Regeneron shoots again with odronextamab
The company hits an FDA-mandated enrolment target, but only in follicular lymphoma.
The company hits an FDA-mandated enrolment target, but only in follicular lymphoma.
Regeneron is taking another shot at the FDA with its troubled CD20-targeting T-cell engager odronextamab, following a complete response letter last year. But, as previously reported by ApexOnco, the refiling is only in relapsed/refractory follicular lymphoma; Regeneron had originally also sought approval in relapsed DLBCL.
In January, the group told ApexOnco that it was still evaluating its US resubmission plans “against enrolment in the confirmatory trial”. This raised the possibility that recruitment into the phase 3 DLBCL study, Olympia-3, was proving troublesome; AbbVie/Genmab’s Epkinly and Roche’s Columvi already have accelerated nods here, and Columvi might soon have full approval, with a decision on the phase 3 Starglo trial expected by July.
If Columvi gets the full nod this could call into question the availability of an accelerated pathway for odronextamab. Epkinly also appears to have stalled, with readout of its confirmatory Epcore DLBCL-1 trial being delayed until 2026; results had previously been expected in 2024, itself a delay from 2023.
In follicular lymphoma, where odronextamab has a PDUFA date of 30 July, Regeneron is apparently seeing demand: the company disclosed on Wednesday that it had hit an FDA-mandated enrolment target in the confirmatory Olympia-1 study.
Regeneron added that this was the “sole approvability issue” identified by the FDA in its March 2024 complete response letter – at the time, the group said only that the agency had questioned the status of its confirmatory trials, without pinpointing any study in particular.
Regeneron-sponsored phase 3 trials of odronextamab
| Trial | Setting | Includes dose finding? | First posted | Status |
|---|---|---|---|---|
| Olympia-1 (confirmatory) | vs Rituxan + chemo in 1L FL | Yes | Oct 2023 | Safety lead-in data at ASH 2024: 12/12 CRs, Gr≥3 TEAEs in 5/13 pts; FDA-mandated enrolment target achieved; completes Apr 2029 |
| Olympia-2 | + chemo, vs Rituxan + chemo in 1L FL | Yes | Oct 2023 | Completes Jul 2029 (from Jan 2030) |
| Olympia-3 | + chemo, vs Rituxan + chemo in 1L DLBCL | Yes | Oct 2023 | Completes Sep 2028 |
| Olympia-4 | vs SoC in r/r B-cell NHL | No | Jan 2024 | Completes May 2027 (from Jul 2027) |
| Olympia-5 | + Revlimid, vs Rituxan + Revlimid in r/r FL & MZL | Yes | Nov 2023 | Completes Jan 2029 (from Oct 2029) |
Notes: DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; MZL=marginal zone lymphoma; NHL=non-Hodgkin lymphoma. Source: OncologyPipeline & clinicaltrials.gov.
Regeneron didn’t disclose the FDA-requested target for Olympia-1, but said during its fourth-quarter earnings call that the trial was over 40% enrolled.
The study, in first-line follicular lymphoma, consists of an initial uncontrolled safety lead-in portion, while the second part will test odronextamab monotherapy versus Rituxan plus chemo.
The company reported safety lead-in data at last year’s ASH meeting, showing a 100% complete response rate among 12 patients. However, toxicity has always been the main question for odronextamab – and in Olympia-1, five of 13 safety-evaluable patients had grade 3 or higher treatment-emergent adverse events.
Among these, two patients experienced liver enzyme elevations, and one patient discontinued the study prematurely because of these. Despite this, the ASH abstract noted that no patients experienced dose-limiting toxicity.
Any concerns haven’t put off the EU regulator: the EMA greenlit odronextamab, as Ordspono, last July.
Odronextamab isn’t Regeneron’s only T-cell engager to have problems: the group also got a CRL for its BCMA-targeting project linvoseltamab, although that seemed less critical, being down to third-party manufacturing issues. That project was also recently refiled, and a decision is expected by 10 July.
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