In fresh blow to floundering PI3K space, FDA feedback drives MEI, Kyowa to halt blood cancer program

The dominoes keep falling in the PI3K space. After meeting with the FDA, Kyowa Kirin and MEI Pharma have stopped development of their B-cell malignancy prospect zandelisib outside of Japan.

Emerging evidence that PI3K inhibitors may shorten life expectancy has driven the FDA to harden its stance on the class of blood cancer drugs. At the start of the year, Gilead Sciences pulled an accelerated approval for Zydelig after finding enrollment in a confirmatory study “an ongoing challenge” and Incyte withdrew a submission for its rival PI3K inhibitor parsaclisib because it would be impossible to complete confirmatory trials “within a time period that would support the investment.”

Armed with data linking zandelisib to a 70% response rate in an open-label, single-arm phase 2 trial, MEI planned to file for accelerated approval despite the broader upheaval. The FDA shut down that prospect earlier this year by requesting data from a randomized study, and has now seemingly killed off any hopes of zandelisib coming to market in the U.S.

In a statement to disclose the change in strategy, MEI CEO Daniel Gold, Ph.D., said the partners jointly took the step “based on the most recent guidance received from the FDA at a late November meeting.” Gold still thinks zandelisib can meet the need for new options to treat relapsed or refractory indolent non-Hodgkin lymphomas, but the sums no longer make sense. 

“In light of FDA’s guidance, we no longer believe clinical development can be completed within a time period that would support further investment, or with sufficient certainty of the regulatory requirements to justify continued global development efforts,” the MEI CEO said. 

The partners, reportedly with the support of the FDA, initially continued their phase 3 COASTAL clinical trial after finding out that they would need randomized data to come to market in the U.S. However, the FDA provided additional guidance on the design and statistical analysis of COASTAL late last month that led the partners to conclude the required changes tipped the scales against continuing the study.

While COASTAL and the phase 2 CORAL trial will immediately wind down, Kyowa Kirin is continuing work including the phase 2 MIRAGE study evaluating Japanese patients with B-cell non-Hodgkin lymphomas and will look into seeking approval in its home market based on midphase data. The big opportunity is gone, though, and Kyowa Kirin consequently took a 14.33 billion yen ($105 million) impairment loss.

Shares in MEI fell 36% to 25 cents in premarket trading. The company announced a "strategic realignment" in wake of the discontinuation of zandelisib. MEI will now focus on two earlier-stage assets, voruciclib and ME-344 for hematological malignancies and solid tumors, respectively. 

As a result, the company will execute layoffs, initially starting with 30% of the workforce that had been associated with development of zandelisib outside of Japan. Once these initial layoffs are conducted, MEI said there could be further cuts "to fully align resources going forward." With those measures initiated, MEI believes it has enough cash to fund development through clinical data for voruciclib and ME-344. 

“In light of the determination we made with our global partner, Kyowa Kirin, to discontinue development of zandelisib outside of Japan after a recent meeting with FDA, we have had to make some tough decisions," said Gold.

MEI has also engaged a financial advisor "to help explore additional strategic opportunities."