AND ATAXIA• Jan 15, 2013 issue of Neurology p. 311

• Initially described by Henry Parker, Irish neurologist, 1946

• Combination associated with MS

• Sudden brief onset of symptoms; could happen many x an hour

• Double vision, tingling, face pain, itching, ataxia

NEW DRUG IN DEVELOPMENT• Published online edition of Neurology

Nov 28,12

• Suvorexant: for insomnia!

• Works on a different brain receptor

• It blocks wakefulness-regulating chemical messengers in the brain called orexins

• Merck is testing it

VACCINES FOR MS TREATMENT• Published in Science of MS Management Apr

2012

• One of the vaccines being tested has genetically engineered DNA that encodes myelin basic protein(a major cytokine target for MS)

• Another strategy for vaccines is t cell vaccination

• Tovaxin is a T cell vaccine based on the individual’s profile based on their t cell response

Your Society at Work !

Apr 17, 2013The National Multiple Sclerosis Society has committed another $18 million to support up to 65 new MS research projects.These new awards are part of a comprehensive Research strategy aimed at stopping MS, restoring function that has been lost, and ending the disease forever.

NMSS FUNDING STUDY ON AXONA• a clinical trial to determine potential

benefits  of Accera’s medical food, Axona® (caprylic triglyceride),  on cognitive impairment in people with MS

• Axona is an FDA-regulated “medical food”

NMSS FASTFORWARD PROGRAMFUNDS DEVELOPMENT OF DRUG• Spasticity is a common and often painfu

l symptom of MS that involves feelings of stiffness, tightness

• Potential therapy being developed VSN16R

• To help with spasms in all forms of MS including chronic progressive

UK MS SOCIETY FUNDS RESEARCH ON DRUG • This is a study on a drug called

amiloride

• It is a blood pressure medicine

• 14 people enrolled

• Atrophy was reduced

• Larger trial planned

Perseverance is a great element of success. If you only knock long enough and loud enough at the gate, you are sure to wake up somebody.

Henry Wadsworth Longfellow

Large trial in progressive MS: A poster presentation by Dr. David Miller of University College London and an international team suggested that good progress is being made in a large trial of Gilenya® being supported by Novartis. The study involves more than 1000 participants with primary-progressive MS, and it’s designed to determine if Gilenya can slow down MS disability compared to inactive placebo after 3 to 5 years of treatment (Abstract P07.116)

New form of existing therapy for relapsing MS: Dr. Peter Calabresi of Johns Hopkins University presented results of an international, phase 3 trial of peginterferon beta-1a in relapsing MS, a new form of Avonex® designed to stay in the body longer than the standard form. The results over one year suggest peginterferon injected under the skin every two or four weeks was effective in reducing relapse rates and also reduced the risk of progression of disability. This study is continuing into a second year. Trial sponsor Biogen Idec has announced plans to apply for regulatory approval in 2013.

March 2013Copaxone® in fewer doses: Dr. Omar Khan of Wayne State University, Michigan, presented results of a one-year phase 3 trial supported by Teva Pharmaceuticals suggesting that under-the-skin injections of twice the standard dose of Copaxone, taken three times per week, were effective in reducing relapses and MRI-detected disease activity, and revealed no unexpected safety issues.

EXCESS MORTALITY IN MS LARGELY FROM SMOKING• LYON, France Oct 12 -- Much of the early

mortality seen in multiple sclerosis patients is related to their smoking habits, a researcher said here.

• In a prospectively followed cohort of nearly 900 MS patients, 68% of those who died in a 40-year period were current or former smokers, compared with 50% of surviving patients, according to Ali Manouchehrinia of the University of Nottingham in England.

April 2013

Switching therapies: A large study in France called ENIGM tracked the impact of switching from therapy with Tysabri® to Gilenya.® Among 200 people who switched after an average of 30 months on Tysabri, there was a “washout” interval of 3 to 6 months in which no therapy was given and32% experienced a relapse. The researchers concluded that switching increases the likelihood of disease reactivation, and that the washout period should not be longer than 3 months.

EMERGING THERAPIES 2013• Octelizumab-futher testing; treats

relapsing AND progressive

• Laquinamod-elevated liver tests but did decrease progression

• Alemtuzumab-IV drug; FDA evaluating

• Dacluzumab-SQ monthly; decreased MRI and disease progression in preliminary studies

Sugar and progression: a small study from Drs. Wael Richeh, Jesus Lovera and colleagues at Louisiana State University gives food for thought. They asked whether blood sugar is linked to levels of MS disability, and found that people with higher levels of glucose were more likely to have higher levels of disability. This important lead needs more study to prove a role for blood sugar in MS progression. 

April 2013Exercise and the brain: A small study from Society-supported scientists Drs. Victoria Leavitt, and others at the Kessler Foundation tested whether aerobic exercise impacts the brain. Using MRI scans and memory tests, they found hints that aerobic exercises (30 minute sessions, 3 times a week, over 3 months) improved memory and increased the volume of the hippocampus, a part of the brain involved with memory and other functions. These preliminary results require additional follow-up.

April 2013Exercise and fatigue: German researchers reported on the impacts of longer-term aerobic exercise to build endurance in people with MS. This study involved 60 people split into two groups: those with fatigue and those without fatigue. Both groups did individualized endurance exercise on treadmills for 12 months. After 6 months of exercise, both groups had improved oxygen consumption, but those who started out with fatigue didn’t show improvement in their fatigue scores until 9 months into the program

CCSVI treatment in MS: First results from a controlled endovascular treatment trial (percutaneous transluminal venous angioplasty) were presented by Drs from State University of New York at Buffalo. In this blinded study, 9 people had the angioplasty and 10 had a sham treatment. At six months, the team did not detect adverse events from the treatment, but also found that it failed to provide sustained improvement in venous outflow. They also found that those whose veins increased In outflow tended to have increased MS disease activity seen on MRI. (Emerging Science Poster P04.273)

APRIL 2013• Lower body weight may increase risk of

PML in those who take Tysabri

• Less than 60 kg

Sep 24, 2012Results of a placebo-controlled, 12-week clinical trial were recently published, showed that Ginkgo biloba failed to improve cognitive function in people with MS. The study involved 121 people with all types of MS whose cognitive tests showed some cognitive impairment. After 12 weeks, no differences were seen between those on Ginkgo and those taking placebo in any of the outcome measures.

Gingko does not improve cognition

Three studies published March 2013 by collaborators at Yale, Harvard and MIT/Broad Institute suggest that dietary salt can speed the development of an MS-like disease in mice, and provide new insights on immune system activity involved in MS.

RESOURCES• nationalmssociety.org

• Mscando.org (lifestyle empowerment)

• Msworld.org (message boards and chat)

• Nfcares.org (supports those who care for their loved ones)

RESOURCES• Assistive Technology Resource Centers

of Hawaii414 Kuwili Street, Suite 104Honolulu, HI 96817(808) 532-7110 (Local)

RESOURCES: ASSISTIVE TECHNOLOGY• Offers a wide variety of assistive

technology (AT) equipment loaned free of charge through centers across the state. Offers customized workshops in AT to meet the specific training needs of university students, professionals, persons with disabilities and their families in Hawaii.

“If you are going through hell, keep going.” ― Winston Churchill