Summary of: Alliance webinar with Dr. Wilson Bryan on cell and gene therapy

Excerpts from Dr. Wilson Bryan OTAT Webinar

Our Alliance webinar this week with Dr. Bryan, Director of the Office of Tissues and Advanced Therapies (OTAT) at the FDA’s Center for Biologics Evaluation and Research, covered current programs, progress in cell and gene therapy, and OTAT’s plans to address its mounting workload. The transcript can be found here.

Anybody interested in cell and gene therapy—patients, sponsors, researchers, providers, and payers—will learn something new and useful from reading the transcript. Here are some excerpts to provide readers with a sense of why it is worth reading the entire transcript:

“With regard to the projection of 800 active cell-based or gene therapy INDs, as of last week, we had 1142 active cell therapy INDs and 1201 active gene therapy INDs. So, that projection of 800….we're well past that in spite of the pandemic. And I expect that these numbers will increase rapidly as we hopefully get out of this pandemic.” (page 3)

“The Center [CBER] has been supportive. OTAT has grown. We are now up to approximately 300 employees. But the number of employees and the growth in OTAT has not kept up with the growth in applications.” (page 4)

“Hiring is a challenge for the FDA. It's challenging partially because our salaries are not competitive with a booming cell and gene therapy industry….So, we keep people at FDA because they believe in our mission of public service and because the work is incredibly interesting. There's so much exciting work going on in cell and gene therapy that it's a lot of fun to work in OTAT. But the salary discrepancy can make recruiting and keeping people a challenge at the FDA.” (page 4)

“Now, we have seven gene therapy approvals right now….The scientific basis for these products is exquisite – and they're lifesaving products. They work. They all were approved based on single-arm studies because they had large effect sizes. And that's one of the things that's been proven in the gene therapy approvals, is that, if there's a large effect size, the clinical trials don't need to be big. And we can do clinical trials in small populations.” (pages 6 and 7)

“Now, the implication, what follows from this, is that the first in-human studies of these products need to be randomized. Folks need to be thinking about whether the very first study could provide the evidence of effectiveness to support a marketing application. We need to stop thinking about doing phase one, then phase two, then phase three studies. In rare disease, there simply aren't enough patients for that paradigm.” (page 7)

“We've got…in the neighborhood of 2500 active INDs. That's just a huge number. If some products that have breakthrough and RMAT designation get extra attention, then that leaves less attention for everybody else. And it comes back to the idea that we can't keep doing business the same as we always have. I think breakthrough and RMAT designations are very valuable because they allow us to focus on products that have provided preliminary evidence that they truly have an effect for patients. But we're going to have to communicate differently for all the other products in order to serve all the patients and bring as many things forward as we can.” (page 9)

“…one of the challenges that we have is receiving applications, IND applications, or meeting requests that really are so grossly deficient that we can't communicate effectively with the stakeholder. And that ends up taking a lot of our time that is not productive and is not really helping the sponsor much either. It's in the best interest of everyone if the sponsor can submit a meeting package, or an IND application, and…[with] the material there that we need to answer the questions and have questions that we can understand….So, we need to do a better job of communicating to our stakeholders so that they can submit INDs and meeting packages that are more effective now.” (pages 11 and 12)

“…we're going to develop new methodologies in nonclinical studies. We're going more in silico models. We're going more to cellular models. And the animal models will continue to be useful to identify doses that hopefully will be, from day one, a benefit.” (page 17)



Editorial Note: The week’s Analysis and Commentary section was written by the Alliance’s Executive Director, Steven Grossman.