The FDA is requiring higher US patient enrollment in global trials to address concerns that results from predominantly non-US populations (e.g., Asia) may not be generalizable. This reflects worries about differences in prior standard-of-care treatments and potential pharmacogenomic variations affecting outcomes.
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A meta-analysis of over 9,500 patients in major prostate cancer trials, including the pivotal VISION and PSMA-4 trials for radioligand therapy, shows significant underrepresentation of Black and Hispanic patients. This creates a critical evidence gap when applying these therapies to diverse real-world populations.
US biotechs increasingly use sites like Australia to accelerate development, as Create Medicines did by moving from concept to clinic in under 12 months. What was once viewed with suspicion is now a key strategy to generate data faster and more cheaply, competing with the speed of China's ecosystem.
Despite strong efficacy data, the drug DV-Toripalimab scored lower than a competitor (2.5 vs 3.0). Experts attribute this confidence gap to its Phase 3 trial being conducted only in China, which raises generalizability concerns and reflects a lack of hands-on experience for Western physicians.
China's ability to accelerate biotech development stems from faster patient recruitment for clinical trials. With a large, treatment-naive patient population willing to participate in studies, early-stage oncology trials can be completed in about half the time it takes in the US. This provides a significant strategic advantage for de-risking assets more quickly and cheaply.
The FDA is predicted to approve new PARP inhibitors from trials like AMPLITUDE only for BRCA-mutated patients, restricting use to where data is strongest. This contrasts with the EMA's potential for broader approvals or denials. This highlights the diverging regulatory philosophies that create different drug access landscapes in the US and Europe.
The STARGLO trial (glofitamab-gemox) showed a strong survival benefit in Asia-Pacific patients but not in the small North American cohort. This geographic discrepancy, with only 9% of patients from the US, was a key reason the FDA did not approve the combination, while European agencies did.
Pirtobrutinib's registrational trials used control arms (ibrutinib, bendamustine-rituximab) that are no longer the standard of care in the US. This strategy reflects the long timeline of trial design and the need to use comparators that are still considered a standard globally, ensuring broader regulatory acceptance and allowing for cross-trial comparisons.
Even with positive results from two registrational Phase 3 trials, experts note a potential regulatory hurdle. The FDA has shown increasing concern over studies with a low proportion of patients from North America, a characteristic of these trials, potentially complicating an otherwise strong case for approval based on clinical merit.
Amidst growing uncertainty at the US FDA, biotech companies are using a specific de-risking strategy: conducting early-stage clinical trials in countries like South Korea and Australia. This global approach is not just about cost but a deliberate move to get fast, reliable early clinical data to offset domestic regulatory instability and gain a strategic advantage.
Xevinapant's Phase III failure, after a promising Phase II trial, was partially attributed to the broader, more heterogeneous patient population. This group experienced greater toxicity than the Phase II cohort, suggesting early-phase safety profiles may not scale, ultimately compromising the efficacy of the entire treatment regimen.