FDA Puts Blood Cancer Nods Under Scrutiny On Substantial Toxicity Profile Of PI3K Drugs

The FDA aims to put the PI3K inhibitor drug class under a more stringent regulatory scope as the inhibitor has demonstrated substantial toxicity.
In nearly all of the randomized clinical trials, patients randomized to the PI3K inhibitor arm experienced increased rates of fatal adverse events (AEs), serious adverse events (SAEs), Grade 3 or greater AEs, and treatment modifications or discontinuation due to AEs.
Related: Gilead Withdraws Use Of Zydelig In Two Forms Of Blood Cancer In US.
Six randomized trials evaluating a PI3K inhibitor have demonstrated a higher rate of death or concerning OS results suggesting potential harm to patients, the FDA said in a briefing document ahead of an advisory committee meeting scheduled for Thursday.
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The "unprecedented" observation raises a red flag for PI3K inhibitor approvals based on single-arm trials.
The drug reviewers cannot correctly evaluate overall survival, the FDA says. Therefore, the agency says future PI3K approval should use randomized clinical trials with active comparators.
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The FDA also mentioned that drug development programs focused on determining the maximum tolerated dose in its review document.
Hence, lower doses, which may offer significant efficacy with reduced toxicity, are generally not explored extensively.
The FDA has approved four PI3K inhibitors for various blood cancers: Gilead Sciences Inc's GILD Zydelig (idelalisib), Bayer AG's BAYRY Aliqopa (Copanlisib), Secura Bio's Copiktra (duvelisib) and TG Therapeutics Inc's TGTX, Ukoniq (umbralisib).
In 2020, Verastem Oncology VSTM divested Copiktra rights to Secura Bio for up to $381 million.
Novartis AG's NVS Piqray, a PI3K alpha-specific inhibitor approved for breast cancer, is not part of the group under FDA scrutiny.