- Regeneron Pharmaceuticals Inc. and Sanofi SA's plan to break into the increasingly competitive immuno-oncology market advanced a step forward Wednesday, when the New York-based biotech reported positive clinical results for its PD-1 inhibitor cemiplimab in a type of skin cancer.
- In a Phase 2 trial, 46% of patients with cutaneous squamous cell carcinoma (CSCC) responded to treatment with cemiplimab. Median duration of response had not yet been reached through a minimum follow-up of six months.
- Regeneron's study is open-label and only enrolled patients into a single treatment arm. Still, no therapies are currently approved to treat advanced CSCC and Regeneron has begun submitting the data to the Food and Drug Administration on a rolling basis.
If Regeneron and Sanofi are successful in winning U.S. approval of cemiplimab, the monoclonal antibody would be the sixth PD-1/L1 blockers to enter the market, a logjam of pharmaceutical investment that has made the promising class hyper-competitive.
Already two such checkpoint inhibitors, Merck & Co.'s Keytruda (pembrolizumab) and Bristol-Myers Squibb Co.'s Opdivo (nivolumab), have broached the lofty mark of $1 billion in sales per quarter.
Yet Regeneron believes cemiplimab can stand apart. Part of that planned differentiation will come through the clinical development path the biotech and Sanofi have laid out. By first targeting CSCC, the companies aim to win approval for an indication with no therapies approved by the Food and Drug Administration for patients who can't be cured with surgery or radiation.
In some ways this mimics the strategy of Pfizer Inc., which first developed its checkpoint inhibitor Bavencio (avelumab) for Merkel cell carcinoma (MCC), a market that front-runners Keytruda and Opdivo hadn't yet entered. A rare form of skin cancer, MCC is diagnosed in roughly 1,600 U.S. patients each year.
Regeneron and Sanofi, however, will be targeting what they claim is the second deadliest skin cancer after melanoma. According to numbers compiled by Sanofi in a recent corporate presentation, 5,000 to 13,000 cases of metastatic or locally advanced CSCC are diagnosed each year and between 3,900 and 8,700 people die.
While targeting CSCC may be an easier entry point into the immuno-oncology market, Regeneron and Sanofi also believe cemiplimab will be more competitive broadly due to the way the drug inhibits the PD-1/L1 pathway.
Keytruda and Opdivo both block the PD-1 receptor, which is expressed on T cells, while the three other checkpoint inhibitors block the PD-L1 ligand, expressed within tumors.
"I think in the end anti-PD-1 will prove superior to anti-PD-L1 due to basic biologic principles," explained Israel Lowy, head of translational science and clinical oncology at Regeneron, in a recent interview.
Lowy cautioned that the science still isn't settled, but hypothesized that the PD-1 receptor could be easier to access by antibody-based drugs than PD-L1. Targeting PD-1 also blocks PD-L2, a related ligand that has been less studied than its counterpart PD-L1.
Regardless of biology, however, Regeneron and Sanofi will still face an uphill battle. CSCC may be less competitive than other indications, but to deliver the financial returns the companies likely expect, they will have to venture into more contested areas, such as lung cancer.
"The story in lung cancer is far from settled," Lowy said, referring to the see-saw competitive balance between Opdivo and Keytruda as well as a still-unsettled picture on how combinations could improve on monotherapy.
A Phase 3 study in frontline non-small cell lung cancer (NSCLC) is currently enrolling, pitting cemiplimab against platinum chemotherapy in patients with greater than or equal to 50% PD-L1 expression. Other studies testing cemiplimab combinations in first-line NSCLC are planned or just beginning.
Greater freedom to pursue combinations also factored into Sanofi and Regeneron's decision to develop a checkpoint inhibitor, Lowy explained. By developing their own PD-1, the companies are less constrained by the profile and cost of a competitor's drug.
All that is well and good. Yet five other companies are pursuing similar strategies and are already on market with their own backbone. Regeneron and Sanofi will have to deliver clear superiority in monotherapy or in combinations to leapfrog their rivals in the larger and more financially lucrative indications.