5 Rare Diseases That Now Have Their First FDA-Approved Treatments

Since Rare Disease Day last year, several rare diseases have gained their first-ever FDA-approved drug, signifying progress in closing treatment gaps for these conditions.

1. Niemann-Pick Disease, Type C: Arimoclomol (Miplyffa)

Patients with Neimann-Pick disease, type C (NPC), received their first FDA-approved treatment in September.¹ Children with the rare genetic condition live for an average of 13 years and experience progressive neurological symptoms. In combination with miglustat, arimoclomol aims to mitigate the neurological symptoms of NPC with an indication for patients at least 2 years old.

Days after Zevra Therapeutics’ arimoclomol approval, IntraBio’s levacetylleucine (Aqneursa) was approved for the treatment of neurological symptoms associated with the condition in patients weighing at least 15 kg.² According to Laurie Turner, family services manager at the National Niemann-Pick Disease Foundation, the approval of these therapies represents a "tremendous milestone" for a community that has been without FDA-approved options for too long.

Rare Disease Day is celebrated on the last day of February each year. | Image Credit: © Chinnapong - stock.adobe.comeg

2. WHIM Syndrome: Mavorixafor (Xolremdi)

Prior to April, patients living with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM syndrome) lacked an FDA-approved treatment option, making mavorixafor capsules (Xolremdi; X4 Pharmaceuticals) the first approved therapy for patients 12 years and older.³ The selective CXC chemokine receptor 4 (CXCR4) antagonist was designed to increase the number of circulating mature neutrophils and lymphocytes to address the pathway dysfunction causing the rare and chronic neutropenic disorder.

Traditionally, care for patients with WHIM syndrome has been supportive, aimed at managing symptoms, instead of targeting the CXCR4 pathway, according to Teresa K. Tarrant, MD, associate professor of medicine, rheumatology, and immunology at Duke University School of Medicine, and lead investigator of the phase 3 clinical trial, 4WHIM (NCT03995108), that bolstered the agency's decision. "We now have a targeted treatment that has demonstrated the ability to elevate [absolute neutrophil counts] and [absolute lymphocyte counts], increasing ability to fight infections," she stated.

3. Familial Chylomicronemia Syndrome: Olezarsen (Tryngolza)

In December, olezarsen (Tryngolza; Ionis Pharmaceuticals) became the first and only FDA-approved drug option for patients with familial chylomicronemia syndrome.⁴ The agency approved olexarsen as an adjunct to diet in adults with the rare genetic condition. Patients with familial chylomicronemia syndrome adhere to significant lifestyle changes as a preventive effort; often nonresponsive to triglyceride-lowering treatment, they're highly susceptible to acute pancreatitis and other health consequences.

Olezarsen, an antisense oligonucleotide that inhibits the production of apolipoprotein C-III (APOC3), significantly reduced fasting triglyceride levels and APOC3 levels in the phase 3 BALANCE trial, supporting the FDA approval. For a patient population that previously had no therapeutic options with only an extremely strict diet and lifestyle changes to rely on, BALANCE trial investigator Alan Brown, MD, of Rosalind Franklin University of Medicine and Science, emphasized the importance of having a treatment option that decreases the risk of potentially life-threatening acute pancreatitis events for the first time.

4. Cerebrotendinous Xanthomatosis: Chenodiol (Ctexli)

With last week's approval of chenodiol tablets (Ctexli; Mirum Pharmaceuticals), patients living with cerebrotendinous xanthomatosis (CTX) gained their first FDA-approved drug.⁵ CTX is an extremely rare genetic metabolic disorder that is caused by a mutation in the CYP27A1 gene, leading to reduced bile acid production in the liver and an inability to break down cholesterol adequately. Without treatment organ damage occurs and patients experience chronic diarrhea, juvenile bilateral cataracts, tendon xanthomas, and neurologic deterioration.

By replacing deficient levels in one of the key bile acids, chenodiol reduces the abnormal deposits of cholesterol metabolites responsible for CTX-related clinical abnormalities. Data from the phase 3 RESTORE (NCT04270682) supported the FDA approval by meeting its primary end point—change in the urinary bile alcohol 5β-cholestane-3α,7α,12α,23S,25-pentol—and its secondary efficacy end points measuring changes in plasma cholestanol and 7a-hydroxy-4-cholesten-3-one. Now, physicians and patients living with this progressive multisystemic disorder have a safe and effective treatment option to help mitigate the condition's impact on their quality of life.

5. Metachromatic Leukodystrophy: Arsa-cel (Lenmeldy)

Following priority review, orphan drug, rare pediatric disease, and regenerative medicine advanced therapy approvals, pediatric patients with metachromatic leukodystrophy gained an FDA-approved gene therapy, atidarsagene autotemcel, or arsa-cel (Lenmeldy; Orchard Therapeutics), in March.⁶ This marked the first approved treatment for patients with the rare inherited lysosomal disease; a population whose symptoms commonly present before the age of 2 and live for 5 to 8 years as symptoms progress after onset. The indication includes pediatric patients who have presymptomatic late infantile, presymptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy.

Arsa-cel utilizes a patient’s genetically modified hematopoietic (blood) stem cells that now include functional copies of the ARSA gene introduced via a lentiviral vector and engraft within bone marrow. Following a conditioning regimen of high-dose chemotherapy, arsa-cel is designed to slow disease progression and is administered in a single infusion. The FDA decision was based on data from 2 trials and an expanded access program evaluating the therapy's safety and effectiveness, with a primary end point of severe motor impairment-free survival. Results showed a significant reduction in the risk of death and severe motor impairment following administration of arsa-cel compared with untreated children.

References

1. Iapoce C. FDA approves first drug for Niemann-Pick disease, type C. HCP Live. September 20, 2024. Accessed February 27, 2025. https://www.hcplive.com/view/fda-approves-arimoclomol-first-drug-for-niemann-pick-disease-type-c

2. Iapoce C. FDA approves levacetylleucine for Niemann-Pick disease, type C. HCP Live. September 24, 2024. Accessed February 27, 2025. https://www.hcplive.com/view/fda-approves-levacetylleucine-for-niemann-pick-disease-type-c

3. McGovern G. FDA approves mavorixafor capsules to treat patients with WHIM syndrome. Pharmacy Times. April 29, 2024. Accessed February 27, 2025. https://www.pharmacytimes.com/view/fda-approves-mavorixafor-capsules-to-treat-patients-with-whim-syndrome

4. Iapoce C. Olezarsen earns first-ever FDA approval for familial chylomicronemia syndrome. HCP Live. December 19, 2024. Accessed February 27, 2025. https://www.hcplive.com/view/olezarsen-earns-first-ever-fda-approval-for-familial-chylomicronemia-syndrome

5. McGovern G. Chenodiol first treatment for cerebrotendinous xanthomatosis receives FDA approval. Pharmacy Times. February 21, 2025. Accessed February 27, 2025. https://www.pharmacytimes.com/view/chenodiol-first-treatment-for-cerebrotendinous-xanthomatosis-receives-fda-approval

6. Shaw M. FDA approves arsa-cel for metachromatic leukodystrophy. AJMC^®. March 19, 2024. Accessed February 27, 2025. https://www.ajmc.com/view/fda-approves-arsa-cel-for-metachromatic-leukodystrophy