In First Trial of New Gene Therapy Program, Pfizer Doses First Duchenne Muscular Dystrophy Patient
DMD is muscle-wasting disease caused by a lack of the dystrophin protein, which helps keep muscle cells intact. It is the result of defects in the dystrophin gene. The disease mostly affects boys starting between the ages of three and five. By early teens, the patients typically can no longer walk, and the heart and lungs are affected. It generally results in an early death, often in the twenties, although some patients make it into their thirties and forties.
At the moment, the only approved drug is Sarepta Therapeutics’ Exondys 51 (eteplirsen). That drug is controversial and had a lengthy and dramatic trip to approval by the U.S. Food and Drug Administration (FDA). The drug is priced at about $300,000 per year based on a patient’s weight, and some payers have declined to cover it, while others have agreed to pay it on a limited basis.
Exondys 51 is only approved for a subset of DMD patients whose disease is caused by a specific mutation of the DMD gene that is amenable to its exon 51 skipping mechanism. The dystrophin gene is the largest gene in the human genome, and as such, is not a candidate for typical gene therapy, because it is too large for current vectors, which are typically adeno-associated viruses (AAV). Exondys 51 uses a mechanism that allows the genetic machinery that produced the protein, to “skip” over the damaged section of the gene.
Pfizer’s product is a mini-dystrophin gene therapy compound. The therapy uses a recombinant AAV9 capsid that carries a shortened version of the human dystrophin gene, i.e., “mini-dystrophin.”
The trial is a multi-center, open-label, non-randomized, ascending dose trial of a single infusion of the therapeutic. It expects to enroll about 12 boys between the ages of five and 12 who can still walk. In addition to studying the therapy’s safety and tolerability, it will evaluate dystrophin expression and distribution as well as clinical assessments of muscle strength, quality and function.
This trial is the first in Pfizer’s recombinant AAV-based gene therapy program that came out of the company’s acquisition in 2016 of Bamboo Therapeutics. It has recently made an expansion of the commercial-scale manufacturing facility in Sanford, North Carolina costing $100 million.
“Investment in this trial represents the culmination of years of research on behalf of patients by scientists at Pfizer and academic medical centers, along with the support of the DMD patient advocacy community, in the important quest to advance a program that could potentially change the trajectory of this debilitating disease,” said Greg LaRosa, senior vice president and chief scientific officer of Pfizer’s Rare Disease Research Unit, in a statement. “We’ve listened to the patient community and we know there is a dire need for treatment options; with this in mind, we have built on important scientific advances to design a therapy with the potential to deliver the mini-dystrophin gene to the body and address the underlying cause of DMD, regardless of mutation. This trial will assess the safety of this approach to gene therapy and could provide valuable data demonstrating its potential impact to slow down or stop the progression of DMD.”