Gilead Suffers Another R&D Setback as Myelofibrosis Drug Flops in Phase III, Gives Credence to Acquisition Urgency

November 17, 2016
By Mark Terry, BioSpace.com Breaking News Staff

Forest City, Calif. – Gilead Sciences announced top-line results from two Phase III clinical trials with mixed results. SIMPLY 1 and 2 evaluated momelotinib, a Janus kinase (JAK) inhibitor, in comparison to ruxolitinib or the best alternative therapy (BAT) in patients with myelofibrosis.

The SIMPLIFY-1 study hit its primary endpoint, which was non-inferiority to ruxolitinib for splenic response rate at Week 24. However, the key secondary endpoint for response rate in total symptom score, was not achieved—which is to say, “non-inferiority” wasn’t achieved. Or without the double-negative, momelotinib was inferior to ruxolitinib or BAT for total symptom score.

There were three other pre-specified anemia-related secondary endpoints, which were proportion of patients who are transfusion independent, transfusion dependent, and transfusion rate. Improvements in all of those were observed in patients receiving momelotinig compared to ruxolitinib. But because the total symptom score (TTS) was inferior, formal sequential statistical testing wasn’t conducted.

In the SIMPLIFY-1 trial, a laundry list of side effects was noted, including thrombocytopenia, diarrhea, headache, dizziness, anemia and nausea.

SIMPLIFY-2 also did not meet the primary endpoint, which is to say, it wasn’t better than ruxolitinib in SRR24. The company also said, “Differences in favor of momelotinib were observed for the pre-specified secondary endpoints of TSS and one of the three anemia-related endpoints (transfusion independence), however, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.”

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, executive vice president of Research and Development and Chief Scientific Officer of Gilead, in a statement. “We plan to discuss these results with regulatory authorities to determine the next steps.”

That’s a significantly more diplomatic way of putting it than Adam Feuerstein, writing for TheStreet today did, when he encouraged Gilead to acquire Incyte Corporation , or, well, anybody, in order to bolster its sagging hepatitis C franchise.

“Buy Incyte,” he wrote. “You’ll get Jakafi, the best myelofibrosis drug on the market (as you well know since it just beat the pants off of your own myelofibrosis candidate momelotinib) plus a promising IDO inhibitor to help you—finally—establish a toehold in cancer immunotherapy.”

And this recent failure is only reinforcing what many analysts are thinking about Gilead’s research-and-development efforts. Joshua Schimmer, an analyst with Piper Jaffray, wrote, “After the close, Gilead announced top-line results from both Phase III studies of momelotinib for patients with MF, which were disappointing as the product appears, not surprisingly to us, inferior to Incyte’s ruxolitinib. While some improvements were noted on anemia-related endpoints, it’s unclear what value this product has moving forward. We have consistently viewed this asset as flawed and not a meaningful competitive threat to Incyte’s Jakafi (we saw no reason to include momelotinib in our Gilead or Incyte models), and today’s announcement again reinforces our view that Gilead’s low-quality R&D engine will yield a series of setbacks which will likely force the company into a value-creating science-overhaul, pipelines rest and aggressive M&A transaction(s). Which is a good thing because from what we can tell, no investors give them credit for the non-HIV/HCV/filgotinib pipeline.”

And Schimmer and Feuerstein aren’t the only ones urging Gilead to go shopping, sooner than later. The Motley Fool’s Keith Speights also offered a list of companies Gilead should buy, including Incyte Corporation (INCY), Tesaro , Kite Pharma , Intercept Pharmaceuticals and others.

And with $32 billion in cash, cash equivalents and marketable securities, Gilead has buying options. Speights writes, “Why settle for just one company when you can have them all?”