Catching up with Keytruda, Regeneron scores frontline NSCLC approval for Libtayo/chemo combo

Regeneron’s Libtayo has made it into the exclusive club of PD-(L) inhibitors approved, in combination with chemotherapy, as a frontline treatment for a broad swath of lung cancer patients.

Based on Phase III overall survival data, the FDA granted Libtayo an approval for the first-line treatment of adult patients with advanced non-small cell lung cancer with no EGFR, ALK or ROS1 aberrations.

Israel Lowy

“Libtayo is now approved for extending the survival of patients with advanced non-small cell lung cancer as both a monotherapy in high PD-L1 expressors and in combination with chemotherapy irrespective of PD-L1 expression levels, achieving a high bar that has only been met by one other PD-1 targeting agent,” said Israel Lowy, SVP, translational and clinical sciences, oncology at Regeneron.

He didn’t name it, but that other PD-1 targeting agent is Keytruda, Merck’s dominating multibillion-dollar checkpoint drug.

While other PD-(L)1 blockers, such as Bristol Myers Squibb’s Opdivo, AstraZeneca’s Imfinzi and Roche’s Tecentriq, are all approved in some NSCLC patient groups, they are either not available as monotherapy in the frontline setting, limited to subpopulations or combined with other drugs in addition to chemo.

Tyler Van Buren

Cowen analyst Tyler Van Buren noted that the approval, which had been delayed from a September decision date due to a site inspection, was widely expected, given positive Phase III data. Compared to Libtayo’s previous approval in a subset of patients, the new OK unlocks a broader market, as an estimated 70% of frontline metastatic NSCLC patients have low PD-L1 expression.

“With that said, there is a high level of skepticism that Libtayo + chemo will make a dent in the 1L NSCLC treatment paradigm relative to Keytruda + chemo, so we expect investors to take a wait-and-see approach before ascribing value,” he wrote.

In the Phase III EMPOWER-Lung-3 trial, the Libtayo/chemo combo helped patients live much longer than chemo alone, with a median OS of 22 months versus 13 months — translating to a 29% lower risk of death (p=0.014). Adding Libtayo also extended progression-free survival and the duration of response, as well as boosting the overall response rate. The trial enrolled 466 patients.

The safety warnings on the updated label are in line with the checkpoint class, Van Buren added, with alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy and decreased appetite as the most common adverse reactions. Serious adverse events occurred in 25% of patients; 5% discontinued due to side effects and 6% died.

“Of note, the incidence and severity of immune-related adverse events (for which a warning appears on the label) were similar between monotherapy and in combination with chemo and among different age groups,” he wrote.

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