Fianlimab

With an FDA expansion as an adjuvant therapy for cutaneous squamous cell carcinoma patients who are at a high risk of recurrence after surgery and radiation, Regeneron's blockbuster Libtayo has gained five FDA approvals to treat skin and lung cancers. In 2022, Regeneron paid Sanofi $900 million to gain full rights to its partnered cancer drug Libtayo. Three years later, the pricey bet on the injected PD-1 inhibitor appears to be paying off.Thursday, the FDA approved Libtayo as the first immunotherapy for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC). The nod applies to patients who are at a high risk of recurrence after surgery and radiation.The green light comes seven years after Libtayo became the first drug to reach the market in CSCC, as it was endorsed for patients with metastatic CSCC or those with locally advanced CSCC who are not candidates for surgery or curative radiation.The patient population is significant; approximately 1.8 million are diagnosed annually in the U.S. with CSCC, accounting for roughly 20% of the nation's skin cancer cases.Regeneron has an application under review in Europe in the same indication, with a decision expected in the first half of 2026.“Patients whose CSCC is at a high risk of recurrence following surgery and radiation often have the poorest outcomes," Vishal Patel, M.D., professor of dermatology at George Washington University, said in a release. "Until now, we lacked options to help prevent a devastating recurrence and immunotherapy was only available for patients with advanced CSCC, who were no longer candidates for curative surgery or curative radiation."Patel added that the label expansion is “practice-changing” for the at-risk patient group. The approval was based on a phase 3 trial that showed Libtayo reduced the risk of disease recurrence or death by 68% compared to placebo at a median follow up of 24 weeks.Particularly noteworthy about the result was that Libtayo succeeded where Merck’s PD-1 powerhouse Keytruda had failed. A year ago, because of futility, Merck discontinued a trial of Keytruda as an adjuvant treatment for patients with high-risk locally advanced CSCC following surgery and radiation. Libtayo has been on a steady uptick in recent years. A few months after Regeneron secured sole possession of the medicine, the FDA signed off on a label expansion for Libtayo in combination with chemotherapy as a first-line treatment for advanced non-small cell lung cancer.Last year, Libtayo achieved blockbuster sales for the first time, generating $1.22 billion. Another increase is assured this year as second-quarter worldwide sales were up 27% year over year to $377 million. Regeneron also is studying Libtayo as a combo therapy with the company’s own fianlimab in first-line melanoma, where the regimen is going up against Keytruda.“If these data confirm best-in-class activity in melanoma, it will increase our confidence for this combination in other cancer settings,” Regeneron Chief Scientific Officer George Yancopoulos, M.D., Ph.D., said during the company’s second-quarter earnings call.

iStock, Deagreez Analysts at Truist Securities admitted that the result for itepekimab, which the companies were hoping to follow their blockbuster Dupixent in the I&I space, was “contrary to our expectations—we were wrong.” Sanofi and Regeneron’s Dupixent follow-up drug has failed to reach the sky-high expectations set by analysts for a pair of Phase III trials, sending the shares of both large pharmas down in early morning trading. Truist Securities analysts, which had predicted that the drug, called itepekimab, could have provided a wider patient population in COPD than Dupixent, said the new result was “contrary to our expectations—we were wrong.” The firm had predicted sales of $3.5 billion for the drug prior to the failed readout, but now it’s unlikely that itepekimab will receive approval without additional testing. BMO Capital Markets, meanwhile, said on Friday that the mixed result “muddies the water” for the candidate. Sanofi’s shares declined over 6% to $85.86 on Friday, while Regeneron tumbled a more dramatic 18% to $496.42, compared to $605.39 at Thursday’s close. The companies reported that itepekimab only met the primary goal in one out of two late-stage trials testing the interleukin-33 (IL-33) inhibitor in chronic obstructive pulmonary disease (COPD). The AERIFY-1 trial tested itepekimab in former smokers with inadequately controlled disease. This trial met the primary endpoint of significantly reducing moderate to severe exacerbations by 27% as compared to placebo at 52 weeks. The companies said this was a “clinically meaningful benefit.” AERIFY-2, however, did not meet the same goal, despite a benefit being observed earlier in the study. At week 52, patients who took itepekimab every two weeks had just a 2% reduction in exacerbations. This number jumped to 12% for patients dosed every four weeks but still did not meet the threshold of the primary endpoint. Truist said that in both studies, the total number of exacerbations was lower than expected, which “decreased the power” of both. BMO noted that the companies conducted the trial during the COVID-19 pandemic but had adjusted the study protocols to accommodate it. Big Shoes To Fill Both Sanofi and Regeneron had been hoping to raise itepekimab as a follow up to their blockbuster Dupixent, which brought in $14.15 billion worldwide last year—a 22% increase over the year prior. The drug has expanded into multiple indications in inflammatory diseases, most recently garnering an FDA nod for chronic spontaneous urticaria, or hives. While the companies still have about six years until Dupixent loses patent exclusivity, they have been hoping to find a replacement that could extend their winning streak. Itepekimab also provided a potential opportunity to expand the patient population addressed by Dupixent, which is currently only approved for type 2 COPD. Truist said in a note prior to Friday’s readout that itepekimab, which addresses airway inflammation “upstream” of Dupixent, could have addressed non-type 2 patients which make up about 60–70% of the 1.6 million patients with severe COPD. But the new drug would have needed to achieve a 20% reduction in exacerbations to set itself up for such an approval, according to Truist. Sanofi and Regeneron did not provide a plan for itepekimab’s future. The companies said they would review the data and discuss with regulatory authorities before announcing what’s next. BMO said that two positive Phase III trials are typically the standard for approval in COPD. In a Wednesday note prior to the readout, BMO said that Regeneron “has not been able to catch a break lately.” The company has been facing pressure from biosimilar competition to its approved medicines, regulatory rejections and “general malaise.” BMO had placed the likelihood of a “positive or a strong positive result” from the AERIFY trials at 80%. The firm considered a strong positive to be a reduction in exacerbations of 30% over background therapy, a result that could have driven broad use in former smokers with COPD. A negative result meanwhile “likely removes the opportunity for the asset in COPD.” “Today’s miss on significance adds to what has been a more difficult story for Regeneron in recent months,” BMO said Friday. “A statistically significant benefit in only one of the two Phase III trials leaves potential approval less likely for itepekimab.” BMO said Regeneron shareholders’ focus now turns to an upcoming readout for the PD-1/LAG3 melanoma combo of fianlimab and Libtayo, which is due in the second half. The company will also reveal some data on its obesity program in that timeframe.