Gilead’s rival to Incyte’s Jakafi stumbles in PhIII

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Subpar Phase III data added to Gilead's R&D woes

Gilead has posted subpar data from two Phase III trials of JAK inhibitor momelotinib in patients with the bone marrow disorder myelofibrosis, continuing its struggles in the clinic. The data raise doubts about momelotinib’s ability to hold its own against Incyte’s Jakafi, let alone unseat the blockbuster incumbent.

One of the Phase III trials pitted momelotinib against Jakafi in previously-untreated myelofibrosis patients. That study met its primary endpoint of noninferiority to Jakafi in terms of splenic response rates, defined as a reduction in spleen volume of 35% or more. Such declines were achieved by 26.5% of subjects in the momelotinib arm, compared to 29% in the Jakafi cohort.

Momelotinib fared worse against a key secondary endpoint that looked at symptom scores for the myeloproliferative neoplasms that affect myelofibrosis patients.

Failure to match Jakafi in symptom scores prompted Gilead to scrap plans to formally analyze three anemia-related secondary endpoints, despite a glance at the data suggesting momelotinib bested its rival against these measures. When Gilead acquired momelotinib in its $510 million takeover of YM Biosciences, the potential for the JAK inhibitor to control anemia was seen as giving it an edge over Jakafi, the effect of which is limited to reductions in spleen size.

The second trial gave momelotinib or best alternative treatment (BAT) to myelofibrosis patients who had previously received Jakafi. Gilead was hoping to show momelotinib triggered greater splenic response rates than BAT, but the JAK inhibitor failed to deliver. Momelotinib appears to compare favorably to BAT in terms of symptom scores and the anemia-related endpoints, but having missed the primary goal Gilead again opted against performing formal sequential statistical testing.

Gilead plans to discuss the data with regulators before deciding how to proceed. But, even if the noninferiority result is enough to get momelotinib approved, the top-line data are bereft of reasons to think the JAK inhibitor can steal market share from Jakafi.

If momelotinib is ultimately chalked up as a failure, it will join a fast-growing list of clinical setbacks for Gilead. In 2016, Gilead has delivered weak data from trials of cardiovascular candidate eleclazine, ulcerative colitis hopeful GS-5745 and repeat-failure simtuzumab.

The string of failures has ratcheted up pressure on Gilead to wheel and deal its way to a stronger pipeline. Or, as Barclays Analyst Geoff Meacham understatedly put it: “Given that the internal pipeline is struggling to produce candidates that could provide a significant offset to the projected decline in HCV sales, we think external deployment of capital in a deal will be favorably received by investors.”