MEI suffers from the FDA’s brake on accelerated approvals

The FDA is holding an adcom next month to look at whether randomised data should be required to support approval of PI3K inhibitors – but in at least one case it has already made its decision. The surprise denial of accelerated approval to MEI’s zandelisib, based on a single-arm phase 2 trial, Tidal, in follicular or marginal zone lymphoma, has wiped out 58% of the company’s market cap. MEI must now complete the more rigorous phase 3 Coastal study to get the drug on the market, but its current cash reserves can only to stretch to completion of enrolment into Coastal, in 2024. MEI said the agency’s position on assessing PI3K inhibitors solely based on single-arm studies “appears to have evolved”, as well it might considering the series of discontinuations, withdrawals and clinical holds to which this class has been subject in recent months. Still, the FDA’s volte-face is arguably unfair to MEI: Stifel analysts point out that every PI3K-delta inhibitor greenlit so far was granted accelerated approval on efficacy and safety data notably poorer than zandelisib’s. 

Selected PI3K inhibitors in haematological cancers
Company Project Pharmacology Indication Status
Gilead Sciences  Zydelig PI3K delta  FL & SLL Accelerated approval granted Jul 2014; withdrawn Jan 2022
Bayer  Aliqopa Pan-PI3K 3rd-line FL Accelerated approval granted Sep 2017; filed for full approval Jun 2021
TG Therapeutics Ukoniq PI3K delta  2nd-line MZL;
4th-line FL 
Accelerated approval granted Feb 2021; U2 combo (that includes Ukoniq) placed on partial clinical hold, Jan 2022, both products will be discussed at FDA ad com in April
Incyte  Parsaclisib PI3K delta  3rd-line+ FL and others Discontinued in ph3, Jan 2022
MEI Pharma/
Kyowa Kirin
PI3K delta  3rd-line+ FL FDA says ph3 data, and full approval, are now required
FL=follicular lymphoma; MZL=marginal zone lymphoma; SLL=small lymphocytic leukaemia. Source: Evaluate Pharma & company communications.

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