Another LAG-3 setback as Regeneron drug fails phase 3 trial

Regeneron has reported that its fianlimab antibody targeting LAG-3, an immune checkpoint proposed as a cancer target, has missed the mark in a highly anticipated melanoma trial.

The phase 3 trial was evaluating two doses of anti-LAG-3 antibody fianlimab in combination with PD-1 inhibitor Libtayo (cemiplimab) as a first-line treatment in more than 1,500 patients with unresectable locally advanced or metastatic melanoma, comparing the regimen to monotherapy with MSD's widely-used PD-1 drug Keytruda (pembrolizumab).

In a statement, Regeneron revealed that the combination was unable to show a statistically significant improvement in median progression-free survival (PFS) compared to Keytruda, although, there was a numerical extension of 5.1 months with the highest dose – 11.5 months versus 6.4 months – which was not far off the threshold for significance.

Bristol Myers Squibb is the only drugmaker so far to have brought a drug in the LAG-3 class to market – Opdualag – which combines LAG-3 drug relatlimab with its PD-1 inhibitor Opdivo (nivolumab) and was approved in 2022 for unresectable or metastatic melanoma.

Since then, BMS has been plagued by a series of clinical trial failures in indications like adjuvant treatment of melanoma and metastatic colorectal cancer, preventing it from extending the drug's label, although, it has still been growing quite strongly and topped $1 billion in global sales last year.

Regeneron still has at least one shot on goal left with fianlimab in melanoma – a head-to-head study comparing the high-dose combination with Opdualag in first-line unresectable or metastatic melanoma – which is due to generate results next year.

The challenge for the company will be trying to build a case for fianlimab/cemiplimab as an alternative to Opdualag in melanoma when the drug has failed to improve on PD-1-targeted monotherapy.

Meanwhile, Regeneron has also reported disappointing results with fianlimab in front-line non-small cell lung cancer (NSCLC) treatment, abandoning that indication after a phase 2 fail.

There have been other failed trials with LAG-3 contenders from other companies as well, such as Immutep's eftilagimod alfa, dropped for first-line NSCLC in combination with Keytruda and chemo after a phase 3 readout earlier this year, as well as MSD's candidate favezelimab, which was abandoned in 2024 after failed trials in lung and colorectal cancers.

Shares in Regeneron have lost almost 12% of their value in pre-market trading following the fianlimab announcement, reflecting the diminished prospects for a drug that has previously been tipped to become a $2 billion-plus brand.