FDA Authorizes First Duchenne Muscular Dystrophy Newborn Screening Test

Tim Stenzel, MD, PhD

The first newborn screening test for Duchenne muscular dystrophy (DMD) has been authorized by the FDA, allowing laboratories across the US to add the GSP Neonatal Creatine Kinase-MM kit to their newborn screening panels if they choose to do so.¹

Notably, this authorization is not a recommendation for the DMD screen to be added to the Recommended Uniform Screening Panel (RUSP) that has been developed through a collaboration between the federal Advisory Committee on Heritable Disorders in Newborns and Children and the American College of Medical Genetics, as well as other governmental, non-governmental, advocacy, and private partners.

Earlier this year, a panel from the Muscular Dystrophy Association called for DMD to be added to the RUSP, noting that “because 66% of cases are the result of maternal carriers of dystrophin mutations, early diagnosis of the family proband may facilitate appropriate counseling to help prevent additional boys in the same family from being affected by the disorder,” they wrote.

Newborn screening is made up of a series of tests to help identify serious diseases and conditions in newborns. While the list of diseases and conditions tested for varies from state to state, the RUSP contains a list of core and secondary conditions that the US Department of Health and Human Services recommends that all states include on their newborn screening panel. The DMD screening kit has not been added to the RUSP at this time.

The test, which measures the concentration of the CK-MM protein, is not intended for the diagnosis of DMD or for screening of other types of muscular dystrophy. Elevated levels of CK-MM in the blood are associated with muscle damage, which may be indicative of DMD. A positive DMD screen on the newborn panel should be confirmed with muscle biopsy, as well as other genetic and laboratory testing.

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“Diagnostics that can safely and effectively screen newborns can help health care professionals identify and discuss potential treatment options with parents and caregivers before symptoms or effects on a baby’s health may be noticeable,” said Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement.¹ “This authorization reflects our commitment to fostering innovation in devices to help inform and provide options to patients and their caregivers. Early screening can help identify individuals who need additional follow up or treatment.”

While rare, DMD is the most common type of muscular dystrophy, occurring in approximately 1 in 3600 male live-born infants worldwide. Symptoms typically emerge around age 3 to 5 and progressively worsen over time, with most patients bound to a wheelchair by their teens. The progressive loss of healthy muscle tissue contributes to life-threatening cardiovascular and respiratory conditions. The typical lifespan of a patient with DMD is 20 to 30 years, although life expectancy varies with disease severity.

The screening kit serves a significant unmet need, as the CDC has advised that early diagnosis of DMD may lead to more personalized treatment and may improve the odds that a patient reaches his or her full potential. Notably, an average 2.5-year gap has been reported from the time that a parent or caregiver first notices signs of DMD and receiving a confirmed DMD diagnosis.

DMD has been in the spotlight in the last several years, as several treatments for the disease fight to make their way through regulatory filings. The first, albeit controversial, treatment for DMD, eteplirsen (Exondys 51; Sarepta), was approved by the FDA in 2016 for patients with a dystrophin gene mutation amenable to exon 51 skipping.² Since that approval, several drugs have tried—and some failed—to slow progression of the disease and preserve function. Most notably, the FDA recently rejected the NDA for golodirsen, Sarepta’s latest candidate for patients with DMD amenable to exon 53 skipping. Other pharmaceutical companies have had equally as bad a go, with Solid Biosciences’ investigational gene therapy candidate SGT-001 put on hold several times for safety concerns, and Roche choosing to discontinue its development of RG6206, an anti-myostatin adnectin protein agent that was in phase 2/3 trials. Others, including Wave Life Sciences’ suvodirsen, Catabasis Pharmaceuticals’ edasalonexent, and FibroGen’s pamrevlumab, appear to be on a better track, but only time will tell how these clinical trials play out.

REFERENCES

1. FDA authorizes first test to aid in newborn screening for Duchenne Muscular Dystrophy [news release]. US FDA. December 12, 2019. fda.gov/news-events/press-announcements/fda-authorizes-first-test-aid-newborn-screening-duchenne-muscular-dystrophy. Accessed December 12, 2019.

2. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy [news release]. US FDA. September 19, 2019. fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy. Accessed December 12, 2019.