- Sarepta Therapeutics announced Thursday that another one of its medicines for a rare muscular illness has received approval from the Food and Drug Administration.
- The medicine, which will be sold as Amondys 45, is now cleared for use in patients with Duchenne muscular dystrophy who have specific mutations in the gene responsible for making dystrophin, a key muscle-building protein. Sarepta estimates 8% of Duchenne patients have mutations in exon 45, the part of the gene targeted by Amondys 45.
- Like its two other approved products, Sarepta’s latest offering is priced by weight, with treatment for a 20 kilogram child costing $300,000 per year. The addition of Amondys 45 means there are now medicines available to treat about 30% of Duchenne patients, according to data from CureDuchenne, a patient advocacy group sponsored in part by drugmakers like Sarepta.
The FDA’s review for Amondys 45 was relatively quiet compared to Sarepta’s two earlier products, known as Exondys 51 and Vyondys 53.
Exondys 51, in particular, stands as one of the most controversial approval decisions in the agency’s recent history. Clinical testing showed the drug provided small increases in dystrophin, while leaving its purported benefits on patients’ lives unclear. Several high-ranking officials within the FDA pushed for its rejection. But they were overruled by Janet Woodcock, the longtime head of the agency’s drug review division and, currently, its acting commissioner.
Woodcock’s decision not only cleared the path for Exondys 51, which became the first marketed drug specifically for Duchenne in 2016, but also set a precedent for subsequent medicines that work similarly.
Vyondys 53 followed, securing approval in 2019 after testing demonstrated similarly modest effects on dystrophin levels. That review also proved dramatic, as the FDA initially rejected Vyondys 53 because of safety concerns, only to about-face four months later. The agency then cleared Viltepso, a competing drug from Japan’s NS Pharma, one year later.
Amondys 45 appeared to simulate more dystrophin production than Exondys 51 and nearly as much as Vyondys 53 had in their respective clinical trials. In testing, patients’ dystrophin levels went from less than 1% at the start to about 2% after treatment with Amondys 45.
But it’s still unclear, as with Sarepta’s other drugs, whether Amondys 45 improves patients’ health outcomes. The FDA notes that while dystrophin production is “reasonably likely” to predict a clinical benefit like improved motor function, research has yet to prove Amondys 45 does so. A placebo-controlled, confirmatory trial known as ESSENCE is ongoing, but won’t produce results until 2024.
Each of Sarepta’s drugs is supposed to bind to the gene that encodes for dystrophin, but only at specific points that have been altered because of mutations. For Amondys, that point is exon 45. For the other two drugs, it’s exons 51 and 53, respectively. CureDuchenne estimates that 13% of patients are eligible for exon 51-skipping therapies, while exon 53- and 45-skipping therapies could each treat another 8% of the population.
Exondys 51 and Vyondys 53 helped to support Sarepta as the company built a lengthy list of drug programs, many of which focus on gene therapy research. Over the first nine months of 2020, Sarepta recorded $333 million in net product sales, a nearly 20% year-over-year increase, but posted a $365 million net loss. The company is scheduled to deliver its full 2020 earnings report next week.
Amondys 45 could lift Sarepta sales even further. Piper Sandler analyst Tyler Van Buren, for instance, expects the drug to bring in roughly $300 million in sales by 2025.
Yet the drug’s approval also comes at a potentially challenging time for the company. The August approval of Viltepso provided the first direct source of competition to a Sarepta drug. And more recently, Sarepta’s high-profile gene therapy program hit a major setback when treatment failed to significantly improve motor function in Duchenne patients.
The disappointing outcome was made all the more stinging as, the very same day, Pfizer disclosed that the first patient had been dosed in a large study of its competing Duchenne gene therapy. Sarepta shares fell more than 50% on the news, erasing about $6.5 billion from the company’s market value.
Following the Amondys 45 approval announcement, Sarepta stock was up a little more than 1% at market’s close Thursday, to trade a $85.25.