By 2025, between 10 and 20 new gene therapies could win approval annually by the US Food and Drug Administration (FDA), most of them delivered via adeno-associated virus (AAV). 

Yet Duchenne muscular dystrophy (DMD) presents some unique challenges for AAV-delivered gene therapy — namely because the dystrophin gene, which is missing in DMD, is one of the largest in the human genome, with more than 3 times the AAV’s packaging capacity. 

Those challenges were the focus of an online session hosted by the nonprofit group CureDuchenne as part of its 2021 Futures National Conference. The 2-hour panel included 9 presentations by officials representing pharmaceutical companies including Pfizer, Solid Biosciences, Vertex Pharmaceutical, and Sarepta Therapeutics.

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“What may come as a surprise to a lot of families is that gene therapy isn’t new. The roots of gene therapy can be traced back more than 30 years, and the first gene therapy products were approved only 4 years ago,” said Michael Kelly, PhD, CureDuchenne’s chief scientific advisor. The earliest were CAR T cell-based therapies for cancer and Luxturna to treat a rare form of congenital blindness—both approved by the FDA in 2017.

In 2019, the FDA approved Zolgensma, a one-time intravenous gene therapy costing $2.125 million, to treat spinal muscular atrophy. And today, there are hundreds of gene therapy clinical trials in progress worldwide, Dr. Kelly said.

In order to make gene therapy work for DMD, though, genes must be shortened so that they are amenable to AAV-mediated delivery. As such, multiple individual gene constructs are now in clinical development, including Pfizer’s PF-06939926, Sarepta’s SRP-9001, and Solid’s SGT-001.

Yet, as Dr. Kelly noted, some of the biggest hurdles in gene therapy when it comes to Duchenne include the durability of response as DMD boys grow, the high doses needed to target muscle tissue, and finally, pre-existing immunity to AAV, which would render a significant portion of patients ineligible for gene therapy treatment.

“AAV-delivered gene therapy presents novel challenges,” he said. “Understanding these will be critical to recognizing the full scope of this technology to effectively treat monogenic diseases.”

Participating in the symposium were Eric Olson, PhD, chief scientific advisor at Vertex Pharmaceuticals; Mathew Pletcher, PhD, division head of gene therapy research and technical operations at Astellas Gene Therapies; Deanna Tucker, PharmD, senior medical science liaison at Sarepta Therapeutics; and Genine Winslow, MSc, president and CEO of Chameleon Biosciences.

Also on the panel: Beth Belluscio, MD, PhD, global clinical lead for rare neurological disorders at Pfizer; Oliver Danos, PhD, chief scientific officer at RegenXBio; Emil Kakkis, president and CEO at Ultragenyx Pharmaceutical; Alison Mcvie-Wylie, PhD, vice president and DMD disease area executive at Vertex; and Carl Morris, PhD, chief scientific officer at Solid Biosciences.


Gene therapy and gene editing symposium. Presented at: CureDuchenne 2021 Futures National Conference: October 9, 2021; Virtual.