Regeneron and Sanofi bag breakthrough status for PD-1 latecomer

With five PD-1/PD-L1 inhibitors already on the market, new entrants are looking increasingly like the "me-too" brigade, but Regeneron and Sanofi have found a niche for their cemiplimab candidate—and snagged FDA breakthrough status to boot.

The U.S. regulator has awarded the designation to PD-1-targeting cemiplimab—also known as REGN2810—as a treatment for adults with locally-advanced and metastatic cutaneous squamous cell carcinoma (CSCC), which Sanofi and Regeneron say is the second deadliest and most common form of skin cancer after melanoma.

The two partners are pushing hard to bring cemiplimab to market quickly, pitching at a regulatory filing in the U.S. in the first quarter of 2018.

There's no hiding the fact that cemiplimab is going to be a late entrant to the market if approved, with two blockbuster PD-1 inhibitors already on the market from Bristol-Myers Squibb and Merck & Co with an array of indications, and three PD-L1 drugs from Roche, AstraZeneca and Merck KGaA/Pfizer nipping at their heels.

That said, there is an emerging school of thought that distinguishes between PD-1 and PD-L1 drugs rather than lumping them together as a group, thanks to some divergence in activity in clinical trials which suggest there is still plenty to play for and—just possibly—that PD-1 is a better target than PD-L1 at least for some cancers. If that is the case, Sanofi and Regeneron could enter a more fragmented market with greater opportunity to make its mark versus its PD-1 rivals.

None of the current crop of PD-1/PD-L1 drugs have been approved to treat CSCC which is estimated to kill somewhere between 4,000 and 8,000 people in the U.S. each year. For patients diagnosed with advanced CSCC, there are limited treatment options and no standard of care.

At the American Society of Clinical Oncology (ASCO) meeting earlier this year Regeneron and Sanofi reported preliminary data from the first 26 subjects in a 400-patient phase 1 trial of cemiplimab in metastatic or inoperable CSCC, revealing an overall response rate of 46% including two complete responses.

The partners' other trials are in more competitive arenas, and include a phase 3 program ongoing for cemiplimab in non-small cell lung cancer and a phase 2 trial in basal cell carcinoma, another form of skin cancer. Early-stage experiments are also looking at pairing the drug with oncolytic virus therapies.

Sanofi and Regeneron are due to part ways on their longstanding antibody discovery alliance—which has generated several new drugs including arthritis treatment Kevzara (sarilumab), Dupixent (dupilumab) for atopic dermatitis and cholesterol drug Praluent (alirocumab)—at the end of the year.

Their collaboration still has some final candidates to bring forward however, including not only cemiplimab but also anti-IL-33 antibody REGN3500 for inflammatory diseases and REGN3767, an anti-LAG-3 antibody in development to treat cancer. A separate immuno-oncology collaboration with Sanofi is ongoing through at least 2020.