Rare diseases, affecting fewer than 200,000 people in the U.S., pose significant challenges due to their low prevalence. According to the NIH, there are over 7,000 known rare diseases, each with unique symptoms and treatments. For example, cystic fibrosis, a genetic disease affecting the lungs, often goes misdiagnosed. The lack of large patient populations hinders drug development, limiting treatment options. However, therapeutic advancements have shown promise in treating some rare diseases, offering hope for the future.
This week FDA approved two new drugs against a Niemann Pick Disease Type C, a rare and progressive genetic disorder. Zevra Therapeutics’ Miplyffa (arimoclomol) got its approval on 20th September, whereas IntraBio’s Aqneursa (levacetylleucine) was greenlit on 24th September.
What is Niemann Pick Disease Type C?
Niemann-Pick disease type C (NPC) is a rare and devastating genetic disorder that affects approximately 1 in 150,000 individuals worldwide. It causes a toxic buildup of lipids, including cholesterol and glycosphingolipids, within cells due to impaired intracellular transport. This leads to a range of debilitating symptoms, which can vary depending on the age of onset. Infants may experience liver or spleen enlargement, jaundice, and poor feeding, while children and adolescents may suffer from developmental delays, loss of motor skills, seizures, and declining cognitive function. As the disease progresses, individuals may experience ataxia, dysarthria, dysphagia, and further cognitive decline.
NPC is caused by mutations in the NPC1 (95%) or NPC2 (5%) genes, inherited in an autosomal recessive pattern. Diagnosis involves clinical evaluation, genetic testing, and biochemical tests such as filipin staining. While there is no cure, treatment focuses on alleviating symptoms and improving quality of life through supportive care, medications and experimental therapies such as gene therapy and histone deacetylase inhibitors. The prognosis varies depending on the age of onset and severity, with infants typically not surviving beyond 5 years and late-onset forms experiencing slower progression. Despite the challenges, researchers continue to explore new treatments to combat this relentless disease.
How do the new drugs work against NPC?
Arimoclomolis an oral medication that helps treat Niemann-Pick disease type C (NPC). The mode of action is yet to be determined. Experimentally, the molecule can induce the heat shock proteins which might stabilize the membranes around lipid-filled lysosomes and slow the progression of NPC. Combined with miglustat It works by blocking an enzyme that produces harmful fats that build up in cells. By stopping this enzyme, Arimoclomol might reduce excess of fat storage, helping cells work better and slowing down the disease.
Aqneursa, also known as levacetylleucine, is an oral medication that targets the neurological manifestations of Niemann-Pick disease type C (NPC). It has been shown to improve neurological signs and symptoms, with functional benefits evident within 12 weeks, particularly in motor and speech disturbances.
Image Source: Avraneel Paul
Clinical Studies, Efficacy and and Side Effects
Arimoclomol went through a randomized, double-blind, placebo-controlled trial involving 50 patients aging from 2 to 19 years. To study the combinatorial effect, 37 out of 50 patients received a prior treatment of miglustat. 33% of the patients orally received placaebo, 3 times a day. 5-domain NPC Clinical Severity Scale was considered as the primary endpoint of the trial.
In 2021, Arimoclomol showed a 1.4-point benefit over placebo, but faced rejection by FDA, as the small scale of improvement was considered insignificant. Later this year, Zevra after occupying Orphazyme performed the trial of Arimoclomol with a background treatment of miglustat and a showed a promising 2.2-point benefit compared the placebo with the same background treatment.
Aqneursa (levacetylleucine) went through a phase III trial with 60 patients. The change in Scale for the Assessment and Rating of Ataxia (SARA), a 40-point measure of loss of muscle function, was considered as the endpoint. A group of patients received Aqneursa followed by placebo, whereas the other group received in the reverse order. 85% of the patients used miglustat as a background treatment. After 12 weeks of treatment Aqneursa showed a significant improvement compared to placebo and was approved as a monotherapy by FDA.
Hypersensitivity Reactions and Embryofetal Toxicity, along with Upper respiratory tract infection, diarrhea, and decreased weight are be the potential risks of Arimoclomol treatment. Most common adverse effects of Aqneursa include are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.
The FDA approval of the two drugs brings hope to Niemann-Pick disease type C patients and families. These clinical trials show promising result and hope that the treatment will slow disease progression, marking a milestone in rare disease research. Miplyffa and Aqneursa’s clinical success paves the way for further innovation, offering a brighter future for the NPC community.
Dr. Avraneel Paul, Ph.D.
Sources
- https://rarediseases.org/rare-diseases/niemann-pick-disease-type-
- https://investors.kempharm.com/news-releases/news-release-details/zevra-therapeutics-miplyffatm-arimoclomol-receives-us-fda
Disclaimer
The editors take care to share authentic information. In case of any discrepancies please write to newsletter@medness.org
The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of MedNess. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open-source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for MedNess. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
MedNess is a part of STEMPeers® which is a 501(c)(3) organization registered in PA as PhD Career Support Group. The organization helps create a growing network of STEM scientists that is involved in peer-to-peer mentoring and support.
