Date post: | 21-Jun-2015 |
Category: |
Documents |
Upload: | the-navicor-group |
View: | 180 times |
Download: | 6 times |
INTERESTED IN LEARNING MORE? PLEASE CONTACT DAVID QUERRY @ [email protected]
Myelofibrosis and JAK InhibitionHas development been a swing and a miss?By David Querry
As a former brand manager working in the
myeloproliferative disorder/neoplasm (MPN)
market, I have been keenly interested in the development and potential of JAK inhibition.
This tumor type is often considered an
“oncologic orphan” – a rare group of diseases
that challenge every hematologist but is
oftentimes viewed more as a condition rather than a malignancy. They are a slow-burning
collection of stem cell disorders that have
clinicians handcuffed when it comes to offering
meaningful interventions – limiting their
treatment approaches to phlebotomy, hydroxyurea, and other supportive care options.
Finding the “drugable” target?
In early 2004 there was a great deal of
excitement with William Vainchenker’s discovery of the Janus kinase or JAK 2 (JAK2 V617F). Dr
Vainchenker subsequently associated the
JAK-2 mutation with BCR-ABL1-negative
myeloproliferative neoplasms. However, what
has been found is that the JAK-2 oncogene mutations are not MPN-specific nor can they be
traced back to ancestral clone. Instead these
mutations are “phenotype-modifying subclones
that do not necessarily contribute to leukemic
transformation.”
JakafiTM—a base hit, but no home run!
In November of 2011, ruxolitinib became the
first-in-class selective JAK1 and JAK2 inhibitor to be FDA approved for use in patients with
high- and intermediate-risk myelofibrosis. The
approval was based on two phase 3 studies;
COMFORT-I and COMFORT-II. While the
studies served the purpose of satisfying regulatory requirements for FDA approval, they
unfortunately interjected as many questions as
answers around the pathogenic contribution of
the JAK-STAT pathway and the V617F
mutation. In short, these studies confirmed the role of ruxolitinib in terms of partial response in
splenomegaly and alleviation of constitutional
symptoms (interestingly regardless of the V617F
mutation), but failed to demonstrate any
histopathologic, cytogenetic, or molecular remissions. In addition, ruxolitinib was more
likely to cause anemia and thromobocytopenia
instead of improving it. Finally, because of a
failure to risk-stratify at randomization, a true
survival benefit cannot be supported in either study. In fact, the lack of survival benefit was
also suggested by another phase1/phase 2
long-term study of the drug performed at the
Mayo Clinic. As a result, it is fair to say
ruxolitinib is not the home run we were hoping for, but it improves disease-related
symptomatology, and is therefore a solid single.
CORTHOUGHTS
…a slow-burning collection of
stem cell disorders that have clinicians
handcuffed when it comes to
offering meaningful
interventions.
Ma
y 2
01
2
INTERESTED IN LEARNING MORE? PLEASE CONTACT DAVID QUERRY @ [email protected]
Marketing implications for future
JAK inhibitors
Like it or not, the approval and data supporting ruxolitinib will form the basis of expectations for future second and third generation JAK inhibitors in development. Future molecules leveraging this pathway and seeking to improve patient outcomes in MPNs will need to consider the following:
1. Help the market better understand the
disease pathology, diagnosis, and treatment options for this group of diseases
Break the “oncologic orphan” syndrome.
MPNs are often still considered a nebulous
mixed bag of symptoms. To ensure maximum
penetration, pre-marketing programs directed at aiding in the recognition, diagnosis, and
sense of urgency to intervene in this
malignancy will result in the recognition of a
larger patient pool and more rapid uptake at
launch. The myelodysplastic syndrome (MDS) market is a perfect analog demonstrating the
importance of this step in the commercial-
ization process. As the agency of record
launching Vidaza®, The Navicor Group believed
that elevating the severity of the condition, aligning it as a malignancy, and demonstrating
the therapy as the first "active" treatment for
MDS was critical to its early and continued
success. We believe Incyte left this door wide
open, and the company that steps into this opportunity will end up defining and owning
the market.
2. Manage customer expectations and
the storyThe most basic tenet of advertising and
launching brands! There are a small group of
KOLs who influence this market – you need to
work with all of them, especially the Mayo
Clinic. Trial designs that fail to look at risk stratification and compare against placebo are
not real-world and will limit the commercial
story and value proposition. For example, data
reported in October 2011 in N Engl J Med
reported no overall survival benefit for ruxolitinib
as compared to standard therapy across
different DIPSS criteria. In addition, while the data support the reduction in spleen volume,
they fails to elaborate on the ruxolitinib
withdrawal syndrome” – a communication
challenge with which Incyte is most assuredly
wrestling.
3. Differentiation from initial experience
The clinical data supporting ruxolitinib reinforce
the current perception around the disease – it
is all about reduction in spleen size, symptom control, and QoL. While 93% of clinicians in a
recent survey correlate spleen size to disease
progression (reference: Life Science Advisors
Jakafu Usage Survey, Jan 2012), future entries
into this market are going to need to design trials to demonstrate a more “active” therapy
against the disease rather than another
supportive care option – particularly if the
molecule will demand a premium price.
Myelofibrosis and JAK InhibitionHas development been a swing and a miss?By David Querry
CO
RTH
OU
GH
TS
Ma
y 2
01
2
ABOUT THE AUTHOR With a mind for strategy and a heart for science, Dave
brings the perfect mix of marketing savvy and pharmaceutical
insight to The Navicor Group. Leveraging more than
22 years of experience, he provides strategic leadership
across a variety of clients.
Are you developing a “targeted” small
molecule, an immunomodulatory agent, a cytokine inhibitor, or something
different?
Thinking through this part of the story and aligning not only the unmet medical
need but also the association of the molecule MOA to the pathway and
disease pathology is going to be critical
to future success in the MPN marketplace.
The Navicor Group, part of inVentiv Health, is a full-service oncology/
hematology-focused communications
company. We partner with clients in phase II through full commercialization
to transform products into brands and patients into survivors. Give us a call or
send us an e-mail with your challenges.
We are ready to tackle them!