In recent years, we have observed a significant increase in use of expedited programs offered by the U.S. Federal Drug Administration (FDA). These programs are specifically intended to facilitate the development and review of novel drugs that address unmet medical needs in treating serious or life-threatening conditions. In 2020, more than half of the approved new drugs or original biologic license applications (BLAs) in oncology were designated under an accelerated approval pathway, with 11 accelerated approvals of the total 19 approvals.
Currently, there are five expedited programs, which are relevant at different points in the drug development journey. For sponsors aiming to accelerate the availability of potentially life-saving therapies to patients in need, it’s essential to understand these programs and their distinct and overlapping criteria and features.
Expedited Programs Applicable to Both Drug and Biologics in Oncology
In oncology, four programs are applicable to both drugs and biologics. They share the prerequisite that the investigational medical product (IMP) is intended to treat a serious condition. But each has different programmatic requirements, as summarized below.
- Fast-track designation. FTD requires that nonclinical or clinical data demonstrate the potential to address an unmet medical need in patients with a serious condition. Advantages of FTD include actions to expedite development and eligibility for priority and rolling review if relevant criteria are met.
- Breakthrough therapy designation. BTD requires that preliminary clinical evidence indicates that the product may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. Advantages of BTD include all the elements of FTD, plus intensive guidance on efficient drug development and organizational commitment involving senior managers.
- Priority review designation requires that an IMP, if approved, would provide a significant improvement in safety or effectiveness over treatments currently available. Under priority review, the FDA will take action on an application within six months (compared to 10 months under traditional review).
- Accelerated approval. AA requires that a drug or biologic has an effect on surrogate or intermediate endpoints that will be reasonably likely to predict clinical benefit, taking into consideration the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatment. For drugs or biologics that have been granted accelerated approval, post-marketing confirmatory trials are required to verify and describe the clinical benefit.
Expedited Program Applicable Only to Biologics in Oncology
In oncology, while the programs described above are applicable to both drugs and biologics, the regenerative medicine advanced therapy (RMAT) program is restricted to biologics of cell and gene therapy (CGT). These therapies are regulated by the Center for Biologics Evaluation and Research (CBER) within the FDA.
The RMAT program is intended to facilitate development and review of regenerative medicine therapies, which involve using stem cells, engineered biomaterials, gene editing, and other technologies to repair or replace damaged cells, tissues, or organs.
In general, regenerative medicine therapies include cell therapies, therapeutic tissue engineering products, and human cell and tissue products. Examples of regenerative medicine therapies for cancer treatment include, for example, human gene therapies and genetically modified cells. In addition, combination products (such as biologic-device, biologic-drug, or biologic-device-drug) can be eligible for RMAT designation, when the primary mode of action of the combination product is conveyed by the biological product constituent part.
Under the 21st Century Cures Act, a regenerative medicine therapy can be designated as a regenerative advanced therapy when:
- It meets the definition of regenerative medicine therapy;
- It is intended to treat, modify, reverse, or cure a serious condition; and
- Preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such condition.
Besides encompassing all BTD features, the benefits of RMAT designation also include a statute addressing potential ways to support accelerated approval and satisfying post-approval requirements. In addition, sponsors of RMAT products that receive accelerated approval may be able to fulfill their post-approval requirements with clinical evidence obtained from sources other than traditional confirmatory trials. This could include:
- Submission of clinical evidence, clinical studies, patient registries, or other sources of real-world evidence, such as electronic health records;
- Collection of larger confirmatory data sets as agreed upon during product development; or
- Post-approval monitoring of all patients treated with such therapy prior to its approval.
To facilitate the development of regenerative medicine therapies, we recommend that sponsors consider flexibility in clinical trial design including adaptive designs, enrichment strategies, or novel endpoints.
The expedited programs are intended to help ensure that therapies for serious conditions are approved and available to patients as soon as the evidence demonstrates that the benefits of the therapies justify their risks. To facilitate the clinical development of promising products via an expedited program, we strongly recommend that sponsors engage in discussion with the FDA early in the product development process.
Our team of experts here at CATO SMS have long experience and in-depth expertise in every aspect of clinical and regulatory strategy. We can support you with early engagement with the FDA, and with responding promptly to inquiries conveyed via written correspondence, during formal meetings, and other interactions – crucial for taking best advantage of expedited programs.