Accelerated Approval, Sponsor Alliances, Master Protocols: Three Ways To Increase Odds Of Regulatory Approval
By Life Science Connect Editorial Staff
For U.S. pharma companies aiming to make their therapeutic commercially available worldwide, the goal is securing approval from the FDA and global regulators in any ex-U.S. locations where they would like the product to be accessible. If you are opting to qualify a global development program for an accelerated regulatory pathway with the FDA, you will need to balance FDA requirements with those associated with other critical markets, including Europe and Japan. To ensure regulatory buy-in, build out a thoughtful strategy from the early phases of research and development. As you consider how to satisfy a range of regulatory expectations, compare innovative techniques, including collaboration with other sponsors on a master protocol.
Is Accelerated Approval Right For Your Therapy?
If a pharma company is debating whether to seek Accelerated Approval from the FDA, there are a few angles to be cognizant of. Accelerated Approval is granted to “allow earlier approval of drugs that treat serious conditions, and to fill an unmet medical need based on a surrogate endpoint.”1 Surrogate endpoints are indicators that are purported to predict clinical benefit while not being actual measures of clinical benefit. In many cases, their usage shortens a drug’s timeline to FDA approval.
If a drug company opts to seek Accelerated Approval, they will eventually need to demonstrate actual evidence of the clinical benefit, i.e., what was not delivered in their initial dossier. If your team has strong confidence in their ability to procure those missing components, Accelerated Approval could be an effective strategy. However, if there is uncertainty as to whether it can be achieved, this would be a very risky approach. At Exscientia, an AI drug discovery company, their team assesses confidence in Accelerated Approval success via AI technology and data generation. Their approach is to craft development strategies based on the operating data gained via simulations. If not already implemented within your program, AI and modeling technologies could help you gain a more robust understanding of whether Accelerated Approval or another approach is best suited for your protocol.
Are Sponsor Alliances The Way Forward?
Historically, drug developers have considered their clinical trials in isolation, apart from other drugs entering the pipeline. However, for the patient weighing lifesaving therapies, the sponsor of said therapies is of little significance. Similarly, health authority reviewers are looking at the totality of different programs coming across their desks. In this way, only sponsors view their programs as separate from the larger landscape they are a part of.
Though the prospect of integrating knowledge across drug developers may sound far-fetched, examine the success of the I-SPY 2 trial. I-SPY 2 is an ongoing platform trial for neoadjuvant treatment of locally advanced breast cancer, the first of its kind. By leveraging a master protocol, I-SPY 2 assesses the clinical impact of multiple therapies within the same study. New drug candidates can enter and leave the study without the protocol being resubmitted for regulatory review.
According to former FDA Commissioner Janet Woodcock, “I-SPY 2 is the longest running of these adaptive platform trials and its many successes come from the design, collaboration under a master protocol, and a number of other unique features that create a sustainable learning system. Development of new therapies will become more patient-centric and efficient as companies and organizations adopt these trials.”2 As sponsors work to ensure FDA and ex-U.S. approval, further exploring how to design integrated master protocols across multiple sponsors could yield major advantages.
Does The Master Protocol Suit Your Needs?
Over the years, many pharma companies have experimented with the master protocol to determine whether it is realistic for their therapies, and some organizations find greater success when pooling their expertise and experience. For many sponsors, this approach may evoke concerns about intellectual property rights. However, with thoughtful parameter setting, it can yield more effective development approaches that increase knowledge for developers and deliver drugs to patients more efficiently. Ultimately, the choice depends on your therapy, your intended pathway to FDA approval, and your global commercialization goals.
For more information about designing clinical trial protocols, watch the recent Clinical Leader Live event Trial Protocol Design Do’s and Don’ts.
References:
- Center for Drug Evaluation and Research. Accelerated approvals. U.S. Food and Drug Administration. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program
- Quantum Leap Healthcare Collaborative. I-Spy 2, an innovative clinical trial model that is revolutionizing the treatment of early stage, high-risk breast cancer. The I-Spy Trials. https://www.ispytrials.org/newsitems/2018-press-event