Zevra Therapeutics recently received FDA approval for its drug Miplyffa, marking a significant development as it becomes the first approved therapy for Niemann-Pick disease type C (NPC), a severe and often fatal metabolic disorder. This approval is particularly impactful as NPC, a rare inherited condition, affects the central nervous system and can lead to death by adolescence.
NPC arises due to genetic mutations in NPC1 or NPC2 genes. These genes are crucial for cholesterol and fat transport within cells, and mutations lead to the accumulation of toxic substances that impair cellular function and cause organ damage. This damage manifests in symptoms such as worsening mobility, cognitive impairment, and difficulties with speech and swallowing. The prognosis for NPC patients is dire, with life expectancy around 13 years, and it is estimated that around 1,800 patients in the US and Europe combined suffer from NPC, with about 300 diagnosed cases in the US alone.
Miplyffa, which Zevra developed initially by Orphazyme, is a small molecule therapy in capsule form administered thrice daily, dosed according to patient weight. While the exact mechanism through which Miplyffa operates remains unclear, its therapeutic strategy involves slowing the progression of NPC symptoms rather than merely addressing the symptoms themselves.
The FDA’s approval focuses on the neurological impacts of NPC, with Miplyffa’s effectiveness assessed through a Phase 2/3 study involving 50 patients aged between 2 and 19. The study employed a specific rating scale to evaluate the severity of various NPC symptoms like walking, speech, swallowing, and motor skills, finding that Miplyffa users experienced slower disease progression compared to those on a placebo. Furthermore, additional support for the drug’s approval came from a four-year open-label extension study, which indicated improved patient outcomes versus historical data.
An interesting aspect of this approval is Miplyffa’s recommended use in conjunction with miglustat, another medication marketed under the name Zavesca by Johnson & Johnson for Gaucher disease and also for NPC in various international markets. Though miglustat isn’t approved for NPC in the US, its combined use with Miplyffa was a surprising element of the FDA’s approval. That being said, many NPC patients already receive miglustat, which suggests the combination requirement might not significantly limit the potential market.
However, side effects noted during studies included upper respiratory infections, diarrhea, and weight loss, and Miplyffa’s label carries warnings about possible hypersensitivity reactions such as hives and skin swelling. Analysts from William Blair highlighted that while the label’s specificity to neurological symptoms might not dampen the market potential, it could become a focal point in negotiations with payers, potentially affecting coverage decisions.
Previously turned down by the FDA in 2021 under Orphazyme, Miplyffa’s application faced a demand for additional data to establish its safety and efficacy. Zevra acquired the global rights to the drug in 2022 for $12.8 million and undertook further clinical investigations to support a new application. Zevra, which was formerly known as KemPharm, has since improved its financial standing, recently announcing a successful funding round and stating sufficient capital to support operations into early 2027.
The approval of Miplyffa also sees Zevra gaining a rare pediatric disease priority review voucher, a valuable asset that can be used to expedite the review process for future drug candidates, often sold to larger pharmaceutical companies for significant sums.
Looking forward, Zevra anticipates Miplyffa will be available in the US within eight to twelve weeks and has planned a conference call to discuss further details of the drug’s launch and availability. As the first FDA-approved treatment for NPC focusing specifically on the neurological symptoms, Miplyffa represents a beacon of hope for patients and families affected by this devastating disease.
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