The first white paper, “Modernizing Expedited Development Programs” focused on expediting the development of drugs at the pre-clinical and clinical stages. On Day 2 of the 2020 Friends of Cancer Research (Friends) Annual Meeting, panelists will examine the second whitepaper, “Optimizing the Use of Accelerated Approval.” This white paper examines opportunities to optimize accelerated approval to expedite the review process and deliver treatments to patient faster.
The Accelerated Approval (AA) program is an important regulatory mechanism that was developed in response to the HIV/AIDS epidemic enabling the FDA to permit earlier approval of drugs treating serious and life-threatening illnesses. AA utilizes surrogate or intermediate clinical endpoints reasonably likely to predict clinical benefit, in lieu of traditional, direct clinical endpoints, such as overall survival (OS), to facilitate earlier patient access coupled with additional evidence generated from post-approval confirmatory commitments. The white paper outlines why AA is important for patients, identifies challenges, and suggests improvement for AA application in oncology.
“The Accelerated Approval pathway is a crucial tool for lethal diseases such as cancer to get treatments to patients earlier based on earlier endpoints leading to preliminary favorable benefit-risk determinations. This white paper lays out some innovative proposals on how to shore up this pathway for continued benefit to patients suffering from cancer for the future” – Gideon Blumenthal, Merck
AA provides earlier access to novel therapies compared to the regular FDA approval pathway. Therapies receiving AA were made available a median of 3.4 years earlier compared to what would be achievable if confirmation of OS was required at the time of approval. As more advanced treatments are developed that markedly extend survival rates, quantifying OS will not only become more difficult within the context of a clinical trial, but also raise questions of equipoise to require OS for drugs to treat patients with life-threatening diseases. Drug development through the AA pathway could be enhanced if shifted toward a benefit-risk assessment. A preliminary benefit-risk assessment that includes consideration of outcomes of a surrogate endpoint, may reflect a more holistic consideration of factors that are important to patients in approval determination.
The white paper outlines several recommendations to improve on AA within the framework of a benefit-risk assessment in regulatory determinations. A few of these recommendations for consideration in pre-approval drug development include a pathway to support evidence generation and reporting to encourage development of new and further validation of current surrogate endpoints in the pre-approval setting, a requirement for enrollment to confirmatory trials at the time of a new drug application, and greater use of historical controls in clinical trials to support evidence generation while maintaining equipoise. The white paper recommends several post-approval improvements to AA including seeking public input on AA decisions where a confirmatory trial fails, strengthening FDA authority to require additional confirmatory studies when appropriate, and broadening use of real-world evidence to study an AA therapy.
The AA pathway is an important mechanism to promote development and access to life-saving therapies. As drug development and technologies advance and begin to extend overall survival for cancer patients by years and decades beyond current standard of care, the AA program will need to evolve in anticipation of future medical advancements and patient need. This white paper outlines specific recommendations to improve the AA framework to continue to facilitate patient access to potentially life-saving therapies.
To register for Day 2 of the Friends Annual Meeting, click here.
