For Zevra Therapeutics and its rare neurodegenerative disease med arimoclomol, the second time’s the charm.
Friday, the FDA approved Zevra’s arimoclomol capsules to treat the rare lysosomal storage disorder Niemann-Pick disease type C (NPC) in conjunction with Johnson & Johnson’s enzyme inhibitor miglustat, also known as Zavesca.
Arimoclomol, which will fly under the brand name Miplyffa, is now the first FDA-approved therapy for NPC, Zevra said in a release.
The drug is specifically cleared to treat neurological manifestations of NPC in adults and kids ages 2 and up. Zevra picked up the green light after arimoclomol was rejected by the FDA in 2021 over aspects of the lone clinical trial used to support the drug’s application.
NPC, which Zevra estimates affects nearly 900 people in the U.S., prevents the body from moving and using cholesterol and other lipids in cells. This causes a buildup of cholesterol and other lipids in the liver, spleen or lungs. People with NPC only live for about 13 years on average, the FDA noted in a separate release.
The disease can weigh heavily on patients’ speech, cognition, swallowing, movement and fine motor skills, Zevra said.
With an approval in hand, Zevra says it will “immediately” kick off launch activities for Miplyffa, which the company expects to hit U.S. pharmacy shelves in the next eight to 12 weeks.
To help people with NPC get their hands on the drug, Zevra has launched a patient support program dubbed AmplifyAssist, which will feature personalized insurance coverage education and support, copay and alternate funding assistance and more.
The company has also won a priority review voucher in conjunction with the green light.
The FDA’s approval leveraged data from a yearlong, placebo-controlled study in patients 2 to 19 years old. Seventy-six percent of patients in the Miplyffa group and 81% of those in the placebo cohort received miglustat as part of their routine care.
In the trial, Miplyffa plus miglustat halted disease progression through 12 months of treatment as shown by a 0.2 point decrease from baseline on the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS). By comparison, patients in the trial’s control arm saw 1.9 points of progression on the scale, which examines metrics identified as most relevant for NPC patients, including ambulation, speech, swallowing and fine motor skills, according to the FDA.
Zevra also furnished the FDA with additional data from a 48-month, open-label extension study that suggested improved outcomes on Miplyffa according to a natural history comparison of the disease from the National Institutes of Health.
Miplyffa is taken by mouth three times a day, and its dosing is dependent upon a patient’s body weight. The drug’s prescribing info contains a warning for hypersensitivity reactions including hives and swelling under the skin, the FDA said.
The original approval bid for Miplyffa hinged on data from the study CT-ORZYNPC-002, which utilized a different measure of disease severity known as the 5-domain NPC Clinical Severity Scale (5DNPCCSS).
In the FDA’s 2021 complete response letter, the agency challenged the interpretability of that particular scale, specifically bringing its validity and reliability into question.
Zevra ultimately returned to the FDA with a rescored scale and more results from its study in December 2023.
Miplyffa’s approval prospects started looking up following a meeting of the FDA’s Genetic Metabolic Diseases Advisory Committee earlier this summer. At the time, the outside experts voted 11 to 5 in favor of the efficacy of Zevra’s drug.
Despite the overall favorable vote, many of the panel members were torn on the medicines’ efficacy package.
“I voted yes but it was a very reluctant yes,” private consultant Jonathan Mink, M.D., Ph.D., said during the meeting. “I found the effect size to be small and the strength of the data to be weak, but overall the bulk of the data favored a slightly positive effect.”
Many panelists pointed to the high unmet need in NPC in justifying their "yes" votes.
While Miplyffa will have the market to itself when it comes to neurological manifestations of NPC, it’s not entirely alone in the field.
Back in August 2022, Sanofi scored an FDA nod for its infusion Xenpozyme for non-central nervous system manifestations of Niemann-Pick, also known as acid sphingomyelinase deficiency (ASMD).
Xenpozyme is a hydraulic lysosomal enzyme replacement therapy that reduces the accumulation of sphingomyelin. The drug isn’t thought to be able to cross the blood-brain barrier or modulate CNS manifestations of ASMD, Sanofi said at the time.