Regeneron’s lung cancer Lag3 lag
Fianlimab NSCLC data are delayed, while odronextamab gets a DLBCL blow.
Fianlimab NSCLC data are delayed, while odronextamab gets a DLBCL blow.
Regeneron is already behind its big Lag3 rivals, and the company had bad news this week with a delay to its hopeful fianlimab in first-line NSCLC. Two phase 2/3 studies had been due to yield phase 2 data by the end of 2024, but Regeneron said in its JP Morgan presentation that the results would now come in the first half of 2025.
There was also a mixed update for the group’s T-cell engagers, which were knocked back by the FDA last year. Linvoseltamab is already refiled; however, while Regeneron is also planning a resubmission soon for odronextamab, this will only include follicular lymphoma, and not the more important setting of DLBCL. A spokesperson told ApexOnco that the group was continuing to evaluate its refiling plans in the latter.
Selected upcoming Regeneron oncology milestones
| Project | Description | Event | Timing | Note |
|---|---|---|---|---|
| Odronextamab | Anti-CD20 T-cell engager | BLA resubmission in 3rd-line+ FL | Q1 2025 | CRL in r/r FL & DLBCL Mar 2024; enrolment into confirmatory study under way |
| Linvoseltamab | Anti-BMCA T-cell engager | FDA approval in 3rd-line+ MM | Mid-2025 | CRL in r/r MM Aug 2024 (manufacturing issues); BLA “recently” resubmitted |
| Fianlimab | Anti-Lag3 MAb | Ph2 data in NSCLC, + Libtayo +/- chemo | H1 2025 | Had been expected in H2 2024 |
| Ph3 data in 1st-line melanoma, + Libtayo vs Keytruda | H2 2025 | Had once been expected in H2 2024 |
Source: company presentation.
Lag3 projects have disappointed in NSCLC, although this hasn’t stopped Bristol Myers Squibb from pushing into phase 3 with Opdualag.
Regeneron reckons that it has both a better Lag3, as well as a better PD-1 inhibitor in Libtayo. This, it believes, might give it a better chance of success. But investors will now have to wait a little longer for the big reveal.
One first-line NSCLC study combines fianlimab with Libtayo in PD-L1-high patients, while the other is evaluating fianlimab plus Libtayo and chemo in PD-L1 all-comers. The phase 2 portions have ORR as their primary endpoints; if the trials progress to their phase 3 portions, overall survival will become the main focus.
At least pivotal data with fianlimab in first-line melanoma, potentially its first approved use, continue to be expected in the second half – although these had once also been due in 2024.
Refiling
Regeneron’s twin T-cell engager blows last year came with CRLs for the BMCA-targeting linvoseltamab (on third-party manufacturing issues) and the CD20-targeting odronextamab, rejected because its confirmatory trials were still in their dose-finding stages.
Now linvoseltamab has been resubmitted in relapsed/refractory multiple myeloma, with an FDA decision expected by mid-2025.
Meanwhile, odronextamab is set for refiling in the first quarter. However, a closer look at Regeneron’s JP Morgan presentation shows that this is only planned in relapsed/refractory follicular lymphoma, despite the company having previously also sought approval in diffuse large B-cell lymphoma.
A spokesperson for Regeneron told ApexOnco that “in DLBCL, we’re continuing to evaluate our US resubmission plans against enrolment in the confirmatory trial”. This might be a reference to the difficulty of enrolling patients into such a trial at a time when Columvi and Epkinly are already approved.
Libtayo
The company had better news with Libtayo, which prevailed in adjuvant cutaneous squamous cell carcinoma in the phase 3 C-Post trial. The study found a 68% reduction in the risk of disease recurrence or death versus placebo; Regeneron plans an FDA filing in the first half of 2025.
The company noted that Keytruda recently failed in this setting, in Keynote-630. Still, Libtayo sold $869m in 2023, versus Keytruda’s $25bn.
154
