FDA Rejects Roche's Columvi for Earlier DLBCL Treatment, Citing Insufficient U.S. Data

The U.S. Food and Drug Administration (FDA) has declined to approve Roche's Columvi for earlier treatment of diffuse large B-cell lymphoma (DLBCL), dealing a setback to the pharmaceutical giant's expansion plans for the bispecific antibody. The decision highlights growing concerns at the FDA regarding the representation of U.S. patients in global clinical trials.

Columvi's Rejection and the FDA's Concerns

In a complete response letter, the FDA cited insufficient evidence to support the use of Columvi in second-line DLBCL treatment for the U.S. patient population. The rejection was based on data from the Phase III STARGLO study, which combined Columvi with gemcitabine and oxaliplatin in patients with relapsed or refractory DLBCL.

Despite showing a 41% reduction in the risk of death compared to a rituximab-based regimen, the trial's results failed to convince the FDA's Oncologic Drugs Advisory Committee (ODAC). The committee voted 8-1 against Columvi's expansion, primarily due to concerns about the applicability of the efficacy data to U.S. patients. Of the more than 270 participants in STARGLO's intention-to-treat population, only 25 were from North America.

Implications for Global Clinical Trials

The FDA's decision reflects a growing emphasis on ensuring adequate representation of U.S. patients in oncology trials. Dr. Richard Pazdur, the FDA's oncology leader, noted that only about 20% of patients in oncology trials submitted to the agency are from the United States, a figure the FDA would like to see increased.

This issue extends beyond Roche's Columvi. In a separate advisory committee meeting for GSK's antibody-drug conjugate Blenrep, similar concerns were raised about the lack of U.S. patient enrollment. Committee member Daniel Spratt of Western Reserve University pointed out that GSK's "clinical development program enrolled almost no patients in the United States," which he argued "precludes any assessment of the [drug's] benefit-risk profile in the U.S."

Roche's Response and Future Plans

Despite the setback, Columvi remains under accelerated approval for third-line or later DLBCL treatment in the U.S. Roche and its subsidiary Genentech are now in discussions with the FDA to potentially use the ongoing Phase III SKYGLO study as a new postmarketing requirement for Columvi. This study is testing Columvi in combination with Polivy, Rituxan, cyclophosphamide, doxorubicin, and prednisone for the treatment of patients with large B cell lymphoma.

Levi Garraway, M.D., Ph.D., Roche's chief medical officer and head of global product development, expressed disappointment but remained confident in Columvi's value for U.S. patients who have relapsed following initial treatment. He emphasized the company's commitment to exploring Columvi's potential in additional treatment settings, including as frontline therapy.