SAN DIEGO & MELBOURNE, Australia--(BUSINESS WIRE)--ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) and Neuren Pharmaceuticals Limited (ASX: NEU) announced today that they have entered into an exclusive North American License Agreement for the development and commercialization of trofinetide for Rett syndrome and other indications. Neuren retains rights to develop and commercialize trofinetide for all indications outside of North America.
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 Rett Syndrome Behavior Questionnaire (RSBQ), a caregiver assessment, and the Clinical Global Impression of Improvement (CGI-I), a physician assessment, as co-primary efficacy endpoints.
“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, M.D., M.S.P.H, Executive Vice President, Head of Research and Development at 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.”
Neuren Executive Chairman Dr. Richard Treagus commented, “We are delighted to be partnering with ACADIA in North America. ACADIA’s team has a proven record in developing and commercializing medicines in central nervous system disorders with no approved therapies and high unmet needs. ACADIA’s additional capabilities and resources will immediately make a very significant difference, enabling us to advance our shared goal of developing this novel treatment option for Rett syndrome patients.”
Steve Kaminsky, Ph.D., Chief Science Officer of Rettsyndrome.org, commented, “Rettsyndrome.org is grateful to Neuren for their dedication to the development of trofinetide. ACADIA’s commitment to advance trofinetide to Phase 3 brings us closer to the first potential treatment for Rett syndrome with a drug designed to address the underlying biology and improve the lives of those suffering from the condition.”
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 disease1,2. Trofinetide has been granted U.S. Food and Drug Administration (FDA) Fast Track Status and Orphan Drug Designation in the U.S. and Europe.
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 RSBQ and the CGI-I. This followed positive trends observed in an earlier Phase 2 trial in adolescents and adults aged 16 to 45 years with Rett syndrome3. In addition, Neuren has completed an exploratory study in Fragile X syndrome.
Dr. Daniel Glaze, Medical Director at the Blue Bird Circle Rett Center, Texas Children’s Hospital commented, “The trofinetide Phase 2 results in Rett syndrome are very promising in terms of both safety and clinical benefit. For many families, these improvements would provide meaningful improvement in their child’s quality of life.”
Under the terms of the License Agreement, Neuren is eligible to receive US $10 million upfront plus potential milestone payments of up to US $455 million. 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 US $105 million subject to achievement of development milestones in Rett syndrome and Fragile X syndrome and up to US $350 million 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.
About Trofinetide
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 disease1,2. Trofinetide has been granted U.S. FDA Fast
Track Status and Orphan Drug Designation in the U.S. and Europe for both
Rett syndrome and Fragile X syndrome.
About Rett Syndrome
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. Rett syndrome is caused by mutations
on the X chromosome on a gene called MeCP24. There are more
than 200 different mutations found on the MeCP2 gene that interfere with
its ability to generate a normal gene product4. Rett syndrome
occurs worldwide in approximately one of every 10,000 to 15,000 female
births5 causing problems in brain function that are
responsible for cognitive, sensory, emotional, motor and autonomic
function. 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 living5. Symptoms also include seizures,
disorganized breathing patterns, an abnormal side-to-side curvature of
the spine (scoliosis) and sleep disturbances. Currently, there are no
approved medicines approved for the treatment of Rett syndrome1.
About Fragile X syndrome
Fragile X syndrome is the most
common inherited cause of intellectual disability and the most common
known cause of autism. Fragile X syndrome is caused by a single gene
defect on the X chromosome that impacts the FMRP protein, which is
responsible for regulating the synapses of nerve cells. One of every
5,000 males and one of every 4,000 to 8,000 females are estimated to
have the full gene mutation6. Generally males are more
severely affected than females. Clinically, Fragile X syndrome is
characterized by intellectual disability, hyperactivity and attentional
problems, autistic symptoms, anxiety, emotional lability and epilepsy.
Currently, there are no medicines approved for the treatment of Fragile
X syndrome.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical
company focused on the development and commercialization of innovative
medicines to address unmet medical needs in central nervous system
disorders. ACADIA has developed and is commercializing the first and
only medicine approved for the treatment of hallucinations and delusions
associated with Parkinson’s disease psychosis. In addition, ACADIA has
ongoing clinical development efforts in additional areas with
significant unmet need including dementia-related psychosis,
schizophrenia inadequate response, schizophrenia-negative symptoms and
major depressive disorder. This press release and further information
about ACADIA can be found at: www.acadia-pharm.com.
About Neuren Pharmaceuticals
Neuren Pharmaceuticals Limited
(Neuren) is a biopharmaceutical company developing new therapies for
brain injury, neurodevelopmental and neurodegenerative disorders. Neuren
has completed Phase 2 development of trofinetide for Rett syndrome and
has completed a Phase 2 clinical trial in Fragile X syndrome.
About Rettsyndrome.org
Rettsyndrome.org
is one of the leading private funders of Rett syndrome research. The
organization hosts the largest global gathering of Rett researchers and
clinicians to establish research direction for the future. The mission
of the organization is to accelerate the full spectrum research to cure
Rett syndrome and empower families with information, knowledge and
connectivity. Further information about Rettsyndrome.org can
be found at: rettsyndrome.org.
Forward-Looking Statements
Statements in this press release
that are not strictly historical in nature are forward-looking
statements. These statements include but are not limited to statements
regarding the timing of the commencement of the Phase 3 clinical trial
evaluating trofinetide; the likelihood of success of such clinical
trial; the prospects for FDA approval of trofinetide for Rett syndrome
and other indications; and the success of any efforts to commercialize
trofinetide in North America. These statements are only predictions
based on current information and expectations and involve a number of
risks and uncertainties. Actual events or results may differ materially
from those projected in any of such statements due to various factors,
including the risks and uncertainties inherent in drug discovery,
development, approval and commercialization. For a discussion of these
and other factors, please refer to ACADIA’s annual report on Form 10-K
for the year ended December 31, 2017 as well as ACADIA’s subsequent
filings with the Securities and Exchange Commission. You are cautioned
not to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. This caution is made under the safe
harbor provisions of the Private Securities Litigation Reform Act of
1995. All forward-looking statements are qualified in their entirety by
this cautionary statement and ACADIA undertakes no obligation to revise
or update this press release to reflect events or circumstances after
the date hereof, except as required by law.
This ASX-announcement contains forward-looking statements that are subject to risks and uncertainties. Such statements involve known and unknown risks and important factors that may cause the actual results, performance or achievements of Neuren to be materially different from the statements in this announcement.
References
1Tropea, D., et al. (2009). "Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice." Proc Natl Acad Sci U S A 106(6): 2029-2034.
2Vahdatpour, C., et al. (2016). "Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders." Front Neurosci 10: 450.
3Glaze, D. G., et al. (2017). "A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome." Pediatr Neurol 76: 37-46.
4Chahrour, M. and H. Y. Zoghbi (2007). "The story of Rett syndrome: from clinic to neurobiology." Neuron 56(3): 422-437.
5Ip, J. P. K., et al. (2018). "Rett syndrome: insights into genetic, molecular and circuit mechanisms." Nat Rev Neurosci 19(6): 368-382.
6Hagerman, R.J., et al. (2017). “Fragile X syndrome.” Nat Rev Disease Primers 3: 1-19.
