In recent years, development programs for cell and gene therapies (CGT) have been on the rise. CGT have the promise to do more than manage symptoms; they have the potential to reverse and even cure disease. As we would all like to help patients sooner rather than later, the following question arises: Are there ways to accelerate CGT development? To find out, I attended a webinar presented by my colleagues, Drs. Emily Woodward and Maximilian Vargas, entitled “Commercial and Regulatory Success in Accelerated Gene Therapy Development.” They highlighted 3 major ways to accelerate and streamline the development of CGT:
1. Early and frequent interactions with the health authority
Although the webinar focused on interactions with the United States Food and Drug Administration (FDA), the idea is applicable to regulatory agencies worldwide: early and frequent interactions with health authorities will help ensure alignment and streamline your CTG development program. As an example, according to the FDA the average development time was 12.8 years for drugs without a pre-Investigational New Drug (IND) meeting compared to 7.1 years for drugs with a pre-IND meeting. But don’t wait to communicate with the FDA until the pre-IND stage! For innovative investigational products such as CGTs, there is an option for an informal, non-binding, one-time consultation with Center for Biologics Evaluation and Research (CBER) in the form of the Initial Targeted Engagement for Regulatory Advice on CBER producTs or INTERACT meeting. This consultation meeting focuses on nonclinical (product characterization and early proof-of-concept) studies and CMC-related-challenges. Note that INTERACT and pre-IND meetings require a selected drug product. If you have a novel technological platform but no selected drug product, consultation on non-product specific questions or candidate product selection can be requested through a CBER Advanced Technologies Team or CATT meeting.
Does that mean that options to expedite CTG development end with a pre-IND meeting? No, it does not. There are several mechanisms for expedited development and approval: fast-track designation, breakthrough designation, regenerative medicine advanced therapy designation, orphan drug designation, accelerated approval, and priority review. A benefit of the designations is increased interactions with the FDA. Also, the 6 mechanisms are not mutually exclusive, so sponsors are encouraged to pursue any and all relevant mechanisms.
2. Early interactions with end users
When we think about drug development, we often immediately think about guidance documents written by and interactions with health authorities. But drug development is like raising a child: It takes a village! In the webinar, other valuable sources of information were pointed out: patients and their caregivers, physicians, and payers. Perhaps these should be considered the 3 P’s of drug development!
Input from the 3 P’s should be gathered early in development, preferably as early as during your target product profile (TPP) development prior to evaluation of the CTG in the clinic. As the presenters said: “It is never too early!” Why should you seek input from the 3 P’s? Getting input from payers may guide you on how your inclusion and exclusion criteria affect the reimbursable population. Input from patients and physicians may help you discover what they would consider to be clinically relevant surrogate or intermediate endpoints for your proposed disease indication. Appropriate surrogate or intermediate endpoints can shorten time in development as they allow for early trial readouts and may make your CGT eligible for accelerated approval.
3. Do not discard the value of real-world evidence
Real-world evidence (RWE) derived from real-world data (RWD) can strengthen your data package for your CGT regulatory submission. An example is natural history data about disease pathogenesis, which proved invaluable for the development and approval of a CGT for spinal muscular atrophy. RWD can come from a variety of sources, including case-controlled studies, observational studies, and disease registries, but may not always be readily available. Identification of valuable RWD early on and prospective planning of (longitudinal) RWD collection can set you apart from your competitors.
By seeking early input from regulatory and end users and incorporating insights gained from RWE, you are more likely to attain regulatory and commercial success for a CGT product that will truly benefit patients. To find out more, click the following link to watch the webinar: