“It would not be surprising to not see new FDA guidance documents issued for some period of time,” said David Larwood, CEO of Valley Fever Solutions, about the potential impact of the US Food and Drug Administration’s (FDA) staff cuts and recent administrative realignment and synchronisation.
An FDA guidance is a critical document that conveys regulatory expectations on trial design, endpoints, and product development pathways. Larwood highlighted how the most recent finalised guidance that focused on traditional and surrogate clinical trial endpoints, which was released in 2018, remains important for how sponsors structure trials, especially in cancer drug development. Although several draft guidance documents have been issued since, including those in late 2023 and March 2024, the 2018 guidance continues to influence how sponsors structure trials, especially in cancer drug development, Larwood noted.
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Larwood was speaking at the 15th Annual Clinical Trial in Oncology West Coast (CTO) conference, which saw clinicians, clinical trial and technology experts in the field of oncology gather to discuss the latest issues and challenges in the field.
At the beginning of his talk, Larwood commented on the uncertainty surrounding potential regulatory changes, especially with new leadership. He reiterated FDA Commissioner Marty Makary’s words when he announced the appointment of Vinay Prasad as head of the Center for Biologics Evaluation and Research (CBER), saying Prasad brings “scientific rigor, independence, and transparency” to the role. Nonetheless, the new leadership brings uncertainty. On the one hand, there is hope for data-driven policies, but there are also concerns due to Prasad’s past critiques of Covid-19 measures and FDA policies, he said.
Expedited approval offers advantages to patients and investors
Larwood highlighted the impact of accelerated drug approvals, particularly in the field of oncology, due to the high financial impact for investors and transformative potential for patients. An asset’s faster approval results in benefits sooner for patients plus potential higher revenues, motivating investors and company stakeholders, he said, noting that confirmatory trials are an important path for some accelerated approvals and solid data is always important.
Different accelerated schemes and their unique requirements
Cancer remains a leading cause of death globally and in the US, accounting for about 17% of US deaths, which underlines the urgency for expedited approval of effective treatments, Larwood highlighted.
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By GlobalDataThe FDA offers expedited review pathways, however, even after approval, post-marketing requirements and confirmatory studies may be needed to evaluate the drug’s long-term benefits and safety.
For a drug program to be eligible for schemes such as Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review, the clinical data package can be based on non-traditional or surrogate endpoints such as tumour shrinkage or biomarker changes. Larwood said that, according to guidelines, the FDA prefers randomised controlled trials (RCTs) and well-structured data, but is still open to novel endpoints. For Accelerated Approval, solid data and confirmatory trials are essential, and if follow-up data does not confirm an asset’s clinical benefit, then approval can be withdrawn, Larwood emphasised.
A Fast Track designation speeds up development and review for drugs showing potential to address serious conditions, providing benefits like more frequent FDA interaction and rolling New Drug Application (NDA) submissions. A Breakthrough Therapy designation applies to drugs showing substantial improvement over existing treatments, particularly with meaningful clinical endpoints such as reduced mortality or improved symptoms. Breakthrough designation includes all Fast Track benefits in addition to dedicated guidance from senior FDA leadership. The Accelerated Approval pathway allows earlier approval based on surrogate endpoints likely to predict clinical benefit, while the Priority Review programme commits the FDA to act within a shortened timeline.
Fast Track or Breakthrough therapy designations are making a substantial difference in the oncology space. In indications such as lung cancer, death rates have dropped, likely due to the availability of effective therapies.
The Regenerative Medicine Advanced Therapy Designation (RMAT) designation, specifically for cell and tissue-based therapies, is key in some newer oncology therapies. Although it shares many benefits with other expedited pathways, Larwood pointed out that RMAT also allows the use of real-world evidence, adding flexibility and relevance to regulatory submissions. While these developing pathways are promising, high costs remain a major concern and may pose access barriers, Larwood said.
