[Updated 8/13/2020, 3:19 p.m.] Duchenne muscular dystrophy (DMD) patients whose disease is characterized by a particular genetic mutation now have a new treatment option following the FDA’s Wednesday approval of a drug developed by NS Pharma.
DMD is a genetic disorder that leaves patients unable to produce dystrophin, a protein key to muscle function. NS Pharma designed its drug, an antisense oligonucleotide called viltolarsen (Viltepso), to get a cell’s protein-making machinery to skip over the mutation so it still can produce dystrophin, albeit much less than those without any such mutations typically produce.
This rare mutation, which occurs in a section of DNA known as exon 53, affects about 8 percent of DMD patients, according to the FDA. Wednesday’s approval makes NS Pharma, the Paramus, NJ-based subsidiary of Japanese pharma company Nippon Shinyaku, the second company to have a drug OK’d by the agency for treating DMD patients with this particular mutation. A Sarepta Therapeutics (NASDAQ: SRPT) treatment, golodirsen (Vyondys 53), was approved late last year. The Cambridge, MA-based biotech also lays claim to the first ever FDA-approval for a DMD therapy, the exon 51-skipping drug eteplirsen (Exondys 51).
According to the FDA, DMD is diagnosed in about one out of every 3,600 male infants worldwide, though in rare cases it affects female infants, too. DMD patients develop progressive muscle weakness that first becomes apparent between the ages of 3 and 5. Exon-skipping drugs do not cure DMD. The approach is intended to boost dystrophin production enough to slow the disease’s progression.
The FDA’s review of viltolarsen was based on two Phase 2 studies, each enrolling 16 boys with a genetically confirmed DMD diagnosis. In one of those studies, eight patients were given weekly infusions of the NS Pharma drug at the recommended dose of 80 mg per kilogram of body weight. All of those boys showed an increase in dystrophin levels. The FDA says that their levels rose, on average, from 0.6 percent of what’s typical to 5.9 percent of normal levels at 25 weeks. Neither the company nor the FDA released the results of the second study.
The FDA says that the data from the first NS Pharma study demonstrated an increase in dystrophin production that is “reasonably likely to predict clinical benefit” in DMD patients who have a mutation that can be addressed by exon 53 skipping. But the regulator emphasized that the drug’s clinical benefit has not yet been established.
The accelerated approval, granted on a thinner body of evidence, means that NS Pharma must conduct an additional clinical trial to confirm that the drug is actually helping patients. That benefit will be assessed by measuring the time it takes for a DMD patient to stand. If the Phase 3 trial does not verify the drug’s benefit, the FDA can withdraw its approval. NS Pharma says its confirmatory study is already underway.
Small clinical trials have led to controversy and disagreement about the efficacy of DMD drugs. Eteplirsen’s review was based on a single study enrolling 12 boys, leading a 2015 FDA advisory panel to narrowly vote that Sarepta did not provide enough evidence to show the drug helped patients produce dystrophin. The agency bucked the advisory vote. But disagreement over the benefit of such DMD treatments didn’t end there, and the FDA rejected the company’s golodirsen nearly a year ago before reversing itself four months later. Some of the details about the extent of that dissent became public with the release of FDA documents in January.
In the two studies evaluating the NS Pharma drug, the most common side effects were upper respiratory tract infections, reactions at the injection site, cough, and fever. The FDA also cautions that kidney damage, some that is potentially fatal, has been observed in patients given other antisense oligonucleotides. The agency says physicians should monitor the kidney function of patients taking viltolarsen.
[Paragraph updated with additional drug price details.] A spokesman for NS Pharma said via email that viltolarsen will have a wholesale cost of $1,410 for each 250 mg vial. Since the drug is dosed according to a patients weight, the number of vials needed per treatment varies. But NS Pharma says its price is competitive with other antisense oligonucleotide drugs for DMD. Sarepta’s eteplirsen and golodirsen each cost about $300,000 annually. The NS Pharma drug is given as a weekly 60-minute infusion. Patients have the option to receive these infusions at home or in a healthcare facility. The company says it will help DMD patients and their physicians with a support program that includes webinars about the treatment.
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