-- Expanded agreement follows Acadia’s April
2023 U.S. launch of DAYBUE™ (trofinetide) as the first and only
drug approved for the treatment of Rett syndrome
-- Acadia provides DAYBUE launch update and
announces second quarter preliminary net sales and guidance for
third quarter
-- Company to host conference call and webcast
today at 4:30 p.m. Eastern Time
Acadia Pharmaceuticals Inc. (NASDAQ: ACAD) today announced that
it has 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, Acadia’s President and Chief
Executive Officer. “We have successfully delivered DAYBUE, the
first FDA-approved therapy that treats the core symptoms of Rett
syndrome, and are deeply committed to broadening access to this
important therapy for patients worldwide.”
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.
Execution of this agreement advances Acadia’s corporate strategy
to expand our rare disease business. This deal also enables Acadia
to leverage insights from our successful U.S. launch of DAYBUE in
other global territories. In addition, this expansion will further
advance the global potential of Acadia’s current development
portfolio.
Acadia intends to submit a New Drug Submission (NDS) for
trofinetide in Canada in the next 18 months with plans for Europe,
Asia and other regions to be announced at a later date.
Financial Terms
Under the terms of the expanded agreement, Neuren will receive
an upfront payment of US $100 million and is eligible to receive
additional potential downstream milestone and royalty payments
earned separately for trofinetide and NNZ-2591.
Outside of North America, Neuren is eligible to receive
additional payments for trofinetide upon the achievement of
specified revenue milestones as follows:
First Commercial Sales Milestones
Total Sales Milestones(1)
Europe
$35M (Rett); $10M (2nd indication)
Up to $170M
Japan
$15M (Rett); $4M (2nd indication)
Up to $110M
Rest of World
-0-
Up to $83M
(1)
Each region’s sales milestones are divided
into four distinct milestones based upon escalating annual net
sales thresholds as defined in the agreement.
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.
Preliminary Second Quarter Revenues and Updated Guidance
DAYBUE
- DAYBUE 2Q 2023 preliminary net sales: $21 to $23 million.
- DAYBUE 3Q 2023 net sales guidance:
$45 to $55 million.
NUPLAZID
- NUPLAZID 2Q 2023 preliminary net sales: $140 to $144
million.
- NUPLAZID Full Year 2023 net sales
guidance: $530 to $545 million.
Conference Call and Webcast Information
Acadia will discuss the exclusive worldwide licensing of
trofinetide and NNZ-2591 via conference call and webcast today at
4:30 p.m. Eastern Time. The conference call will be available on
Acadia’s website, www.acadia.com under the investors section and
will be archived there until August 12, 2023. The conference call
may also be accessed by registering for the call here. Once
registered, participants will receive an email with the dial-in
number and unique PIN number to use for accessing the call.
About Rett Syndrome
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 U.S., with approximately 4,500 patients
currently diagnosed according to an analysis of healthcare claims
data.1-4 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.3 Rett syndrome is typically caused by a
genetic mutation on the MECP2 gene.5 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.5-7
Symptoms of Rett syndrome may also include development of hand
stereotypies, such as hand wringing and clapping, and gait
abnormalities.8 Most Rett patients typically live into adulthood
and require round-the-clock care.2,9
About DAYBUE™ (trofinetide)
Trofinetide is a synthetic version of a naturally occurring
molecule known as the tripeptide glycine-proline-glutamate (GPE).
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.10,11
Important Safety Information for DAYBUE™
(trofinetide)
- Warnings and Precautions
- Diarrhea: In a 12-week study and in long-term studies,
an aggregate of 85% of patients treated with DAYBUE experienced
diarrhea. In those treated with DAYBUE, 49% either had persistent
diarrhea or recurrence after resolution despite dose interruptions,
reductions, or concomitant antidiarrheal therapy. Diarrhea severity
was of mild or moderate severity in 96% of cases. In the 12-week
study, antidiarrheal medication was used in 51% of patients treated
with DAYBUE. Patients should stop taking laxatives before starting
DAYBUE. If diarrhea occurs, patients should notify their healthcare
provider, consider starting antidiarrheal treatment, and monitor
hydration status and increase oral fluids, if needed. Interrupt,
reduce dose, or discontinue DAYBUE if severe diarrhea occurs or if
dehydration is suspected.
