▎WuXiEdited by Kant Content Team

Today, Regeneron Pharmaceuticals announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending conditional approval of its investigational bispecific antibody 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 previously received two or more lines of systemic therapy.The European Commission is expected to announce the final review result of the therapy in the coming months.

FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL).Although FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment.DLBCL is an aggressive subtype, with approximately 50% of high-risk patients experiencing disease progression after first-line treatment.It is estimated that there are approximately 120,000 new cases of FL and 163,000 new cases of DLBCL diagnosed globally each year.

The positive opinion of the CHMP is mainly based on the support of the positive results from the Phase 1 clinical trial ELM-1 and the pivotal Phase 2 trial ELM-2, which demonstratedOdronextamab Shows Strong and Durable Response Rates with Acceptable Safety in Adult Patients with R/R FL and R/R DLBCLELM-1 is an ongoing, open-label, multi-center Phase 1 trial designed to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies who were previously treated with CD20-targeted antibodies, including a cohort of patients who experienced disease progression after CAR-T therapy. ELM-2 is an ongoing, open-label, multi-center Phase 2 trial aimed at evaluating the efficacy of odronextamab across five independent disease cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma, and other B-NHL subtypes. The primary endpoint is the objective response rate assessed by an independent review committee according to the Lugano classification, with secondary endpoints including complete response rate, progression-free survival, overall survival, and duration of response.

Regeneron's latest clinical results published at the American Society of Hematology (ASH) Annual Meeting in December last year showed,In the ELM-2 trial, receivingOdronextamab TreatmentThe objective response rate of the FL patient cohort (n=128) was as high as 80%, with a complete response rate of 73%. The median duration of response was 23 months (95% CI: 17-not estimable), and the median duration of complete response reached 24 months (95% CI: 18-not estimable).

▲Odronextamab Demonstrates Positive Efficacy in Treating FL Patients (Image Source: Reference [4])

In the ELM-2 trial, acceptOdronextamab TreatmentCohort of DLBCL Patients (n=127)The objective response rate was 52%, with a complete response rate of 31%.,The median duration of response was 10 months (95% CI:5-18), the median duration of complete response was 18 months (95% CI:10-Not estimable).In addition, an additional analysis of the extended cohort of patients in the Phase 1 trial showed thatThe objective response rate was 48% and the complete response rate was 30% in evaluable patients with DLBCL (n=44). Notably, 73% of these patients were resistant to CAR-T therapy.

▲Odronextamab Demonstrates Positive Efficacy in Treating DLBCL Patients (Image Source: Reference [4])

In the pooled safety evaluation population, the most common serious adverse reactions were cytokine release syndrome (CRS), pneumonia, COVID-19, and fever.

▲Odronextamab Demonstrates Manageable Safety in FL and DLBCL Patients (Image Source: Reference [4])

Odronextamab is an investigational, off-the-shelf, CD20 x CD3-targeted bispecific antibody designed to bridge CD20 on cancer cells and CD3-expressing T cells to promote localized T-cell activation and cancer cell killing.The EMA previously granted odronextamab orphan drug designation for the treatment of FL and DLBCL.

▲Mechanism of Action of Odronextamab (Image Source: Reference [4])

Regeneron will continue to evaluate odronextamab as a monotherapy and combination therapy in earlier treatment lines, particularly in refractory lymphoma.This includes the registrational ELM-1 and ELM-2 trials, the Phase 3 OLYMPIA development program (one of the largest clinical programs evaluating odronextamab in earlier treatment lines and other B-NHL), as well as combination therapy trials without chemotherapy.

▲Development Plan of Odronextamab (Image Source: Reference [4])

In addition, Regeneron is also examining the effects of odronextamab in combination with the costimulatory bispecific antibody REGN5837 (targeting CD22 and CD28) and with the company’s PD-1 inhibitor cemiplimab in relapsed or refractory aggressive B-NHL, as part of the ATHENA-1 and CLIO-1 studies.

References:

[1] Odronextamab Recommended for EU Approval by the CHMP to Treat Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma. Retrieved June 28, 2024 from https://www.globenewswire.com/news-release/2024/06/28/2905764/0/en/Odronextamab-Recommended-for-EU-Approval-by-the-CHMP-to-Treat-Relapsed-Refractory-Follicular-Lymphoma-and-Diffuse-Large-B-cell-Lymphoma.html

[2] LATEST ODRONEXTAMAB DATA IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA SHOWED COMPELLING RESPONSES AND OVERALL MAINTENANCE OF PATIENT-REPORTED OUTCOMES. Retrieved June 28, 2024 from https://investor.regeneron.com/news-releases/news-release-details/latest-odronextamab-data-relapsedrefractory-follicular-lymphoma

[3] UPDATED ODRONEXTAMAB DATA FROM RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA PIVOTAL TRIAL SHOWED DEEP AND DURABLE RESPONSES AND THE POTENTIAL OF CTDNA TO PREDICT LONG-TERM OUTCOMES. Retrieved June 28, 2024 from https://investor.regeneron.com/news-releases/news-release-details/updated-odronextamab-data-relapsedrefractory-diffuse-large-b

[4] American Society of Hematology 2023 I nvestor Event. Retrieved June 28, 2024 from https://investor.regeneron.com/static-files/cb093452-9e37-41b0-9d52-c53b9275e99e

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