US biotech companies are increasingly looking to conduct early-stage clinical trials outside the United States as confidence in the Food and Drug Administration (FDA) wavers following recent leadership changes and staff departures. This shift represents a potential reshaping of traditional drug development pathways that have historically prioritized the US market.
The resignation of top FDA official Peter Marks last month triggered immediate concerns among biotech executives. For smaller companies like Siren Biotechnology, the departure of key regulatory figures has prompted a strategic reevaluation of where to conduct initial clinical testing.
Regulatory Uncertainty Drives Strategic Shifts
Several biotech executives, investors, and consultants report that companies are now considering launching trials in markets such as the European Union and Australia, while engaging with those regions' regulators earlier in the drug development process.
"We know that across our companies, the discussions include whether to go ex-U.S. because of recent FDA uncertainty," said Peter Kolchinsky, managing partner at RA Capital, which manages approximately $9 billion in assets focused on biotech investments.
This sentiment is echoed by Sabrina Martucci Johnson, CEO of Dare Bioscience, a women's health biotech company valued at $25 million. "What's happening has forced all of us to discuss other approaches," Johnson stated. "We are definitely looking at Europe first for certain products where the need is great and the U.S. regulatory path has become more uncertain or slower."
Financial and Operational Implications
The strategic pivot comes with significant financial implications. One biotech CEO, speaking anonymously, revealed plans to seek European Medicines Agency (EMA) approval for early-stage oncology trials across three European countries—in addition to an ongoing US trial. This expanded European strategy will cost approximately $1 million in additional filings, consultants, and research organization support, plus several million more to run the trials.
"We cannot just hope that things will turn around and that the cuts at the FDA will not have any impact on our business," the executive explained. "The irony of this is it goes against the grain of 'America First', because we are offshoring away from the U.S. over to Europe."
Another US biotech opted to run two early-stage trials in Australia rather than the US, citing FDA staffing cuts and uncertainty as primary drivers of this decision, despite Australia already being a popular choice due to 30-40% lower costs.
Staffing Concerns and Review Timelines
Staff departures at the FDA are creating tangible concerns about review timelines. One biotech CEO reported that at least two members of an eight-person FDA team reviewing their early-stage trial for an mRNA rare disease therapy have left the agency. For small biotechs operating with limited funding runways, even minor delays in regulatory steps can have existential implications.
"Europe has been perceived as a little slower, but it has benefited—and is benefiting now—from being stable," noted Owen Smith, a partner at 4BIO Capital, a London-based venture capital firm investing in early-stage biotech companies.
Divergent Impacts Based on Company Size
While smaller biotechs express growing concern, larger pharmaceutical companies report minimal disruption. During recent earnings calls, executives from GSK, Merck & Co, and Sanofi indicated they had not experienced any changes in their interactions with the FDA.
This divergence highlights the particular vulnerability of smaller biotech companies to regulatory uncertainty. For these firms, delays in the development timeline can significantly impact investor confidence and funding prospects in an already challenging capital environment.
Long-term Industry Implications
Industry experts warn that a sustained loss of confidence in the FDA could fundamentally reshape drug development, potentially reducing US leadership in biomedical innovation and increasing costs across the struggling biotech sector.
Matthew Weinberg of ProPharma Group, a consulting firm, noted an increase in inquiries from biotech companies about preparing filings with the EMA and setting up clinical trials outside the US—a shift he attributes directly to growing concerns about FDA stability.
Despite these strategic adjustments, most companies emphasize they still intend to run late-stage trials in the US and ultimately seek FDA approval to access the approximately $635 billion US pharmaceutical market. The current shift primarily affects early-stage development, but signals a potentially significant change in how biotech companies approach the regulatory pathway.
The European Medicines Agency has not yet reported an increase in scientific advice requests or clinical trial applications, noting it would be premature for such shifts to be reflected in formal submissions. However, the strategic discussions happening across the biotech industry suggest that regulatory stability may become an increasingly important factor in global drug development decisions.
