One hundred and nine members of the U.S. House of Representatives signed a letter to the U.S. Food and Drug Administration (FDA) calling for the agency to immediately increase efforts to mobilize all available tools, resources, and authorities to advance new and more effective treatments for Duchenne muscular dystrophy.
The bipartisan appeal to the FDA to accelerate the process of review into new treatments for this ultimately fatal disease was initiated by Representatives Mike Fitzpatrick (Republican-Pennsylvania), Bill Keating (Democrat-Massachusetts), and Peter King (Republican-New York).
The Muscular Dystrophy Association (MDA) describes Duchenne muscular dystrophy (DMD), one of nine categories of muscular dystrophy, as a genetic disorder characterized by progressive muscle degeneration and weakness, caused by an absence of a protein called dystrophin in muscle cells. The lack causes muscles to become fragile and easily damaged. The onset of DMD symptoms is usually in early childhood, between ages 3 and 5, with progressively worsening disability that can cause death as early as age 25. The disease primarily affects boys.
Eteplirsen, by Sarepta Therapeutics, a morpholino antisense oligomer in development for the treatment of Duchenne muscular dystrophy amenable to exon 51 skipping of the dystrophin gene, was not mentioned directly in the lawmakers’ letter, but it is currently under FDA review.
The MDA notes that, while Duchenne muscular dystrophy was first described in the 1860s by the French neurologist Guillaume Benjamin Amand Duchenne, little was known about its cause or that of any category of muscular dystrophy until the 1986, when MDA-supported researchers identified a particular gene on the X chromosome, a mutation of which causes DMD. In 1987, the protein associated with this gene was identified and named dystrophin. DMD has an X-linked recessive inheritance pattern and is passed on by ‘carriers’ — mothers, who have a normal dystrophin gene on one X chromosome and an abnormal dystrophin gene on the other X chromosome. Most DMD carriers show no signs or symptoms of the disease, but a minority have symptoms that can range from mild skeletal muscle weakness or cardiac involvement to severe weakness or cardiac effects, beginning either in childhood or adulthood.
Due to advances in cardiac and respiratory care, life expectancy for young people with DMD is increasing, with a greater proportion of these young adults attending college, launching careers, getting married and having children. Survival into the early 30s is becoming more common, and some cases are known of men living with DMD into their 40s and 50s.
Researchers supported by MDA funding are actively pursuing several strategies for therapeutically addressing DMD, such as gene therapy, exon skipping, stop codon read-through, and gene repair, and clinical trials are underway for some of these approaches. Reps. Fitzpatrick, Keating, and King urge the FDA to fully utilize its authority and the tools Congress has provided in the Food and Drug Administration Safety and Innovation Act (FDASIA) to accelerate development of new therapies for treating persons with life-threatening and severely debilitating illnesses, especially ones for which no satisfactory alternative therapies exist, as is the case with Duchenne MD.
In their letter to the FDA, the 109 Congress members note that “the accelerated approval pathway outlined in Section 901 of FDASIA recognizes the limitations of developing drugs for rare diseases and gives the agency the flexibility to grant approval to rare disease treatments that have been shown to be safe and effective in fewer and smaller trials, while still requiring a larger confirmatory trial post-approval to confirm efficacy. This allows demonstrably safe therapies that treat an unmet medical need and appear to be efficacious, even with some uncertainty, to avoid the years of regulatory barriers and become accessible earlier to patients who otherwise have no other option. Consistent with FDA regulations, we believe it is ‘appropriate [for the FDA] to exercise the broadest flexibility in applying the statutory standards, while preserving appropriate guarantees for safety and effectiveness’ to new therapies intended to treat persons with life-threatening and severely-debilitating illnesses. As the FDA further notes, ‘the benefits of the drug need to be evaluated in light of the severity of the disease being treated.’ As Members of Congress representing constituents battling Duchenne, we wholeheartedly agree with this viewpoint and urge the FDA to ensure this flexibility is applied in reviewing all Duchenne candidate therapies.”
The full text of the letter can be found at jettfoundation.org/blog/109-congressional-representatives-stand-with-duchenne/.
“Our community is heartened to know that our congressional champions remain committed to ensuring the FDA uses the tools, authorities, and latitude necessary to review and clear safe, effective treatments,” Pat Furlong, founding president & CEO, Parent Project Muscular Dystrophy (PPMD) said in a release.
“Eteplirsen is the perfect example of a safe, efficacious drug that deserves the flexibility and approach provided to the agency in FDASIA,” adds Christine McSherry, founder and executive director of the Kingston, Massachusetts-based Jett Foundation. The nonprofit’s mission is to increase worldwide awareness of Duchenne muscular dystrophy with the purpose of raising and appropriating funds for research.
A 2013 open source study of eteplirsen, co-authored by Jerry R. Mendell, MD, and titled “Eteplirsen for the treatment of Duchenne muscular dystrophy” (Annals of Neurology Volume 74, Issue 5, pages 637–647, November 2013 DOI: 10.1002/ana.23982), concluded: “Eteplirsen restored dystrophin in the 30 and 50 mg/kg/wk cohorts, and in subsequently treated, placebo-controlled subjects. Duration, more than dose, accounted for dystrophin production, also resulting in ambulation stability. No severe adverse events were encountered.”
Over the past decade, the Jett Foundation has raised almost $6 million dollars for Duchenne research, and funds the Jett Program for Pediatric Neuromuscular Disorders (JPPND) at Mass General Hospital for Children (MGHfC), and Camp Promise — the only camp for individuals of all ages with muscular dystrophy and select neuromuscular diseases. The one-week overnight camp is provided free of charge to all campers and volunteers, with sites in Seattle, Philadelphia, and Denver. Additionally, the foundation provides advocacy services for families affected by Duchenne.
The Jett Foundation is a registered charity with 501(c)(3) status from the IRS; all donations are tax deductible. For more information, click here.
“Duchenne is a deadly and rare disease and we hope that the FDA will quickly complete its review and grant accelerated approval to this potential life-saving therapy,” adds Ms. McSherry, noting that the Jett Foundation and the Duchenne community are deeply appreciative of the Congress’ unprecedented statement, and looks forward to working together to speed up the drug approval process, the delivery of life-saving therapies, and ultimately finding a cure.
U.S. House of Representatives
The Muscular Dystrophy Association (MDA)
The Jett Foundation
Parent Project Muscular Dystrophy
Annals of Neurology