1. May 2012
CORTHOUGHTS
…a slow-burning
collection of
stem cell
disorders that
have clinicians
handcuffed when
it comes to
offering
meaningful
interventions.
Myelofibrosis and JAK Inhibition
Has development been a swing and a miss?
By David Querry
As a former brand manager working in the JakafiTM—a base hit, but no home run!
myeloproliferative disorder/neoplasm (MPN) In November of 2011, ruxolitinib became the
market, I have been keenly interested in the first-in-class selective JAK1 and JAK2 inhibitor
development and potential of JAK inhibition. to be FDA approved for use in patients with
This tumor type is often considered an high- and intermediate-risk myelofibrosis. The
“oncologic orphan” – a rare group of diseases approval was based on two phase 3 studies;
that challenge every hematologist but is COMFORT-I and COMFORT-II. While the
oftentimes viewed more as a condition rather studies served the purpose of satisfying
than a malignancy. They are a slow-burning regulatory requirements for FDA approval, they
collection of stem cell disorders that have unfortunately interjected as many questions as
clinicians handcuffed when it comes to offering answers around the pathogenic contribution of
meaningful interventions – limiting their the JAK-STAT pathway and the V617F
treatment approaches to phlebotomy, mutation. In short, these studies confirmed the
hydroxyurea, and other supportive care options. role of ruxolitinib in terms of partial response in
splenomegaly and alleviation of constitutional
Finding the “drugable” target? symptoms (interestingly regardless of the V617F
In early 2004 there was a great deal of mutation), but failed to demonstrate any
excitement with William Vainchenker’s discovery histopathologic, cytogenetic, or molecular
of the Janus kinase or JAK 2 (JAK2 V617F). Dr remissions. In addition, ruxolitinib was more
Vainchenker subsequently associated the likely to cause anemia and thromobocytopenia
JAK-2 mutation with BCR-ABL1-negative instead of improving it. Finally, because of a
myeloproliferative neoplasms. However, what failure to risk-stratify at randomization, a true
has been found is that the JAK-2 oncogene survival benefit cannot be supported in either
mutations are not MPN-specific nor can they be study. In fact, the lack of survival benefit was
traced back to ancestral clone. Instead these also suggested by another phase1/phase 2
mutations are “phenotype-modifying subclones long-term study of the drug performed at the
that do not necessarily contribute to leukemic Mayo Clinic. As a result, it is fair to say
transformation.” ruxolitinib is not the home run we were hoping
for, but it improves disease-related
symptomatology, and is therefore a solid single.
INTERESTED IN LEARNING MORE? PLEASE CONTACT DAVID QUERRY @ DQUERRY@NAVICORGROUP.COM

2. Myelofibrosis and JAK Inhibition
CORTHOUGHTS May 2012
Has development been a swing and a miss?
By David Querry
Marketing implications for future reported no overall survival benefit for ruxolitinib
JAK inhibitors as compared to standard therapy across
Like it or not, the approval and data supporting different DIPSS criteria. In addition, while the
ruxolitinib will form the basis of expectations for data support the reduction in spleen volume,
future second and third generation JAK they fails to elaborate on the ruxolitinib
inhibitors in development. Future molecules withdrawal syndrome” – a communication
leveraging this pathway and seeking to improve challenge with which Incyte is most assuredly
patient outcomes in MPNs will need to wrestling.
consider the following:
3. Differentiation from initial experience
1. Help the market better understand the
The clinical data supporting ruxolitinib reinforce
disease pathology, diagnosis, and treatment
the current perception around the disease – it
options for this group of diseases
is all about reduction in spleen size, symptom
Break the “oncologic orphan” syndrome.
control, and QoL. While 93% of clinicians in a
MPNs are often still considered a nebulous
recent survey correlate spleen size to disease
mixed bag of symptoms. To ensure maximum
progression (reference: Life Science Advisors
penetration, pre-marketing programs directed
Jakafu Usage Survey, Jan 2012), future entries
at aiding in the recognition, diagnosis, and
into this market are going to need to design
sense of urgency to intervene in this
trials to demonstrate a more “active” therapy
malignancy will result in the recognition of a
against the disease rather than another
larger patient pool and more rapid uptake at
supportive care option – particularly if the
launch. The myelodysplastic syndrome (MDS)
molecule will demand a premium price.
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 Are you developing a “targeted” small
that elevating the severity of the condition, molecule, an immunomodulatory agent,
aligning it as a malignancy, and demonstrating a cytokine inhibitor, or something
different?
the therapy as the first "active" treatment for
MDS was critical to its early and continued Thinking through this part of the story
success. We believe Incyte left this door wide and aligning not only the unmet medical
open, and the company that steps into this need but also the association of the
opportunity will end up defining and owning molecule MOA to the pathway and
the market. disease pathology is going to be critical
to future success in the MPN
marketplace.
2. Manage customer expectations and
the story The Navicor Group, part of inVentiv
The most basic tenet of advertising and Health, is a full-service oncology/
launching brands! There are a small group of hematology-focused communications
KOLs who influence this market – you need to company. We partner with clients in
work with all of them, especially the Mayo phase II through full commercialization
Clinic. Trial designs that fail to look at risk to transform products into brands and
stratification and compare against placebo are patients into survivors. Give us a call or
send us an e-mail with your challenges.
not real-world and will limit the commercial
We are ready to tackle them!
story and value proposition. For example, data
reported in October 2011 in N Engl J Med
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.
INTERESTED IN LEARNING MORE? PLEASE CONTACT DAVID QUERRY @ DQUERRY@NAVICORGROUP.COM