Sanofi and Regeneron’s Libtayo is on a roll with its second FDA nod in just two weeks. And the latest green light breaks the PD-1 inhibitor out of its skin cancer comfort zone and into the competitive—and lucrative—lung cancer market, where Merck & Co.’s Keytruda reigns supreme.
Libtayo won an FDA go-ahead Monday to treat patients with newly diagnosed, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have high levels of PD-L1 expression.
It’s the third OK for Libtayo, following two in certain types of skin cancer. It moves the drug an important step toward the blockbuster sales mark. But thanks to a competitive landscape—dominated by Keytruda—SVB Leerink analyst Geoffrey Porges has predicted less than $1 billion in Libtayo lung cancer sales at peak, though he acknowledged a future combo regimen might have a better shot at grabbing market share.
Just how could Libtayo compete with Keytruda? It’s complicated.
In its FDA-approved PD-L1-high patient population, Libtayo cut the risk of death by 43% over chemotherapy in a phase 3 trial dubbed Empower-Lung 1. Libtayo hit that result in a subset of enrolled patients after problems with a PD-L1 diagnostic test forced a mid-trial switch.
Regeneron and Sanofi say the analysis covered patients with “proven” PD-L1 expression of 50% or more. However, the 43% benefit isn’t featured in the drug’s updated FDA label (PDF), only on the new label of the FDA-approved PD-L1 test kit. The number on Libtayo’s label, which counts all randomized participants, has the death risk reduction at 32%.
Merck's PD-1 king has two sets of phase 3 monotherapy data. After long-term follow-up in the Keynote-024 trial, Keytruda slashed the risk of death by 38% over chemo among patients with a PD-L1 proportion score of 50% or greater. In the Keynote-042 trial, the drug cut that risk by 31% in the same patient group.
Based on those numbers, analysts figure Libtayo won’t be able to shake Keytruda’s market lead. “[N]one of the results for Empower give Regeneron and Sanofi any promotional leverage against Merck’s juggernaut brand,” Porges wrote in a September note to investors.
But Regeneron and Sanofi have been pointing to some unique features of the Empower trial as advantages for Libtayo. For example, 74% of patients in the chemo arm crossed over to receive Libtayo after tumor progression—a high percentage for such trials. That crossover likely tipped the overall survival data in favor of chemo, the companies say. The trial also included patients with stable brain metastases, who usually have a poorer prognosis than those without brain metastases.
“This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice,” Naiyer Rizvi, M.D., which helped run the Empower study, said in a statement Monday.
Overall, the Street’s consensus estimates suggest that Libtayo’s 2021 sales would represent about 5% of the $8 billion-plus PD-1/L1 market in NSCLC, Porges said in a note Tuesday.
Solo immuno-oncology agents are now only offered to patients who can’t tolerate chemo. Instead, the standard of care has switched to the combination of Keytruda and chemotherapy, which is known for its impressive 50% reduction in death risk over solo chemo.
Regeneron and Sanofi do have their own Libtayo combinations in front-line NSCLC testing. The phase 3 Empower-Lung 3 study explores a pairing of Libtayo and chemotherapy with or without Bristol Myers Squibb’s CTLA4 inhibitor Yervoy. A planned interim analysis will happen later this year to determine whether the trial has met its goal.
In his note, Porges argued that this pivotal trial—especially the subgroup analysis of PD-L1-low NSCLC with less than 50% expression—“may have a larger impact as positive results could open up a larger patient population than the PD-L1-high approval enables.”
Libtayo nabbed its first FDA green light in 2018 for advanced cutaneous squamous cell carcinoma. Two weeks ago, it added basal cell carcinoma to its label. It raked in sales of about $348 million in 2020 after an 80% year-over-year growth.