May 2012                                 CORTHOUGHTS           …a slow-burning                collection of               ...
Myelofibrosis and JAK InhibitionCORTHOUGHTS May 2012                          Has development been a swing and a miss?    ...
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Cor thoughts myelofibrosis_may2012

  1. 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. 2. Myelofibrosis and JAK InhibitionCORTHOUGHTS 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