Rare Daily Staff

Acadia Pharmaceuticals entered into an exclusive North American license agreement with Neuren Pharmaceuticals for the development and commercialization of trofinetide, Neuren’s experimental drug for Rett syndrome and other indications.

Rett syndrome is a debilitating neurological disorder that occurs primarily in females following apparently normal development for the first six months of life. Rett syndrome has been most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. Typically, between six to eighteen months of age, patients experience a period of rapid decline with loss of purposeful hand use and spoken communication and inability to independently conduct activities of daily living. Symptoms also include seizures, disorganized breathing patterns, an abnormal side-to-side curvature of the spine, and sleep disturbances. Currently, there are no approved medicines approved for the treatment of Rett syndrome.

Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and supporting synaptic function. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical for both normal development and for response to injury and disease. Trofinetide has been granted U.S. Food and Drug Administration Fast Track status and Orphan Drug designation in the United States and Europe.

Under the terms of the agreement, Acadia will pay Neuren $10 million up front and potential milestones of $455 million. Neuren retains rights to develop and commercialize trofinetide for all indications outside of North America. In addition, Neuren is eligible to receive tiered, escalating, double-digit percentage royalties on net sales of trofinetide in North America and one third of the market value of any Rare Pediatric Disease Priority Review Voucher, if awarded by the U.S. FDA upon approval of a New Drug Application for trofinetide.

The potential milestone payments to Neuren consist of $105 million subject to achievement of development milestones in Rett syndrome and Fragile X syndrome, the most common inherited cause of intellectual disability and the most common known cause of autism. Up to an additional $350 million in milestone payments are subject to achievement of thresholds of annual net sales of trofinetide in North America.

Acadia will fund and execute the remaining development for trofinetide in Rett syndrome in North America, except for the completion by Neuren of certain in-progress preparatory activities. Acadia and Neuren will form a Joint Steering Committee to direct the development of trofinetide in all indications, including the next clinical trial for Fragile X syndrome.

Any data and regulatory filings generated by Acadia or Neuren may be used by either party for the development and commercialization of trofinetide in their respective territories. Acadia has a right of first negotiation to acquire a license to develop and commercialize trofinetide outside North America. Neuren has an obligation not to develop a competing product in indications for which Acadia develops and commercializes trofinetide.

Acadia plans to initiate a phase 3 randomized, double-blind placebo-controlled study evaluating trofinetide in the second half of 2019 following completion of additional manufacturing activities. This study will evaluate trofinetide and placebo in approximately 180 girls with Rett syndrome and will measure the, a caregiver assessment, and the Clinical Global Impression of Improvement, a physician assessment, as co-primary efficacy endpoints.

Neuren conducted a Phase 2 double-blind placebo-controlled dose ranging study in girls aged 5 to 15 years with Rett syndrome, in which statistically significant and clinically meaningful improvement was demonstrated on the Rett Syndrome Behavior Questionnaire and Clinical Global Impression of Improvement assessments. This followed positive trends observed in an earlier phase 2 trial in adolescents and adults aged 16 to 45 years with Rett syndrome. In addition, Neuren has completed an exploratory study in Fragile X syndrome.

“A potential treatment for Rett syndrome is a perfect fit with Acadia’s mission to develop novel therapies to improve the lives of patients with central nervous system disorders,” said Serge Stankovic, executive vice president, head of research and development for Acadia. “Today there are no approved treatments for the girls and women suffering from Rett syndrome. We look forward to initiating a phase 3 study in the second half of 2019 to further explore the potential benefits of trofinetide for patients and their caregivers.”

August 7, 2018
Photo: Serge Stankovic, executive vice president, head of research and development for Acadia