CBER's Dr. Peter Marks, ARM's Mike Lehmicke On Genome Editing Technologies
By Erin Harris, Editor-In-Chief, Cell & Gene
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Just recently, the FDA’s Center for Biologics Evaluation and Research (CBER)’s Director, Dr. Peter Marks, joined me as my guest on Cell & Gene: The Podcast. To date, Dr. Marks has been my only repeat guest; the original episode aired earlier this year. During that episode, he and I discussed PDUFA VII’s impact on CGT biotechs as well as innovations in clinical development. Dr. Marks also provided recommendations to companies in their engagement with the FDA that could make manufacturing more streamlined and cost effective.
This time around, Dr. Marks and I discussed prime editing, base editing, and their impact on unmet medical need. He details the differences between the two forms of genome editing technologies. We discuss whether the regulatory landscape has embraced prime and base editing as well as what the FDA has to say about some of the recent clinical holds in the CGT space.
Later in the episode, I asked Dr. Marks whether the FDA is prepared to approve a base editing therapy that alters the germ line and becomes inheritable. Dr. Marks explained that an appropriations rider prevents FDA by law from accepting a drug application that deliberately targets the correction of an inheritable condition. “If that changes at some point, we’ll be ready for it,” says Marks. He also stated that CBER can “tolerate some uncertainty” about base editing or prime editing therapies that don’t deliberately target germ cells, but nevertheless “could possibly have an effect on the germ line as an incidental effect.” Women of child-bearing potential, for example, would not necessarily need to be excluded from clinical trials testing such a product. Marks stated the agency will want to minimize the chance of an inheritable modification to the greatest extent possible, but at the end of the day, “I don’t think it will be a deal-breaker” for approval.
If you’re interested in learning more about base editing and prime editing, here’s another episode of Cell & Gene: The Podcast you’ll want to check out. In it, I talked to Prime Medicine’s Dr. Andrew Anzalone about why prime editing is a major technological advancement in gene editing. Dr. Anzalone also explains why prime editing has a broad applicability for different tissue and cell types that can be used in different therapeutic applications.
To get his take on the topic of genome editing, I caught up with Mike Lehmicke, Vice President, Science and Industry Affairs, Alliance for Regenerative Medicine (ARM). Lehmicke and I discussed whether we will see CRISPR therapies approved to be used in the U.S., the state of the current clinical pipeline, as well as advanced techniques, such as prime editing. Here’s what Lehmicke had to say, in part, about prime editing:
Prime editing is currently being explored in early clinical research. Like base editing, prime editing also ‘nicks’ the DNA strand. What differentiates it is that it can address all 12 types of base pair modifications of the DNA, and the technique can potentially correct up to 89% of known genetic variants associated with human disease. While there is still much to be understood about the potential of prime editing, early studies have shown that it can be used to correct mutations that cause different forms of liver disease. Researchers are also exploring how it can be applied to other diseases like spinal muscular atrophy, cystic fibrosis, cataract disorder, and Wilson disease. Epigenetic editing, on the other hand, is being investigated as a way to control gene expression. This technique has been explored over the past decades and is starting to reemerge as a viable practice thanks to recent technological advancements.
Read my full-length discussion with Lehmicke here.
Genome editing technologies are evolving rapidly. I’d love to hear from you how your company is using next-generation genome technologies to advance therapeutic applications.