Bayer to Voluntarily Withdraw PI3Kα/δ Inhibitor Copanlisib (Aliqopa) from U.S. Market Following Failed Confirmatory Trial

Recently, according to foreign media FirstWord reports, Bayer has decided to withdraw the PI3Kα/δ inhibitor copanlisib (trade name: Aliqopa) from the U.S. market because the post-marketing study (CHRONOS-4) failed to confirm the clinical benefit of copanlisib.

In September 2017, copanlisib received accelerated FDA approval for marketing based on the positive results of the Phase II CHRONOS-1 study, for the treatment of patients with relapsed follicular lymphoma (FL) who have received at least two prior lines of therapy.

The CHRONOS-1 study is a multicenter, open-label, single-arm clinical trial that evaluated the efficacy and safety of 0.8 mg/kg or 60 mg copanlisib in patients with relapsed FL.

The results showed that, among 104 evaluable FL patients, the objective response rate (ORR) was 58.7%, with a complete response (CR) rate of 14.4% and a partial response (PR) rate of 44.2%; the median duration of response (DOR) was 12.2 months.

Among 168 patients assessable for safety (including those with FL and other hematologic malignancies), the most common adverse reactions (incidence ≥20%) included hyperglycemia, diarrhea, fatigue, hypertension, decreased white blood cell count, decreased neutrophil count, nausea, lower respiratory tract infection, and decreased platelet count. The most common grade 3-4 adverse reactions included hyperglycemia, leukopenia, hypertension, decreased neutrophil count, and lower respiratory tract infection. Severe non-infectious pneumonia occurred in 6% of patients.

Following the accelerated approval of copanlisib, Bayer conducted the CHRONOS-4 study (n=551) to further validate the drug's efficacy and safety. Unfortunately, the study failed to meet its primary endpoint of significantly extending progression-free survival (PFS), and detailed results have not yet been released.

This is already the fourth withdrawal announcement in the PI3K inhibitor field, with the previous three being idelalisib (PI3Kδ inhibitor, Gilead), umbralisib (PI3Kδ/CK1ɛ inhibitor, TG Therapeutics), and duvelisib (PI3Kδ/γ inhibitor, Secura Bio).

Idelalisib was withdrawn from the market due to safety issues (see: ), the withdrawal reason for duvelisib is similar to that of Idelalisib (see: ), and umbralisib was withdrawn because of unclear clinical benefits (see: ).

Besides, Incyte withdrew its marketing application for PI3Kδ inhibitor parsaclisib in the treatment of FL, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) in January 2022. However, the reason was unrelated to efficacy and safety.

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