The Food and Drug Administration (FDA) has accepted the resubmission of the Ordspono (odronextamab) Biologics License Application (BLA) for review in patients with relapsed/refractory follicular lymphoma following two or more lines of systemic therapy, according to a press release from Regeneron Pharmaceuticals, Inc., which was shared on Feb. 26.
The press release went on to note that the target action date for the FDA’s decision to be released is July 30, 2025.
Glossary:
Biologics License Application (BLA): a request to the FDA to market a new biological product in the United States.
Target action date: the specific date by which the FDA aims to make a decision on whether to approve or deny a submitted product.
Complete response letter: a notice issued by the FDA indicating that an application will not be approved in its present form.
Overall response rate: the percentage of patients who have a partial or complete response to a treatment.
Cytokine release syndrome: a systemic inflammatory reaction that occurs when the immune system releases large amounts of cytokines into the bloodstream.
Complete response rate: the percentage of patients who no longer have detectable cancer after treatment.
Progression-free survival: a measure used in clinical trials to evaluate the effectiveness of cancer treatments.
Overall survival: the length of time a patient lives from the date of diagnosis or start of treatment until their death.
The FDA-mandated enrollment target for the phase 3 confirmatory OLYMPIA-1 trial, which was conducted in relapsed/refractory follicular lymphoma, preceded the acceptance of the BLA resubmission. Notably, this was the sole approvability issue cited by the FDA following their complete response letter associated with the initial BLA submission for the agent in the United States. Furthermore, data from the phase 1 and pivotal phase 2 ELM-1 and ELM-2 trials served to support the BLA resubmission from Regeneron Pharmaceuticals to the regulatory agency.
According to the press release, the overall response rate associated with Ordspono treatment was 80% (103 patients), with 74% (95 patients) having achieved a complete response in the phase 1 and pivotal phase 2 ELM-1 and ELM-2 trials. Regarding safety, serious side effects occurred in 67% of patients; those occurring in 10% or more of patients included cytokine release syndrome, COVID-19 and pneumonia.
Follicular lymphoma, the most common subtype of B-cell non-Hodgkin lymphoma, is a slow-growing subtype of this disease; however, it is incurable. Most patients diagnosed with the blood cancer are expected relapse following initial treatment. According to the press release, it is estimated that approximately 122,000 follicular lymphoma cases are diagnosed globally every year with more than 13,600 follicular lymphoma cases anticipated in the United States in 2025 alone.
More Information About The Investigational Agent
Ordspono, a CD20xCD3 bispecific antibody, is designed to engage CD20-expressing cancer cells with CD3-positive T cells, facilitating localized T-cell activation and targeted cancer cell destruction. In the European Union, the agent is approved for the treatment of relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma in patients who have received at least two prior lines of systemic therapy. However, its safety and efficacy have not yet been fully assessed by other regulatory agencies.
The ELM-1 study is an ongoing, open-label, multicenter phase 1 clinical trial evaluating the safety and tolerability of Ordspono in patients with CD20-positive B-cell malignancies who have previously undergone treatment with CD20-targeted antibody therapies. Contrarily, ELM-2 — a multicenter phase 2 study — is currently investigating Ordspono across five distinct disease-specific cohorts, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and other B-cell non-Hodgkin lymphoma subtypes.
The primary end point of the trial is objective response rate, as determined by an independent review committee. Key secondary end points include complete response rate, progression-free survival, overall survival and duration of response.
Ordspono is being evaluated in an extensive clinical development program, both as a monotherapy and in combination with other treatment regimens across various B-cell non-Hodgkin lymphoma subtypes, particularly in earlier lines of therapy, according to the Regeneron Pharmaceuticals news release. In follicular lymphoma, Ordspono is under investigation as a monotherapy in the phase 3 OLYMPIA-1 trial, comparing its efficacy with Rituxan (rituximab) combined with standard-of-care chemotherapy. Additionally, the OLYMPIA-2 trial is assessing Ordspono in combination with chemotherapy in comparison to Rituxan plus standard-of-care chemotherapy.
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