When Medivation ($MDVN) bought out the rights to CureTech's pidilizumab back in late 2014 in a $335 million deal, the San Francisco-based biotech trumpeted its entry into checkpoint inhibition with a drug that aimed right at PD-1, unleashing a T cell attack on cancer.
Except that Medivation recently concluded that the drug doesn't work that way after all--and now the FDA has red-flagged a pivotal study of the drug, halting the trial through a partial clinical hold while Medivation takes another stab at explaining the mechanism of action (MOA).
"Under its investigational new drug application (IND) for MDV9300, Medivation has advised the U.S. Food and Drug Administration (FDA) of this conclusion (concerning PD-1), and the FDA has placed the IND on partial clinical hold and requested Medivation to revise relevant statements in the related investigator brochure, protocols and informed consent documents," the San Francisco-based biotech revealed in an SEC filing on Monday. "Medivation may not enroll patients into its Phase II clinical trial evaluating the safety and efficacy of MDV9300 in patients with relapsed or refractory diffuse large B-cell lymphoma until such statements are revised and the partial clinical hold is removed."
Medivation--which paid a modest $5 million upfront to get its hands on the drug--says it's scrambling now to define the actual MOA of the drug, which has been in the clinic for years. The biotech adds that it doesn't believe the FDA has any safety issues with the drug--which would threaten the whole program--and thinks it can respond to the agency's requests in the next few weeks.
The actual hold order from the FDA is not publicly available.
Back in December, Medivation was talking up the prospects of using its newly launched Phase II study of pidilizumab for U.S. and European applications for relapsed or refractory diffuse large B-cell lymphoma. By that time, the company had dropped the reference to PD-1, talking about the drug's ability to bolster T lymphocytes and rev up natural killer cells.
Pidilizumab has taken a long and somewhat tortured path to get to this crossroads, all of it centered on an MOA that didn't actually apply. Teva ($TEVA) had the drug, until then-CEO Jeremy Levin wrote it off along with $109 million, saying that they were too late to the checkpoint party to have a big impact. Then in late 2013 an investigator unveiled new data from a small study, claiming that the PD-1 approach in combination with Rituxan offered a promising approach to follicular lymphoma.
After a little more than 15 months of therapy, 19 of the 29 patients--or 66%--taking the combo had a complete or partial response, said Sattva Neelapu, the lead investigator at the University of Texas MD Anderson Cancer Center. Most of that group, 15 patients--or 52%--had a complete response, says Neelapu, an associate professor of lymphoma/myeloma. And the drug produced none of the grade 3 or 4 adverse events that raise safety concerns, triggering only "mild effects" among a group of patients with a median age of 60.
That seems good enough for most investors. Medivation's shares dropped 2% yesterday.
- here's the SEC filing