COMFORT-II data show INC424 provides marked clinical improvement in patients with myelofibrosis, measured by reduction in spleen size at 48 weeks compared to best available therapy
- Myelofibrosis is a debilitating disease with a poor prognosis and limited available therapies, presenting a critical unmet medical need
- Complete data to be submitted to an upcoming medical meeting
- Two Phase III trials provide basis for worldwide regulatory filings in Q2 2011
Basel, March 15, 2011 - Novartis announced today that a pivotal Phase III trial of the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) has met its primary endpoint of significantly reducing spleen size in patients with myelofibrosis (MF). INC424 is a potent, selective inhibitor of the JAK1 and JAK2 tyrosine kinases.

The European study, called COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy), showed treatment with INC424 provided a statistically significant reduction in spleen size in patients with primary MF, post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF), when compared with best available therapy, administered at doses and schedules determined by the investigator. The safety profile of INC424 was consistent with previous studies. Complete study data will be submitted to an upcoming medical meeting.

These results support findings from another large Phase III clinical trial (COMFORT-I) conducted by the collaboration partner, Incyte Corporation, in the US, Canada and Australia comparing treatment with INC424 to placebo in patients with MF at 24 weeks. In addition, a Phase I/II study published in the September 16, 2010 issue of The New England Journal of Medicine showed that treatment with INC424 resulted in marked, fast and durable clinical benefits in patients with MF. These benefits included alleviation of debilitating symptoms and reduction of spleen size, an accepted measurement of clinical improvement in MF[1],[2].

Results of the COMFORT-II and COMFORT-I clinical trials will form the basis of worldwide regulatory filings, planned to begin in the second quarter of 2011. The INC424 investigational studies constitute the largest clinical trial program in MF to date.

"We are pleased to reach this important milestone in our collaboration to develop INC424, a compound representing potential progress for patients with myelofibrosis, a serious malignant disease with limited treatment options," said Hervé Hoppenot, President, Novartis Oncology. "INC424 illustrates our mission to turn the promise of innovative, pathway-based compounds into the reality of therapies for patients with unmet medical needs."

Myelofibrosis is an uncommon, life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly), debilitating symptoms including fatigue, night sweats and pruritus, poor quality of life, weight loss and shortened survival. Myelofibrosis has a poor prognosis and limited treatment options[1],[3]. Although allogeneic stem cell transplantation may cure MF, the procedure is associated with significant morbidity and mortality and is usually appropriate only in younger patients[3]. The five-year survival rate after transplantation is approximately 50%[4].

Novartis licensed INC424 from Incyte for development and potential commercialization outside the US. Incyte has retained rights for the development and potential commercialization of INC424 in the US. Both the European Commission (EC) and the US Food and Drug Administration (FDA) have granted INC424 orphan drug status for MF.

Study details
COMFORT-II is a randomized, open-label Phase III study of INC424 versus best available therapy that enrolled 219 patients with primary MF, PPV-MF or PET-MF in 56 study locations in Europe. Two-thirds received INC424 and one-third received best available therapy, administered at doses and schedules determined by the investigator. The primary endpoint for COMFORT-II is the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline to week 48 as measured by MRI (or CT scan in applicable patients). Reduction of spleen size is an accepted measurement for clinical improvement in MF[1],[2]. COMFORT-II is sponsored by Novartis[5].

About myelofibrosis
Myelofibrosis is a Philadelphia chromosome-negative myeloproliferative neoplasm[1]. Of the JAK-associated myeloproliferative neoplasms, MF carries the greatest risk of a poor prognosis, including transformation to fatal acute myelogenous leukemia. For MF patients in general, clinical findings such as splenomegaly and constitutional symptoms may be associated with significantly reduced quality of life[3],[6-8].