Regeneron's Blood Cancer Drug Odronextamab Faces Partial Clinical Hold by FDA Over CRS Safety Concerns

Compiled by Fan Dongdong

For safety reasons, the U.S. FDA has recently informed Regeneron to suspend multiple clinical trials of its experimental hematologic oncology drug odronextamab (REGN1979).

The FDA has requested Regeneron to further reduce the incidence of Grade 3 cytokine release syndrome (CRS). The trials affected by this suspension include the Phase I monotherapy trial for B-NHL, the interim analysis for chronic lymphocytic leukemia, and monotherapy testing for several B-NHL subtypes.

The FDA’s decision will require Regeneron to pause the recruitment of new patients for the trial, while allowing patients already enrolled to continue receiving the investigational treatment. In addition, the company is required to submit a new protocol amendment to the FDA in accordance with regulatory requirements, with the aim of “resuming patient enrollment in the first quarter of 2021.”

Odronextamab is a CD20 x CD3 bispecific antibody successfully developed by Regeneron using its proprietary Veloci-Bi® bispecific antibody platform. The Veloci-Bi® platform enables the production of full-length bispecific antibodies that closely resemble natural antibodies. Odronextamab exerts its anti-tumor effect by binding to CD20, a protein expressed on B-cell malignancies, and CD3, a receptor on T cells of the immune system, thereby directing T cells to attack tumor cells in patients.

At the 62nd American Society of Hematology (ASH) Annual Meeting held in December, researchers from Regeneron presented trial data on the drug for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). The latest trial data demonstrated that odronextamab exhibited robust single-agent antitumor activity in patients with highly refractory B-NHL. Furthermore, the trial indicated that odronextamab had an acceptable safety and tolerability profile.

Notably, the FDA’s safety concerns regarding this drug are not unique to Regeneron’s odronextamab. Due to their mechanism of action, nearly all CD3-engaging therapies carry a risk of cytokine release syndrome; therefore, apart from temporary protocol modifications, these concerns are not expected to impact the long-term development of Regeneron’s hematologic oncology drug, odronextamab.

Affected by this negative news, Regeneron's stock price fell by 1% in pre-market trading.

References:

1.Regeneron's blood cancer hopeful odronextamab hit with FDA partial hold across several trials

2.Regeneron pause enrollment lymphoma drug