A new FDA filing for the PD-1 checkpoint inhibitor cemiplimab now underway represents more than simple progress for Regeneron Pharmaceuticals Inc. and Sanofi SA. The filing, supported by top-line results from a pivotal phase II trial in the world's second most deadly skin cancer, could lead to approval for a drug key to realizing strategic goals at both companies.

The results of the study, called EMPOWER-CSCC 1, were clear for the 82 patients with advanced cutaneous squamous cell carcinoma (CSCC) who enrolled. Those participants, part of a small subset of people with CSCC for whom neither surgery nor, in many cases, systemic chemotherapy or radiation helped, saw an overall response rate to cemiplimab of 46.3 percent, a measure confirming almost exactly the results of an earlier phase I expansion study. The median duration of response in the study hasn't yet been reached.

The rolling biologics license application for the candidate, now in motion, is expected to be completed in the first quarter of 2018. If approved, Regeneron and Sanofi will equally split worldwide profits on its sale.

Enrollment in EMPOWER-CSCC 1 continues in the remaining two study arms of patients with metastatic CSCC receiving a 350-mg flat dose of cemiplimab every three weeks and patients with locally advanced and unresectable CSCC receiving a 3-mg/kg dose of cemiplimab every two weeks. Updated results from all parts of the phase II and the phase I trial will be submitted for presentation at a 2018 medical congress, the companies said.

Israel Lowy, Regeneron's vice president of global clinical development and head of translational science and clinical oncology, told BioWorld that Regeneron decided to develop its own PD-1 "because we recognized that it's a foundational component of any credible immunotherapy program." It reached an agreement to advance the agent with Sanofi in July 2015 as part of a deal that included an up-front payment to Regeneron of $640 million, part of an immuno-oncology pact valued at the time to include up to $2.2 billion in total investments. (See BioWorld Today, July 29, 2015.)

Developing an in-house PD-1 is important to Regeneron "not because we think we can necessarily make a better PD-1, but because having our own PD-1 gives us enormous flexibility and the opportunity to pursue many different combinations," Lowy said. "Regeneron has been working very hard to generate a really impressive portfolio of home-grown therapeutic candidates that we want to test in combination. If we identify a really potent one, we want to be unconstrained with how we choose to develop and commercialize it."

Cemiplimab, which gained FDA breakthrough status in September, has so far proved to have a safety profile in the study and was generally consistent with approved anti-PD-1 agents, Regeneron reported. The new regulatory filing, due to be joined by a completed submission to the EMA in the first quarter of 2018, is one of nine Sanofi expects to make over the next 18 months.

"The PD-1 program is going to get quite broad and it's going to provide the underpinnings for many other agents that we bring forward," Lowy said — an observation that seems like a modest understatement in light of the trials underway and planned.

Beyond the CSCC program, Regeneron and Sanofi have numerous other registration-directed programs, including one in advanced basal cell carcinoma and another in recurrent and metastatic cervical cancer. It's also exploring applications of the candidate in first-line lung cancer for patients with high PD-L1 – "to see if we can beat chemotherapy in that setting in areas of the world where pembrolizumab is not available," he said – and in recurrent metastatic head and neck cancer and melanoma. And that's just the monotherapy studies.

Combinations studies currently in phase I include a test of cemiplimab with REGN-1979, a bispecific fully human antibody targeting CD20 and CD3, for the treatment of B-cell non-Hodgkin lymphoma; there's also a combination with REGN-3767, an antibody to lymphocyte-activation gene 3, for the treatment of advanced solid tumors and lymphoma. Cemiplimab is also being testing in a phase Ia/IIb trial with Inovio Pharmaceuticals Inc.'s INO-5401 T-cell-activating immunotherapy, and INO-9012, an immune activator encoding IL-12, for the potential treatment of patients with newly diagnosed glioblastoma; and with Sillajen Inc.'s Pexa-Vec for the potential treatment of metastatic or unresectable renal cell carcinoma.

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