One of these Gilead studies compares momelotinib head-to-head against Jakafi, another Jak inhibitor and the current standard of care in myelofibrosis marketed by Incyte (INCY - Get Report) and Novartis (NVS - Get Report) . The second study compares Gilead's momelotinib against best alternative care in patients previously treated with Jakafi.
Results from both of Gilead's momelotinib studies are expected this quarter.
Gilead has struggled mightily to produce a successful drug from its research pipeline that isn't targeted at HIV or hepatitis C, so the outcome of the momelotinib studies are acutely important. Sales of Zydelig, Gilead's only approved blood cancer drug, have been disappointing to date and safety issues forced the company to abandon front-line combination studies earlier this year.
For Incyte, momelotinib represents the last near-term threat to its dominance of the myelofibrosis treatment market. Five years after approval, Jakafi is a blockbuster drug with 2016 sales expected to reach $852 million in the U.S. and $577 million outside the U.S., according to FactSet. [Incyte records U.S. Jakafi sales; Novartis reports ex-U.S. sales and pays a royalty to Incyte.]
By 2018, Jakafi worldwide sales are projected to exceed $2.1 billion, according to FactSet. (Jakafi sales forecasts include use in patients with polycythemia vera, a similar bone marrow disease for which it's also approved.)
Jakafi is an effective myelofibrosis drug but a lack of competition has helped. Drugs that could have potentially competed against Jakafi from Sanofi (SNY - Get Report) , Celgene (CELG - Get Report) , AstraZeneca (AZN - Get Report) , CTI Biopharma (CTIC - Get Report) and Geron (GERN - Get Report) have either been discontinued due to failed studies or hit significant developmental roadblocks.
For the near term, Gilead and momelotinib remains the last viable Incyte competitor.
Myelofibrosis is a disorder in which abnormal bone marrow stem cells produce scar tissue that replaces healthy marrow. Patients with myelofibrosis suffer from enlarged spleens and anemia.
Gilead came to own momelotinib through the acquisition of YM Biosciences for $510 million in 2012. Known as CYT387 at that time, momelotinib was controversial. Small phase II studies suggested momelotinib might be superior to Jakafi by both shrinking enlarged spleens and controlling anemia. (Jakafi doesn't do the latter.) In 2010 and 2011, the momelotinib data were a raging bull-bear debate amongst biotech investors, with many doubting the phase II study results would hold up in larger phase III studies.
Of the two phase III studies of momelotinib nearing completion, the head-to-head study against Jakafi offers the most potential impact. The study enrolled 400 patients with previously untreated myelofibrosis and randomized them to treatment with momelotinib or Jakafi for 24 weeks. The primary endpoint is the percentage of patients with a spleen response, defined as 35% or more reduction in spleen volume.
To win, Gilead must show statistical non-inferiority between momelotinib and Jakafi on the spleen response endpoint. That might get momelotinib approved, but to persuade doctors to use the drug, Gilead needs to demonstrate a numerically superior spleen response over Jakafi. That's what investors eyeing the results will look for.
Jakafi demonstrated a 42% spleen response rate in a placebo-controlled phase III study, one of two which supported the drug's approval. With longer follow up, the drug also demonstrated a survival benefit versus placebo.
For secondary endpoints, Gilead is also comparing momelotinib and Jakafi on their ability to improve symptoms of myelofibrosis and alleviate anemia via transfusion independence.
On safety, Jakafi is associated with relatively high rates of anemia and thrombocytopenia, or low platelet counts. Momelotinib's most significant safety overhang is peripheral neuropathy, or nerve pain.