FDA Rejects Roche's Columvi for Earlier DLBCL Treatment, Citing Insufficient US Data

The U.S. Food and Drug Administration (FDA) has declined to approve Roche's Columvi (glofitamab) in combination with GemOx chemotherapy for the treatment of second-line diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem cell transplant. This decision, announced by Roche and its subsidiary Genentech on July 18, 2025, marks a significant setback for the company's efforts to expand Columvi's use in earlier lines of therapy.

FDA Concerns Over US Patient Representation

The FDA's complete response letter cited concerns that the phase 3 Starglo trial data did not provide sufficient evidence to support the proposed indication in a U.S. population. This decision aligns with the recent FDA advisory committee meeting, where external experts voted 8 to 1 against the applicability of Starglo results to U.S. patients.

The Starglo trial, which showed a 41% reduction in the risk of death for the Columvi-GemOx regimen compared to Rituxan-GemOx in the overall population, faced scrutiny due to regional disparities in outcomes. FDA subgroup analysis revealed a 6% higher risk of death for the Columvi regimen in non-Asian countries, raising questions about its efficacy in Western populations.

Notably, only 9% of Starglo trial participants were from the United States, a factor that drew significant attention from regulators. Dr. Richard Pazdur, the FDA's oncology leader, emphasized the need for increased U.S. enrollment in oncology trials, stating, "Unfortunately, if you take a look at all the oncology trials that come to us, only about 20% of the population is derived from the United States. We'd like to see robust increased enrollment in the United States."

Implications and Future Directions

Despite this setback, Columvi retains its accelerated approval in the third-line DLBCL setting. Roche is now in discussions with the FDA to potentially use the phase 3 Skyglo study as a confirmatory trial for full approval. Skyglo is evaluating Columvi in combination with Roche's Polivy-R-CHP regimen in previously untreated CD20-positive large B-cell lymphoma patients.

Dr. Levi Garraway, Roche's chief medical officer and head of global product development, expressed disappointment but remained optimistic about Columvi's potential. "While we are disappointed with this outcome, we remain confident in the data supporting the value of Columvi for U.S. patients who have relapsed following initial treatment, and its key role as monotherapy in the third-line setting," he stated. "We are committed to bringing Columvi to more people living with lymphoma and are actively exploring its potential in additional treatment settings, including as frontline therapy."

This rejection highlights a growing trend in FDA scrutiny of oncology trials, emphasizing the importance of robust U.S. patient representation in clinical studies. The decision also underscores the challenges pharmaceutical companies face in navigating regulatory requirements across different regions, as evidenced by the contrasting approval Roche received for the same indication from European regulators.