More delays for Regeneron

Regeneron’s CD20-targeting T-cell engager odronextamab has been rejected again by the FDA, the company disclosed in its second-quarter earnings release on Friday. While previous CRLs in DLBCL and follicular lymphoma were triggered by insufficient confirmatory trial enrolment, the latest knockback, in follicular lymphoma only, was down to third-party manufacturing issues.

Meanwhile, a phase 3 readout for the group’s Lag3 contender fianlimab in first-line melanoma has been pushed back again, and now might not come until early 2026. Regeneron blamed a slowing in the rate of progression-free survival events.

Third time unlucky

Odronextamab had been due an FDA decision by 30 July, but that date came and went without any word, leaving investors fearing the worst. On 1 August, Regeneron disclosed that the project had indeed been rejected, due to issues raised during an FDA inspection of a Catalent facility in mid-July. The problems have also hit Regeneron’s eye drug Eylea.

Catalent was acquired by Novo Nordisk last year, and the Danish company expects to respond to the FDA this week, according to Regeneron.

This might not be fatal for odronextamab, but it’s another embarrassing regulatory development for Regeneron, following CRLs for both the CD20 project and its BCMA-targeting T-cell engager Lynozyfic last year. The latter has since got FDA accelerated approval for late-line multiple myeloma.

Although Regeneron’s recent focus for odronextamab has been on follicular lymphoma, the group apparently still has hopes in the more aggressive DLBCL, with several phase 3 trials ongoing.

Phase 3 trials of odronextamab

Source: OncologyPipeline.

More Lag3 lags

Meanwhile, investors could be waiting a bit longer for the first pivotal data with fianlimab. The first-line melanoma trial in question compares a Libtayo combo versus Merck & Co’s Keytruda.

Data had once been expected in 2024, but last year were pushed back to the second half of 2025. Now they’re set for the end of this year or early 2026.

Some Regeneron backers might hope that the slowing event rate is a good sign, as it could mean that fianlimab plus Libtayo is delaying disease progression. However, it’s also possible that the Keytruda arm is seeing few events, too.

In first-line melanoma, Regeneron is also testing a fianlimab/Libtayo fixed-dose combination, versus Bristol Myers Squibb’s Opdualag. Enrolment here is still ongoing, according to Regeneron’s second-quarter presentation.

And in first-line NSCLC, phase 2 results from two phase 2/3 trials, once expected last year, still haven’t emerged. As disclosed in Regeneron’s first-quarter earnings call, pre-planned interim analyses were conducted in May, but due to limited follow-up the studies continued. The next analyses will take place in early 2026, and the company will then decide whether to advance into phase 3.

Late-stage trials of fianlimab

Note: *phase 2/3. Source: OncologyPipeline.