Nivolumab/Relatlimab

Regeneron Pharmaceuticals’ LAG-3 inhibitor called fianlimab has flunked a late-stage skin cancer trial, marking yet another blow for the drug class. The announcement follows a spate of recent clinical setbacks for candidates targeting the LAG-3 immune checkpoint. In March, Immutep’s eftilagimod alfa failed a Phase 3 lung cancer study. In February 2025, Bristol Myers Squibb’s fixed-dose combination of LAG-3 and PD-1 targeting drugs, known as Opdualag, failed in its bid to expand into the adjuvant setting in melanoma. Regeneron’s Phase 3 study is in first-line unresectable locally advanced or metastatic disease, and enrolled over 1,500 patients. Fianlimab, combined with the PD-1 inhibitor Libtayo, missed the trial’s progression-free survival primary endpoint. Jefferies analysts had only earmarked around $321 million in first-line melanoma peak sales for fianlimab. Even so, Regeneron’s $REGN stock was down about 10% premarket on Monday. If it had been successful, the fianlimab-Libtayo combo could have posed competition for Opdualag, which is the only LAG-3 drug approved for first-line melanoma. The high-dose fianlimab combination regimen produced an average 11.5-month PFS, while the low-dose regimen led to a 9.6-month PFS, according to Regeneron’s Friday release . While both of these figures were numerically higher than the average 6.4-month PFS achieved by Keytruda monotherapy in the study, neither was statistically significant. Regeneron plans to present full results from the trial at a future medical meeting. The drugmaker is still running two other Phase 3 melanoma studies of its fianlimab-Libtayo combo: one testing the regimen head-to-head against Opdualag in first-line disease and another against Keytruda in the adjuvant setting where patients have had their cancer surgically removed. That second study is closely watched as Opdualag failed in the same setting early last year. It is expected to have primary endpoint data in 2028, according to ClinicalTrials.gov. Opdualag has faced its share of clinical disappointments. Besides the miss in adjuvant melanoma, its positive mid-stage data in lung cancer drew skepticism in 2024 for relying on an analysis described as “cherry-picked.” Meanwhile, other drugmakers are exiting the LAG-3 space entirely. In 2024, Merck and Incyte shuttered their respective programs.

Dive Brief:An experimental cancer immunotherapy from Regeneron failed a late-stage study in melanoma in a surprise setback for the big biotechnology companys oncology business.A regimen involving the prospect, fianlimab, and Regenerons marketed medicine Libtayo didnt significantly delay cancer progression compared to Merck & Co.s Keytruda in patients with unresectable metastatic melanoma. A high-dose combination held tumors in check for a median of 11.5 months, compared to 6.4 months for Keytruda recipients, a difference that narrowly missed statistical significance.Regeneron didnt provide additional details but will present them at a future medical meeting. Another Phase 3 study testing fianlimab against Opdualag, a similar cancer immunotherapy sold by Bristol Myers Squibb, is ongoing. Company shares fell by double digits early Monday, erasing billions of dollars in market value.Dive Insight:Regeneron is one of the biopharmaceutical sectors most valuable companies thanks to the runaway success of the eye drug Eylea and the anti-inflammatory medicine Dupixent. But its facing gnawing investor questions about whats next. A high-dose version of Eylea hasnt been selling as quickly as Wall Street had hoped, and multiple research setbacks and manufacturing-related delays have heightened pressure on the companys pipeline to deliver.Oncology is one area Regeneron has long looked to for future growth. The company has two cancer drugs approved, and one of them, the immunotherapy Libtayo, now generates more than $1 billion in annual sales. The hope has been that fianlimab, a different kind of immunotherapy, might elevate that figure even higher as a complementary treatment that could amplify Libtayos effects.Fianlimab is aimed at a protein, LAG-3, thats long been pursued by drugmakers as an immunotherapy target despite mixed clinical results. Earlier this month, Regeneron reported that Phase 2 results in lung cancer didnt support further development. But Bristol Myers similar medicine, Opdualag, succeeded in melanoma, leading Wall Street analysts to expect fianlimab might similarly come through in a big Phase 3 study in the same indication. Analysts at RBC Capital Markets have estimated that positive results would yield a market opportunity worth anywhere from $1.6 billion to $1.8 billion.The setback announced Friday, then, comes as a disappointment as most had expected [fianlimab] to work, wrote RBCs Brian Abrahams in a Sunday research note. The failure could cause skeptics to more vocally question the companys overall direction and strategy, Abrahams wrote.Regeneron has late-stage studies underway for a new kind of blood thinner, and important pivotal tests are ongoing for other drugs in myeloma, obesity and certain immunological conditions. Yet the targets for many of those therapies are also being pursued by others, leading to some grumbling as to whether the company should be focusing on more novel concepts or a different mix of low- and high-risk programs, Abrahams added.A handful of Eylea biosimilars could launch later this year, too, which could further depress Regenerons core franchise, wrote Leerink Partners David Risinger.We hope management will pursue external business development opportunities to enhance the companys long-term growth outlook, Risinger wrote. '