Casimersen (Amondys 45) is approved to treat Duchenne muscular dystrophy skipping, the FDA announced Thursday.
Like two other exon-skipping RNA therapies for DMD approved in recent years -- the controversial eteplirsen (Exondys 51) and golodirsen (Vyondys 53) -- the FDA's decision was based on casimersen's ability to increase dystrophin production in skeletal muscle. Clinical benefit of the drugs, including improved motor function, has not been established.
"After years of scientific commitment, investment and development, the approval of Amondys 45, Sarepta's third approved RNA therapy, offers treatment to the 8% of the DMD community who have a confirmed exon 45 amenable mutation," said Doug Ingram, president and CEO of drugmaker Sarepta Therapeutics, . "Along with our other approved RNA therapies, we can now offer treatment options for nearly 30% of Duchenne patients in the U.S." Both eteplirsen and golodirsen are Sarepta products.
DMD is a rare disease caused by an absence of dystrophin. First symptoms of the disorder usually are seen when patients are 3 to 5 years old and worsen over time. People with DMD progressively lose their ability to perform activities independently and often require a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions may occur.
Casimersen, an antisense oligonucleotide, won approval through the for drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments. Under this pathway, approval can be based on studies that show a drug has an effect on a .
In the casimersen study, the surrogate endpoint was skeletal muscle dystrophin production. The double-blind trial randomized 43 patients -- 7 to 20 years old, all male -- 2:1 to receive either intravenous casimersen (30 mg/kg) or placebo. Participants who received casimersen showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment compared with those in the placebo group.
Most common side effects observed in the casimersen group were upper respiratory tract infections, cough, fever, headache, joint pain, and throat pain. While kidney toxicity was not seen in the casimersen clinical studies, it was observed in nonclinical studies. Kidney toxicity, including potentially fatal glomerulonephritis, has been observed with some antisense oligonucleotides, and kidney function should be monitored in patients taking casimersen, the FDA warned.
Further study is required to verify and describe anticipated clinical benefits of taking casimersen, the agency added. Sarepta is conducting the to evaluate the safety and efficacy of the treatment in ambulatory DMD patients.