- 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.
- Related: Incyte Pulls Parsaclisib US Application For Lymphoma Treatment.
- 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.
- Read Next: TG Therapeutics Retracts FDA Request For Ublituximab / Ukoniq Combo In Blood Cancers.
- 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 (NASDAQ:GILD) Zydelig (idelalisib), Bayer AG's (OTC:BAYRY) Aliqopa (Copanlisib), Secura Bio's Copiktra (duvelisib) and TG Therapeutics Inc's (NASDAQ: TGTX), Ukoniq (umbralisib).
- In 2020, Verastem Oncology (NASDAQ:VSTM) divested Copiktra rights to Secura Bio for up to $381 million.
- Novartis AG's (NYSE:NVS) Piqray, a PI3K alpha-specific inhibitor approved for breast cancer, is not part of the group under FDA scrutiny.
