The FDA has turned down a pair of marketing applications for Regeneron’s CD20xCD3 bispecific antibody odronextamab to treat two common forms of non-Hodgkin lymphoma (NHL).
The decision throws a spanner into Regeneron’s plans for a strong launch of the drug in the NHL market, with a label that would be the broadest of any drug in the class.
The company had filed for approval of odronextamab to treat adults with relapsed/refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have progressed after at least two prior systemic therapies, but both applications resulted in complete response letters (CRLs) from the US regulator.
There are three CD20xCD3 bispecifics already on the US market, but so far all are approved with narrower labels.
Roche’s first-to-market Lunsumio (mosunetuzumab) is currently indicated as a third-line or later therapy for FL, while stablemate Columvi (glofitamab) can be used to treat DLBCL or large B-cell lymphoma (LBCL) arising from FL, also after two lines of prior therapy.
AbbVie/Genmab’s Epkinly (epcoritamab), meanwhile, is labelled for use in DLBCL patients after two or more systemic therapies, but has also been submitted as a third-line therapy for FL, with a decision due by 28th June.
Regeneron attempted to downplay the CRLs in a statement, saying that the issue cited in the letters related to the enrolment status of trials that would be used to confirm accelerated approvals for the two indications.
The CRLs “did not identify any approvability issues with the odronextamab clinical efficacy or safety, trial design, labelling, or manufacturing,” it added.
Explaining the problem, Regeneron said the OLYMPIA programme of trials are exploring the use of odronextamab in various types of NHL, as well as in earlier lines of therapy, and have been designed with both dose-finding and confirmatory portions.
The dose-finding stage of the trials is already underway, but the FDA wants the confirmatory stages to also be underway, with timelines agreed for the completion of the studies. This is something the regulator has become particularly keen on as part of a general clampdown on the requirements for accelerated approvals for new medicines.
In its Project Confirm initiative, the FDA states that it “strongly recommends that the confirmatory trial(s) be well underway if not fully enrolled at the time of accelerated approval,” and the latest decision marks a firming up of that position.
Regeneron hasn’t said when it will be able to resubmit the dossier, indicating that it will provide an update “later this year”. Odronextamab is also under regulatory review in Europe.
In the meantime, the CD20xCD3 market looks set to become increasingly competitive. Regeneron, Roche, and AbbVie are all running trials designed to expand the label for their drugs in other forms of NHL and earlier lines of therapy.
For its part, Regeneron has studies on the go in mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) and is also testing odronextamab alongside CD22xCD28 bispecific REGN5837 in aggressive B-cell NHL.
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