Current Edition

Regeneron’s Libtayo finally scores Keytruda-matching FDA nod in newly diagnosed lung cancer. Can it catch up?

After weeks of an inspection-related delay, Regeneron has finally won a much-anticipated FDA approval for Libtayo in newly diagnosed non-small cell lung cancer (NSCLC), opening another front to challenge Merck & Co.’s formidable Keytruda.

In a win for Regeneron, the new nod clears Libtayo along with chemotherapy in a broad first-line NSCLC population. It doesn’t limit Libtayo’s use to any specific cancer histology or by tumor PD-L1 expression status.

Libtayo’s price will stay the same, a Regeneron media aide told Fierce Pharma. A similar application is also under review at the European Medicines Agency, and a decision is expected in the coming month, according to the company.

The go-ahead makes Libtayo now the only other PD-1/L1 inhibitor besides Keytruda that boasts a U.S. chemo combo use in first-line NSCLC regardless of PD-L1 levels or histology, adding to a previous monotherapy approval for PD-L1-high expressers. But a Keytruda-matching indication doesn’t necessarily mean Libtayo could just split the market with the Merck PD-1 king.

For starters, Libtayo’s data aren’t differentiated. Libtayo’s combination with chemo cut the risk of death by 29% over chemo alone in the EMPOWER-Lung 3 trial. In a subgroup of patients with squamous cell carcinoma, Libtayo does appear to hold an advantage over Keytruda by cross-trial comparison. The Regeneron drug cut the risk of death by 44% in this population, versus 29% for Keytruda in a final analysis of the KEYNOTE-407 trial.

But Libtayo performed worse in the non-squamous subgroup with a death risk reduction of 21% in EMPOWER-Lung 3, whereas Keytruda is well known for its roughly 50% reduction in KEYNOTE-189. Between the two subtypes of NSCLC, non-squamous is the larger one, with about 70% representation of all cases.

Before Libtayo’s new FDA approval came through—after a short delay—doubts had also circled around whether the agency would exclude the PD-L1-negative population. In EMPOWER-Lung 3, Libatyo’s addition to chemo showed no death risk reduction in PD-L1 non-expressers. Regeneron used a more sensitive diagnostic to measure PD-L1 and therefore has probably identified PD-L1-negative cases by a more stringent criterion, the company has argued.

While Libtayo’s clinical data are mostly similar if not worse than Keytruda’s, SVB Securities analyst Daina Graybosch, Ph.D., had previously noted that the Libtayo-chemo regimen’s duration of response, at a median 15.6 months, is the longest seen among all major front-line NSCLC trials of PD-1/L1 inhibitors.

“If I were them, I would really focus on that,” Graybosch said in an interview with Fierce Pharma after Regeneron shared detailed EMPOWER-Lung 3 results last September.

Without a clear efficacy edge, Libtayo will have a difficult time luring doctors away from Keytruda, which has long established itself as the standard of care in newly diagnosed NSCLC. Graybosch at that time projected Libtayo’s share in all lines of metastatic NSCLC will never exceed 5% within the PD-1/L1 class.

Currently, with FDA approvals in certain skin cancers and as a single agent in PD-L1-high NSCLC, Libtayo only sold $126 million in the third quarter globally, not even close to the $5.4 billion in sales posted by Keytruda during the same period. Sanofi also recently backed out of the Libtayo collaboration amid regulators’ review of the chemo combo front-line NSCLC indication.

And Libtayo has had its fair share of setbacks in its confrontation with Keytruda. Regeneron in January pulled a Libtayo application in second-line cervical cancer shortly after Keytruda chalked up a first-line approval.

Libtayo’s front-line NSCLC approval may as well be the last one without any head-to-head data against Keytruda. The FDA earlier this year shot down Eli Lilly and Innovent Biologics’ Tyvyt in front-line NSCLC partly because the drug’s phase 3 compared the China-made PD-1 to chemo, which the FDA said is an outdated treatment. More recently, following discussions with the FDA, Gilead Sciences and Arcus Biosciences adjusted a PD-1/TIGIT combo phase 3 of zimberelimab and domvanalimab to pit that regimen against Keytruda, instead of chemo, in PD-L1-high NSCLC.