The FDA on Friday approved a new spinal muscular atrophy drug that patients can take at home.
Risdiplam (Evrysdi) is a liquid medicine intended for daily use that was developed by Roche subsidiary Genentech in partnership with the SMA Foundation and South Plainfield, NJ-based PTC Therapeutics (NASDAQ: PTCT).
Regulators OK’d the drug, intended for daily administration via mouth or feeding tube, for patients with all forms of the disease starting at two months of age. In a prepared statement the FDA’s Billy Dunn, who heads its neuroscience unit, highlighted the dosing advantage.
“Evrysdi is the first drug for this disease that can be taken orally, providing an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than four years ago,” he said.
Spinal muscular atrophy is an inherited disorder caused by a defective SMN1 gene, which is responsible for producing the survival motor neuron (SMN) protein that’s crucial for muscles. The mutation impairs production of this protein, leading to the progressive muscle weakness that characterizes the disease. There are four main types of SMA, categorized according to severity.
The first SMA drug, Biogen’s nusinersen (Spinraza), was approved in 2016 for all ages and SMA types. Developed with San Diego-based Ionis Pharmaceuticals (NASDAQ: IONS), the RNA-based drug is administered three times yearly via an intrathecal (spinal) injection after four initial “loading” doses in the first two months of treatment.
Last year the FDA approved a second drug for the disease: A Novartis (NYSE: NVS) gene therapy called Zolgensma. However, the one-time intravenous therapy was OK’d only for children under age 2. The pharma giant is still testing an intrathecal version of the drug in older SMA patients, although the FDA stopped the company from further enrollment in one such study last October after concerning data from an animal study. Last month, in its announcement of second quarter 2020 financial results, Novartis said that discussions with the FDA about the partial clinical hold are continuing. The company still plans to submit an application for regulatory review next year.
Novartis priced Zolgensma at $2.1 million; Spinraza costs $750,000 in the first year and then $375,000 a year for the rest of a patient’s life. Risdiplam is priced per dose based on weight and age, the company told Xconomy. For example, a year of doses for a child who is younger than age 2 and weighs 15 pounds would run $100,000. Once patients reach 44 pounds, which typically occurs around age 6, the medicine’s cost is capped at $340,000 annually. Like Spinraza, the Roche oral therapy is a chronic treatment and patients will likely need to continue taking it for life.
All of the SMA drugs are designed to increase production of the SMN protein.
Data from two clinical trials underpinned the risdiplam application. In one trial, dubbed FIREFISH, seven of 17, or 41 percent of infants administered the drug could sit up without support for at least five seconds after 12 months of treatment. Untreated, infants with SMA aren’t expected to gain the ability to sit independently. In the other, called SUNFISH, which enrolled patients age 2 to age 25, those who received the drug saw an average improvement in motor function of 1.55 points on a scale that evaluates 32 different motor functions compared to those who received a placebo, who experienced an average increase of 1.36 points. The difference was unlikely attributable to chance.
In patients with later onset of the disease, the most common side effects reported were fever, diarrhea, and rash. Infants experienced similar side effects plus upper respiratory tract infections, pneumonia, constipation, and vomiting.
Risdiplam’s approval comes about two weeks ahead of the Aug. 24 deadline the FDA set for its decision. The company said the drug will become available for delivery to patients’ homes in the US later this month.
The treatment has been submitted for review by regulators in Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan, and Genentech described an application requesting review by the European Medicines Agency as “imminent.”