Perkinelmer Inc., of Waltham, Mass., has won a thumbs up from the U.S. FDA for its GSP Neonatal Creatine Kinase-MM kit. The assay is the first test approved in the U.S. for help in screening newborns for Duchenne muscular dystrophy (DMD), a rare but devastating genetic disorder.

An X chromosome-linked disorder, DMD occurs in roughly one in every 3,600 boys born worldwide and typically starts to manifest between the ages of three and five. The muscle-wasting disease is caused by a lack of dystrophin, a protein that strengthens muscle fibers and protects them from injury. As DMD progresses, patients often must use a wheelchair and experience serious heart and lung problems. Historically, most people with DMD did not live beyond their teens, but improvements in cardiac and respiratory care are extending life expectancy for many into their 30s and even 40s.

While there is no known cure for DMD, earlier screening and diagnosis could lead to improvements in quality of life by enabling earlier and more personalized treatment of symptoms. There are currently three FDA-approved drugs designed to treat patients with DMD: Sarepta Therapeutics Inc.’s Exondys 51 (eteplirsen) and Vyondys 53 (golodirsen) and Marathon Pharmaceuticals LLC’s Emflaza (deflazacort). FDA approval of Vyondys came at the same time as the Perkinelmer test.

Looking for telltale protein

The GSP Neonatal Creatine Kinase-MM test works by measuring the concentration of the protein CK-MM in dried blood sample collected from a heel prick when a newborn is 24 to 48 hours old. Creatine kinase is present in muscles, and increased amounts of CK-MM are released into the blood stream when muscles are damaged. High levels of CK-MM could mean a baby has DMD and should then be confirmed with muscle biopsies, genetic testing or other laboratory tests.

“Screening newborns not only prevents DMD patients and their families from an unnecessary diagnostic odyssey, but also ensures timely treatment for a disease that could otherwise go undetected for years,” said Linh Hoang, vice president of reproductive health at Perkinelmer. “By measuring the muscle-specific isoform, rather than total CK activity, Perkinelmer’s assay enables clinicians to identify babies with this condition faster and, most importantly, give them a better chance at improved health outcomes.”

Mei Baker, a professor in the Department of Pediatrics and co-director in the newborn screening laboratory at the University of Wisconsin School of Medicine and Public Health, agreed, stressing the advantageous nature of the test for clinicians and parents. “It’s a cost-effective way to screen for DMD with a two-tier testing approach: the first tier CK-MM assay allows identification of infants with excess muscle damage at birth, and the second tier DMD gene analysis would link the muscle damage to the genetic defect.”

De novo filing

The FDA approved the CD-MM assay via its de novo premarket pathway, which is intended for novel low-to-moderate-risk devices for which no legally marketed predicate exists. Products classified through this review process may serve as predicates for future 510(k) submissions.

To support its test, Perkinelmer submitted data from a study of 3,041 newborns whose dried blood samples were assayed for protein levels associated with DMD. Of those, the kit accurately picked out the four babies with mutations in the gene that causes DMD. The company also assayed 30 samples from newborns with clinically confirmed DMD, correctly identifying all of them.

“This authorization reflects our commitment to fostering innovation in devices to help inform and provide options to patients and their caregivers,” said Tim Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Early screening can help identify individuals who need additional follow-up and treatment.”

States can add test to newborn screening cards

The kit’s approval opens the door for states to include DMD among the battery of tests newborns typically undergo, such as phenylketonuria, cystic fibrosis and congenital heart disease. In recent years, there has been a push for states to align their newborn screening practices with the Recommended Uniform Screening Panel (RUSP) of core and secondary health conditions.

The FDA emphasized that including DMD in newborn screening panels is up to individual states. The Perkinelmer test should not be used to screen for other types of muscular dystrophy.

Perkinelmer’s pipeline includes the Vanadis noninvasive prenatal testing (NIPT) platform, which has been shown in clinical trials to accurately detect several chromosomal abnormalities. In an analysis of plasma samples from 1,200 pregnant women, which included 158 fetal anomalies, the fully automated, nonsequencing, cell-free DNA screening assay showed high sensitivity and specificity for Down syndrome, Edwards syndrome and Patau syndrome. The platform received CE mark approval in Europe in November 2018, but has not yet received FDA clearance.