After FDA setback, MEI, Kyowa confirm phase 2 efficacy with Japanese blood cancer data drop

Kyowa Kirin and MEI Pharma have posted more midphase data on their oncology candidate zandelisib, confirming the efficacy seen in an earlier trial of the PI3K delta inhibitor. But with the FDA raising the bar for the asset, the companies need an ongoing phase 3 to deliver to get the prospect to the U.S. market.

The latest data come from the phase 2 MIRAGE clinical trial, which enrolled 61 patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma in Japan to receive two cycles of zandelisib. At an interim data review, 75.4% of participants had responded to the therapy. The complete response rate was 24.6%, and it is too early to accurately estimate the duration of response.

Kyowa Kirin and MEI posted similar data from a global clinical trial of zandelisib, the phase 2 TIDAL study, one year ago. In the earlier trial, the partners linked the candidate to objective and complete response rates of 70.3% and 35.2%, respectively.

When MEI posted the TIDAL data, it planned to seek accelerated approval on the strength of the results. The FDA closed the door on that plan earlier this year by stating it needs data from randomized trials to assess the safety and efficacy of PI3K inhibitors, including zandelisib. That position has reshaped the market—and set back MEI’s hopes of bringing the drug to the U.S. market. 

The shifting sands of the PI3K inhibitor space reflect the FDA’s concerns about results that suggest the molecules may shorten life expectancy. Because other PI3K inhibitors came to market based on data from single-arm studies, it has been hard for the FDA to tease out the effect the drugs have on the key endpoint of overall survival. Requiring randomized clinical trials could clear up the uncertainty. 

As a relatively small, single-arm clinical trial, MIRAGE adds little to the debate about the drug class. The available safety and tolerability data show the rates of discontinuation because of treatment-emergent adverse events and grade 3 or worse elevated liver enzymes were higher in the study, respectively 14.8% and 8.2%, than in TIDAL, 9.9% and 1.7%, but the critical survival question remains unanswered.

Shares in MEI, which have taken a battering this year, fell 5% to 38 cents in premarket trading.