EU to review Regeneron's bispecific odronextamab for B-cell malignancies

2023-08-17

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Regeneron Pharmaceuticals said Thursday that the European Medicines Agency (EMA) has agreed to review its marketing application for odronextamab, an investigational CD20xCD3 bispecific the company is seeking approval for to treat third-line adult patients with relapsed/refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL).

The filing contains results from the Phase I ELM-1 and pivotal Phase II ELM-2 trials presented late last year at the American Society of Hematology (ASH) annual meeting. The first of these is investigating odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy. ELM-2 includes more than 500 patients across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL).

Response rate over 80% in FL

Results from the ongoing ELM-2 study unveiled at the ASH meeting showed an overall response rate (ORR) of 82% in FL patients with Grades 1 to 3a disease, with 75% of the overall population achieving a complete response (CR). Data from the same trial, also presented at ASH, showed an ORR of 49% in heavily pre-treated DLBCL patients who were CAR-T-naïve, with 31% achieving a CR.

In 2020, Regeneron paused enrolment in odronextamab studies after being hit with a partial hold by the FDA, which requested that Regeneron amend trial protocols in order to mitigate the risk of cytokine release syndrome during step-up dosing.

Regeneron noted that its Phase III development programme for odronextamab, also known as REGN-1979, is evaluating the drug in earlier lines of therapy as well as additional B-NHLs. At its recent quarterly results presentation, company executives noted that dosing had been initiated for its CD22xCD28 costimulatory bispecifics with odronextamab in DLBCL, adding "we hope [we] can improve on the impressive efficacy demonstrated by odronextamab alone in that setting." Regeneron also noted during the earnings call that its US regulatory submission for odronextamab monotherapy for relapsed/refractory FL and DLBCL were "on track," although it did not give further details in its announcement Thursday.

Challenges ahead

Bispecifics recently approved for B-cell malignancies include Roche's Lunsumio (mosunetuzumab-axgb) and Columvi (glofitamab-gxbm) – both CD20xCD3 T-cell engagers – indicated for FL and DLBCL, respectively. Meanwhile, AbbVie/Genmab's Epkinly (epcoritamab-bysp), another CD20-directed CD3 T-cell engaging antibody CD20-directed CD3 T-cell engaging antibody, is approved for DLBCL, with recent data showing an ORR of 82% in third-line patients with relapsed or refractory FL.

Key opinion leaders (KOLs) interviewed for a new FirstWord report suggested that while Regeneron's odronextamab data has been impressive so far, it will likely struggle to gain ground from bispecifics that are ahead in development unless it can compete on price.

"The data in DLBCL doesn't look as good as with [Columvi] or [Epkinly], but the data in FL looks quite good," remarked one US-based KOL, adding "my best guess is odronextamab will have a tough time catching up in DLBCL; but I could see it finding a home in FL, although it will have to be as easy to give as [Lunsumio]." Another European KOL noted that odronextamab "has the same target as the others," but a potential positive of having three similar drugs on the market is that "the third drug could bring down cost. I'd like to see that," the KOL added.

For related analysis, see CAR-Ts, bispecifics and ADCs jockey for dominance in NHL.

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