The program reflects Otsuka’s commitment to facilitate early access to investigational medicines outside of a clinical trial, where permitted by local regulations, for people living with rare and life-threatening conditions who have limited or no available treatment options

PRINCETON, N.J. – September 22, 2026 – Otsuka Pharmaceutical Development & Commercialization, Inc. today announced the initiation of a global early access program (EAP) for ulefnersen, an investigational antisense oligonucleotide, for eligible people living with a genetic subtype of amyotrophic lateral sclerosis (ALS) known as FUS-ALS, caused by mutations in the fused in sarcoma (FUS) gene1, who have a confirmed genetic diagnosis and meet predefined program eligibility criteria. 

FUS-ALS is a rare form of ALS that is characterized by an earlier age of onset and is often rapidly progressive1. The disease progresses by eroding muscle function, impacting patients' independence as they lose their ability to move, speak, swallow, and breathe, ultimately leading to premature death2. There are currently no approved therapies specifically targeting the underlying genetic cause of FUS-ALS1, underscoring the significant unmet need for effective treatment options. For eligible people living with FUS-ALS who meet program criteria, the EAP offers a potential pathway to access the investigational medicine ulefnersen. Program availability, eligibility criteria, and application processes may vary by country and evolve over time. For the most up-to-date information on global availability, please visit www.otsuka-us.com/early-access-programs.

“Our approach to early access for ulefnersen is guided by an assessment of the available clinical evidence and our commitment to patient safety,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “For people living with FUS-ALS, their families, carers and advocates, decisions about treatment are deeply personal. This program is built on a foundation of safety, transparency and trust, with the goal of supporting informed decisions between eligible patients and their healthcare providers. As the ulefnersen program evolves, we remain committed to engaging openly with the FUS-ALS community and working closely with global and local health authorities.”

The ulefnersen EAP may be available to individuals with a confirmed genetic diagnosis of FUS-ALS who are unable to participate in an ongoing clinical trial and meet other predefined eligibility criteria. Otsuka is unable to accept direct requests for EAP access from patients or carers. All requests for early access must be initiated by a treating physician on behalf of the person living with FUS-ALS. Following review and potential acceptance of an application, additional steps will be required before treatment can begin, which may include applicable regulatory and ethics approvals, treatment-center readiness and patient-specific requirements. Potential timing from application to treatment will vary based on these factors. Treating physicians seeking information about eligibility criteria, or who wish to apply, should visit the Otsuka Early Access Portal.For additional questions, please contact EarlyAccessProgram@otsuka-us.com.

Ulefnersen is an investigational product and has not been approved by the U.S. FDA or any regulatory authority worldwide.

About FUS-ALS

FUS-ALS is a rare form of amyotrophic lateral sclerosis (ALS) that occurs across a broad age range, including pediatric and juvenile patients, and is often rapidly progressive1. It is a genetically defined subtype of ALS caused by pathogenic variants in the fused in sarcoma (FUS) gene, representing an estimated 0.6% of all ALS cases1. FUS mutations are more prevalent in juvenile and pediatric ALS, accounting for an estimated 43–52% of cases3. These mutations lead to the accumulation of toxic FUS protein in motor neurons, driving neurodegeneration2.

In early-onset and juvenile cases, disease progression can lead to respiratory failure and death, often within 1–2 years of symptom onset1. Diagnosis generally requires specialized clinical evaluation and confirmatory genetic testing4. There are currently no approved therapies specifically targeting the underlying genetic cause of FUS-ALS, underscoring the critical unmet need for effective treatment options1.

About Ulefnersen 

Ulefnersen is an investigational RNA-targeted medicine designed to bind FUS pre-messenger RNA (pre-mRNA) and reduce the production of FUS protein in people with FUS-ALS. Through reduction of FUS mRNA levels, ulefnersen is intended to decrease production of FUS protein, including the mutant forms that contribute to motor neuron degeneration in FUS-ALS. 

By targeting the underlying genetic cause of FUS-ALS, ulefnersen represents a potential FUS-targeted therapeutic approach for people living with the disease. Ulefnersen is administered via intrathecal injection, allowing direct delivery to the central nervous system. 

Ulefnersen is currently in clinical development and is being evaluated in the global Phase 1–3 FUSION (NCT04768972) trial in people living with FUS-ALS. In 2024, Otsuka Pharmaceutical entered into an exclusive global licensing agreement with Ionis Pharmaceuticals to further develop and commercialize ulefnersen. Ulefnersen was discovered and developed by Ionis.

Ulefnersen is an investigational product and has not been approved by the FDA or any regulatory authority worldwide.

Ulefnersen has been granted Fast Track designation for FUS-ALS by the U.S. Food and Drug Administration (FDA) and Orphan designation for ALS by the U.S. FDA, the European Medicines Agency (EMA) and Swissmedic. 

About Otsuka
Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.  

Otsuka America Pharmaceutical, Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc. are the US-based indirect subsidiaries of the global healthcare company Otsuka Pharmaceutical Co. Ltd. Otsuka’s US companies share a deep commitment to the development and commercialization of innovative products in the spaces of neuroscience, nephrology, and immunology. At our core is perseverance–a fierce determination to overcome any obstacle, regardless of setbacks, on behalf of patients, caregivers, and their loved ones. We will not be bound by doing what’s been done before. Learn more at www.otsuka-us.com.

References

  1. Moens T, Da Cruz S, Neumann M et al. Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications The Lancet Neurology, 24, 166-178
  2. U.S. Department of Health and Human Services. (2025, April 1). Silencing a faulty gene may uncover clues to rare forms of Als. National Institutes of Health. https://www.nih.gov/news-events/news-releases/silencing-faulty-gene-may-uncover-clues-rare-forms-als 
  3. Martins, I. (2020, April 17). FUS mutations cause most cases of ALS in adolescents, literature review finds. ALS News Today. https://alsnewstoday.com/news/fus-mutations-cause-most-cases-of-als-in-adolescents-literature-review-finds/ 
  4. Roggenbuck J, et al; ALS Genetic Testing and Counseling Guidelines Expert Panel. Ann Clin Transl Neurol. 2023;10(11):2074-2091