RARE Daily

Acadia Acquires Ex-North American Rights to Trofinetide; Global Rights to Neuren’s Therapy in Rett and Fragile X Syndromes

July 14, 2023

Rare Daily Staff

Acadia Pharmaceuticals expanded its current licensing agreement for trofinetide with Neuren Pharmaceuticals to acquire ex-North American rights to the drug, as well as global rights in Rett syndrome and Fragile X syndrome to Neuren’s development candidate NNZ-2591.

In April of this year, Acadia launched trofinetide in the United States under the brand name Daybue as the first and only drug approved for the treatment of Rett syndrome.

“This expanded worldwide agreement solidifies Acadia’s position as the global leader in addressing the unmet needs of people with Rett syndrome,” said Steve Davis, president and CEO of Acadia Pharmaceuticals.

In addition to expanding access to trofinetide outside of North America, this agreement gives Acadia exclusive worldwide rights to NNZ-2591 in both Rett syndrome and Fragile X syndrome. NNZ-2591 is an investigational synthetic analogue of cyclo-glycyl-proline (cGP) which results from the breakdown of human insulin-like growth factor 1 (IGF-1). NNZ-2591 is currently under development by Neuren in four other rare neurodevelopmental syndromes.

Acadia said execution of the agreement advances the company’s corporate strategy to expand its rare disease business and the global potential of Acadia’s current development portfolio.

Acadia intends to submit a New Drug Submission for trofinetide in Canada in the next 18 months with plans for Europe, Asia, and other regions to be announced at a later date.

Under the terms of the expanded agreement, Neuren will receive an upfront payment of $100 million and is eligible to receive additional potential downstream milestone and royalty payments earned separately for trofinetide and NNZ-2591.

Neuren will also receive tiered royalties from the mid-teens to low-twenties percent of trofinetide net sales outside of North America. In North America, all milestones and royalties for trofinetide remain unchanged from Acadia’s previously existing North American license agreement with Neuren. Potential future payments to Neuren related to NNZ-2591 in Rett syndrome and Fragile X syndrome are identical to the payments for trofinetide in each of North America and outside North America.

Rett syndrome is a rare, complex, neurodevelopmental disorder that may occur over four stages and affects approximately 6,000 to 9,000 patients in the United States, with approximately 4,500 patients currently diagnosed according to an analysis of healthcare claims data. Worldwide, incidence rates for Rett syndrome are similar in countries across the globe, with prevalence varying according to population size, with the number of patients in Europe estimated to be larger and that of Japan’s smaller.

A child with Rett syndrome exhibits an early period of apparently normal development until six to 18 months, when their skills seem to slow down or stagnate. This is typically followed by a duration of regression when the child loses acquired communication skills and purposeful hand use. The child may then experience a plateau period in which they show mild recovery in cognitive interests, but body movements remain severely diminished. As they age, those living with Rett may continue to experience a stage of motor deterioration which can last the rest of the patient’s life. Rett syndrome is typically caused by a genetic mutation of the MECP2 gene. In preclinical studies, deficiency in MeCP2 function has been shown to lead to impairment in synaptic communication, and the deficits in synaptic function may be associated with Rett manifestations. Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities. Most Rett patients typically live into adulthood and require round-the-clock care.

Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate. The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase branching of dendrites and synaptic plasticity signals.

Fragile X syndrome is the most common inherited cause of intellectual disability and the most commonly known cause of autism. Fragile X syndrome is due to a gene mutation on the X chromosome that impacts the FMRP protein, which is responsible for regulating the synapses of nerve cells. The full mutation causes Fragile X syndrome. It is estimated that between one in 4,000 and one in 7,000 males and between one in 6,000 and one in 11,000 females have the full mutation. Generally, males are more severely affected, with approximately 50 percent of the females having some features of the syndrome. Clinically, Fragile X syndrome is characterized by intellectual handicap, hyperactivity and attentional problems, autistic symptoms, anxiety, emotional lability and epilepsy. Currently, there are no medicines approved for the treatment of Fragile X syndrome.

Photo: Steve Davis, president and CEO of Acadia Pharmaceuticals


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