The Food and Drug Administration has granted accelerated approval to Vyondys 53 (golodirsen) to treat patients with Duchenne muscular dystrophy (DMD) who have a mutation of the dystrophin gene that is amenable to exon 53 skipping. About 8% of patients with DMD have this type of mutation. Further research is required to establish whether the antisense oligonucleotide provides clinical benefit, the agency said.
Separately, the agency approved the first newborn screening test for DMD.
DMD is a “rare and devastating disease,” said Billy Dunn, MD, acting director of the office of neuroscience in the FDA’s Center for Drug Evaluation and Research.
“Patients ... who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype,” Dr. Dunn said in a news release. “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data, and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
A surrogate endpoint
The FDA approved Vyondys 53 based on the surrogate endpoint of increased dystrophin production in the skeletal muscle in some patients treated with the drug. Sarepta Therapeutics, the developer of Vyondys 53, evaluated the treatment in a two-part clinical study. In the first part, eight patients with DMD received Vyondys 53, and four received placebo. In the second part, 25 patients, including the 12 patients from the first part, received open-label treatment. Dystrophin levels increased from 0.10% of normal at baseline to 1.02% of normal after at least 48 weeks of treatment.
A placebo-controlled, confirmatory trial is expected to conclude by 2024, the company said. If the trial does not confirm clinical benefit, the FDA could withdraw approval of the drug.
The most common side effects in patients who received Vyondys 53 include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms, and nausea. Some patients had hypersensitivity reactions. Renal toxicity occurred in animal studies of golodirsen, but not in the clinical studies. Renal toxicity, however, has occurred after treatment with other antisense oligonucleotides, the FDA noted.
Sarepta said Vyondys 53, an injection, would be available immediately. The drug is the company’s second RNA exon-skipping treatment for DMD. The FDA approved the first treatment, Exondys 51 (eteplirsen), in 2016. Together, the two drugs can treat about 20% of patients with DMD, the company said.
Newborn screening
On the same day, Dec. 12, 2019, the FDA authorized marketing of the first test to aid in newborn screening for DMD. Although authorization for the GSP Neonatal Creatine Kinase–MM kit enables laboratories to add this test to their newborn screening panel, it “does not signal a recommendation for DMD to be added ... as a condition for which newborn screening is recommended,” the agency said. In addition, the FDA noted that the kit is not meant to diagnose DMD or to screen for other muscular dystrophies.
The GSP Neonatal Creatine Kinase–MM kit measures the concentration of CK-MM, a type of protein that increases when there is muscle damage. The test measures CK-MM in dried blood samples collected from a newborn’s heel 24-48 hours after birth. Elevated levels may indicate DMD, but physicians must confirm the diagnosis using other methods, such as muscle biopsies, genetic testing, and other laboratory tests.
DMD primarily affects boys, and patients often do not have a family history of the condition. About 1 in 3,600 male live-born infants worldwide have DMD. Symptom onset usually occurs between the ages of 3 and 5 years.
The FDA reviewed the kit through the de novo premarket review pathway for low to moderate risk devices. In a clinical study of 3,041 newborns, the kit identified the four screened newborns who had DMD-causing genetic mutations. In addition, the test correctly identified 30 samples from newborns with clinically confirmed cases of DMD.
PerkinElmer developed the GSP Neonatal Creatine Kinase–MM kit.