FDA Raises Concerns Over International Clinical Trial Data, Pushes for Increased US Enrollment

The US Food and Drug Administration (FDA) has signaled a potential shift in its approach to evaluating clinical trial data from international studies, particularly those with low US patient representation. This development comes as Roche faces challenges in its bid to expand the use of its diffuse large B-cell lymphoma (DLBCL) drug Columvi, following an FDA advisory committee meeting that highlighted concerns about the applicability of trial results to the US population.

FDA Leadership Calls for Greater US Patient Representation

In an unexpected appearance at the Oncologic Drugs Advisory Committee meeting, FDA Commissioner Martin Makary, M.D., and Richard Pazdur, M.D., the agency's longtime oncology chief, emphasized the importance of US patient enrollment in clinical trials. Makary questioned the agency's ability to make significant decisions based on trials conducted primarily in other countries, particularly China.

Pazdur revealed that only about 20% of participants in oncology trials submitted to the FDA are from the United States. He stated, "We'd like to see robust increased enrollment in the United States," adding that the Oncology Center of Excellence will be closely examining control arms to ensure they represent current US standards of care.

Roche's Columvi Expansion Bid Faces Setback

The FDA's advisory committee voted 8 to 1 against the applicability of Roche's phase 3 Starglo trial results to the US patient population. The trial evaluated Columvi in combination with chemotherapy for second- or later-line treatment of transplant-ineligible DLBCL patients.

Key concerns raised by the committee included:

1. Regional imbalances in overall survival data between Asian and non-Asian countries
2. Low US patient representation (9%) compared to Asian enrollment (48%)
3. Differences in reasons for transplant ineligibility between regions
4. Questions about the relevance of the control arm to current US treatment practices

Despite Roche's efforts to explain the discrepancies, including factors such as increased use of novel therapies in non-Asian countries and differences in patient characteristics, the committee remained unconvinced of the data's applicability to US patients.

Implications for Future Drug Development and Approvals

The FDA's stance on international trial data could have far-reaching implications for pharmaceutical companies developing drugs for the US market. Pazdur emphasized that companies seeking US approval should address US interests and standards of care in their clinical trials.

This development may lead to:

1. Increased pressure on pharmaceutical companies to enroll more US patients in global trials
2. Greater scrutiny of control arms and their relevance to US treatment practices
3. Potential challenges for drugs developed primarily with data from non-US populations
4. A renewed focus on ensuring clinical trial designs reflect the diversity and treatment landscape of the US patient population

As the pharmaceutical industry adapts to these evolving regulatory expectations, companies may need to reassess their clinical trial strategies to ensure they meet the FDA's emerging criteria for US market approvals.