In a significant setback for Roche's subsidiary Genentech, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted overwhelmingly against expanding the use of its bispecific antibody Columvi. The committee voted 8-1 on Tuesday against approving the combination of Columvi with gemcitabine and oxaliplatin for transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Concerns Over Study Population Representation
The primary concern raised by the advisory committee centered on the applicability of Genentech's Phase III STARGLO study data to the broader U.S. population. Committee members highlighted that Asian patients comprised approximately half of the study's intention-to-treat population, while only 25 patients were enrolled from North America.
Ravi Madan, head of Prostate Cancer Clinical Research at the National Cancer Institute and a committee member who voted against the expansion, explained: "While therapeutic development in oncology is an increasingly global operation, drug sponsors need to make deliberate decisions to ensure their data does apply to the U.S. population."
The FDA similarly flagged this issue in its presentation, noting several factors that could affect the applicability of foreign data to U.S. patients, including differences in diet, environmental exposures, and genetic polymorphisms between these patient populations.
Current Approval Status and Proposed Expansion
Columvi is a bispecific antibody designed to target both CD20 and CD3 proteins. The biologic initially received FDA approval in June 2023 for patients with R/R DLBCL who had undergone at least two prior lines of systemic therapy.
Genentech was seeking to expand its use to R/R DLBCL patients who cannot undergo autologous stem cell transplantation. The company emphasized in a Tuesday news release that this patient population has an "urgent need for effective, immediately available therapies."
Broader Context in Oncology Treatment
The negative vote comes at a time when bispecific antibodies are gaining traction in hematologic malignancies. For R/R DLBCL patients who are ineligible for transplantation, treatment options remain limited, highlighting the significant unmet need that Genentech was attempting to address.
Other ODAC Decisions
In contrast to the Columvi decision, during the same advisory committee meeting, ODAC gave its backing to Johnson & Johnson's Darzalex Faspro. This anti-CD38 antibody, already approved for multiple myeloma indications, received a positive recommendation for expansion to adult patients with high-risk smoldering multiple myeloma.
Implications for Genentech and Patients
The negative vote does not necessarily mean the FDA will reject Genentech's supplemental biologics license application, as the agency is not bound by the committee's recommendation. However, the FDA typically follows the advice of its advisory committees.
For patients with transplant-ineligible R/R DLBCL, the committee's decision potentially delays access to what could have been a new treatment option. Genentech will likely need to provide additional data with better representation of U.S. patients to support future applications for this indication.
The company has not yet announced whether it plans to conduct additional studies with greater U.S. patient representation or pursue alternative strategies to address the committee's concerns.
