Odronextamab got a conditional marketing authorisation valid across the European Union on 22 August 2024. Sold as Ordspono, it is meant for adults whose follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) has returned or stopped responding after at least two earlier systemic therapies. Regeneron Pharmaceuticals, the developer, announced the European Commission’s decision on August 26, 2024.
CancerNetwork said it is the first approval anywhere for odronextamab in this use. The European Medicines Agency’s human medicines committee had backed it in June 2024.
How the drug works
Odronextamab is a bispecific antibody. It latches onto two targets at once: CD20, a protein on the surface of B cells, including cancerous ones, and CD3, a protein on T cells, which belong to the immune system. By pulling the two cell types together, the drug activates the T cells, and they kill the cancer cells, according to the EMA.
It is given as an infusion into a vein. Treatment begins with four 21-day cycles. In the first, infusions come on days 1, 2, 8, 9, 15 and 16 at rising doses. In cycles 2 to 4 they come on days 1, 8 and 15. After that the interval is every 2 or 4 weeks, depending on response, until the disease worsens or side effects become unacceptable. Patients receive premedication to reduce the risk of cytokine release syndrome.
What the trials showed
The approval draws on the phase 2 ELM-2 trial and the phase 1 ELM-1 trial. In follicular lymphoma, an independent review committee found an objective response rate of 80% among 128 evaluable patients, with complete responses in 73%. Among patients who had a complete response, the median duration of response was 25 months.
In 127 DLBCL patients with no prior CAR T-cell therapy, the response rate was 52% and the complete response rate 31%. Those with a complete response had a median duration of response of 18 months. Among 60 DLBCL patients whose disease progressed after CAR T therapy, the response rate was 48%, and 32% had a complete response.
The EMA noted that the study did not compare odronextamab with any other treatment.
“In clinical trials, [odronextamab] demonstrated remarkable complete response [CR] rates in follicular lymphoma,” said Stefano Luminari, a professor of oncology at the University of Modena and Reggio Emilia, in Regeneron’s press release. He added that physicians “will have an off-the-shelf option that can be administered out-patient.”
Side effects
Pooled safety data from the two trials listed cytokine release syndrome in 54% of patients, neutropenia in 41%, pyrexia in 39%, anemia in 38%, thrombocytopenia in 27% and diarrhea in 24%. Serious events included cytokine release syndrome in 14%, and pneumonia and COVID-19 in 9% each. Patients will carry an alert card describing the risk of cytokine release syndrome and neurological toxicity, including ICANS.
Conditions attached
The authorisation is conditional because the drug meets an unmet medical need and rests on less complete data than usual. Regeneron must submit data comparing it with other therapies, and the EMA will review new information every year.
George D. Yancopoulos, Regeneron’s president and chief scientific officer, said the approval is the first from the company’s bispecific antibody platform. Regeneron is running the OLYMPIA program of phase 3 trials, testing odronextamab as a monotherapy and in combinations in earlier lines of therapy.
Sources
- Odronextamab Earns European Approval in R/R Follicular Lymphoma, DLBCL | CancerNetwork
- Ordspono | European Medicines Agency (EMA)
