Regeneron Pharmaceuticals has announced that the European Commission (EC) has granted approval for Ordspono (odronextamab) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL) who have undergone two or more lines of systemic therapy.
This is the first global regulatory approval for Ordspono, a bispecific antibody that targets both lymphoma cells and T cells to facilitate immune-mediated cancer cell destruction.
The EC's decision is based on data from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 clinical trials, which demonstrated strong and sustained response rates in patients with R/R FL or R/R DLBCL:
In patients with R/R FL, the ELM-2 trial (N=128) showed that 80% of patients achieved an objective response, with 73% attaining complete remission. The median duration of response among those in complete remission was 25 months.
For patients with R/R DLBCL who had not received CAR-T therapy, the ELM-2 trial (N=127) showed a 52% objective response rate, with 31% achieving complete remission. The median duration of response for these complete responders was 18 months.
In the ELM-1 trial (N=60) involving patients who had previously progressed after CAR-T therapy, the objective response rate was 48%, with 32% of patients achieving complete remission. Among these responders, the median duration of response was 15 months.
The most frequently reported side effects included cytokine release syndrome (CRS; 54%), neutropenia (41%), fever (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%), and COVID-19 (22%). Serious adverse reactions included CRS (14%), pneumonia (9%), COVID-19 (9%), and fever (6%). Ordspono carries risks of serious or life-threatening infections and CRS.
Understanding Follicular Lymphoma and Diffuse Large B-cell Lymphoma
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the most prevalent subtypes of B-cell non-Hodgkin lymphoma (B-NHL). FL is a slow-progressing yet incurable disease, with most patients experiencing relapse after initial treatment. DLBCL is a more aggressive form, with up to 50% of high-risk patients facing disease progression after first-line therapy. Worldwide, approximately 120,000 cases of FL and 163,000 cases of DLBCL are diagnosed annually, with Europe accounting for around 15,000 FL cases and 31,000 DLBCL cases each year.
Ordspono (odronextamab) Clinical Trial Overview
Ordspono is a CD20xCD3 bispecific antibody that connects CD20 on cancer cells with CD3-expressing T cells, promoting T-cell activation and the targeted killing of cancer cells. Ordspono is approved as a monotherapy for adult patients with R/R FL or R/R DLBCL who have undergone at least two prior lines of systemic therapy.
The ELM-1 trial is an ongoing, open-label, multicenter Phase 1 study assessing the safety and tolerability of odronextamab in patients with CD20-positive B-cell malignancies, including those who have relapsed after CAR-T therapy.
The ELM-2 trial is an ongoing, open-label, multicenter Phase 2 study evaluating odronextamab across five distinct disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma, and other B-NHL subtypes. The trial's primary endpoint is objective response rate (ORR) based on the Lugano Classification, as assessed by an independent review committee (IRC). Secondary endpoints include complete response (CR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR).
Regeneron is also conducting a comprehensive Phase 3 development program, known as OLYMPIA, to evaluate odronextamab in earlier lines of therapy and other B-NHLs. Additionally, the company is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and its PD-1 inhibitor cemiplimab for relapsed/refractory aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. These investigational uses have not yet been evaluated for safety and efficacy by any regulatory authority.