Regeneron/Sanofi Voluntarily Withdraws sBLA for PD-1 Inhibitor Libtayo in Cervical Cancer Indication

On January 28, Regeneron/Sanofi announced the voluntary withdrawal of the supplemental Biologics License Application (sBLA) for Libtayo (cemiplimab) as a second-line treatment for metastatic cervical cancer with disease progression or recurrence after chemotherapy. The withdrawal was due to the companies' inability to reach an agreement with the FDA on the confirmatory clinical study required post-approval. The application had received Priority Review designation from the FDA on September 28, 2021, with a PDUFA date of January 30, 2022.

Regeneron/Sanofi's withdrawal of the marketing application this time is another signal of the FDA tightening the review standards for PD-1 class drugs. The sBLA submitted by Regeneron/Sanofi was based on the results of an open-label, international multicenter, Phase III trial, EMPOWER-Cervical 1 (NCT03257267). This study evaluated the efficacy and safety differences of Cemiplimab versus investigator’s choice chemotherapy in 608 patients with recurrent or metastatic cervical cancer whose disease progressed after receiving platinum-based chemotherapy across 14 countries. The results showed that Cemiplimab significantly improved OS (12.0 vs 8.5 months).

On October 22, 2021, Agenus similarly announced the withdrawal of its marketing application for balstilimab monotherapy, a PD-1 antibody, for patients with recurrent or metastatic cervical cancer whose disease progressed after chemotherapy. The application was accepted by the FDA on June 17, 2021, and granted Priority Review, with a PDUFA date of December 16, 2021.

Agenus conducted the largest single-arm study to date in cervical cancer patients with recurrence or metastasis after chemotherapy. Among 140 evaluable patients, the ORR of balstilimab was 20% in PD-L1 positive patients and 8% in PD-L1 negative patients. In comparison, the ORR of Keytruda monotherapy in these two populations was 14.3% (with CR at 2.6%) and 0%, respectively. Based on these results, Agenus submitted a marketing application for balstilimab to the FDA.

So far, pembrolizumab remains the only PD-1/PD-L1 class drug approved for cervical cancer indications, covering both second-line and first-line treatments. Additionally, the closest to reaching the market are cadonilimab (PD-1/CTLA-4 bispecific antibody) from China's Akeso Biopharma and socazolimab (PD-L1) from Lee's Pharmaceutical, both of which have submitted marketing applications in China for recurrent or metastatic cervical cancer.