- Weight Loss: In the 12-week study, 12% of patients
treated with DAYBUE experienced weight loss of greater than 7% from
baseline, compared to 4% of patients who received placebo. In
long-term studies, 2.2% of patients discontinued treatment with
DAYBUE due to weight loss. Monitor weight and interrupt, reduce
dose, or discontinue DAYBUE if significant weight loss occurs.
- Adverse Reactions: The common adverse reactions (≥5% for
DAYBUE-treated patients and at least 2% greater than in placebo)
reported in the 12-week study were diarrhea (82% vs 20%), vomiting
(29% vs 12%), fever (9% vs 4%), seizure (9% vs 6%), anxiety (8% vs
1%), decreased appetite (8% vs 2%), fatigue (8% vs 2%), and
nasopharyngitis (5% vs 1%).
- Drug Interactions: Effect of DAYBUE on other Drugs
- DAYBUE is a weak CYP3A4 inhibitor; therefore, plasma
concentrations of CYP3A4 substrates may be increased if given
concomitantly with DAYBUE. Closely monitor when DAYBUE is used in
combination with orally administered CYP3A4 sensitive substrates
for which a small change in substrate plasma concentration may lead
to serious toxicities.
- Plasma concentrations of OATP1B1 and OATP1B3 substrates may be
increased if given concomitantly with DAYBUE. Avoid the concomitant
use of DAYBUE with OATP1B1 and OATP1B3 substrates for which a small
change in substrate plasma concentration may lead to serious
toxicities.
- Use in Specific Population: Renal Impairment
- DAYBUE is not recommended for patients with moderate or severe
renal impairment.
DAYBUE is available as an oral solution (200 mg/mL).
Please read the accompanying full Prescribing
Information, also available at
DAYBUE.com
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 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% 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.12,13
Currently, there are no medicines approved for the treatment of
Fragile X syndrome.
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate
life. For 30 years we have been working at the forefront of
healthcare to bring vital solutions to people who need them most.
We developed and commercialized the first and only approved
therapies for hallucinations and delusions associated with
Parkinson’s disease psychosis and for the treatment of Rett
syndrome. Our clinical-stage development efforts are focused on
treating the negative symptoms of schizophrenia, Prader-Willi
syndrome, Alzheimer’s disease psychosis and neuropsychiatric
symptoms in central nervous system disorders. For more information,
visit us at www.acadia.com and follow us on LinkedIn and
Twitter.
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 future events. 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 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, 2022, 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.
References
1Acadia Pharmaceuticals Inc, Data on file. RTT US Prevalence.
March 2022. 2Fu C, Armstrong D, Marsh E, et al. Consensus
guidelines on managing Rett syndrome across the lifespan. BMJ
Paediatrics Open. 2020; 4: 1-14. 3Kyle SM, Vashi N, Justice MJ.
Rett syndrome: a neurological disorder with metabolic components.
Open Biol. 2018; 8: 170216. 4Acadia Pharmaceuticals Inc, Data on
file. 5Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is
caused by mutations in X-linked MECP2, encoding methyl-CpG-binding
protein 2. Nat Genet. 1999; 23(2): 185-188. 6Fukuda T, Itoh M,
Ichikawa T, et al. Delayed maturation of neuronal architecture and
synaptogenesis in cerebral cortex of Mecp2-deficient mice. J
Neuropathol Exp Neurol. 2005; 64(6): 537-544. 7Asaka Y, Jugloff DG,
Zhang L, et al. Hippocampal synaptic plasticity is impaired in the
Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2006;
21(1): 217-227. 8Neul JL, Kaufmann WE, Glaze DG, et al. Rett
syndrome: revised diagnostic criteria and nomenclature. Ann Neurol.
2010; 68(6): 944-950. 9Daniel C, Tarquinio DO, Hou W, et al. The
changing face of survival in Rett syndrome and MECP2-related
disorders. Pediatr Neurol. 2015; 53(5): 402-411. 10Tropea D,
Giacometti E, Wilson NR, et al. Partial reversal of Rett
Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci
USA. 2009; 106(6): 2029-2034. 11Acadia Pharmaceuticals Inc, Data on
file. Study Report 2566-026. 2010. 12Neuren Pharmaceuticals.
Fragile X Syndrome. Retrieved from
https://www.neurenpharma.com/products/trofinetide/fragile-x-syndrome.
Accessed July 13, 2023. 13UpToDate. Fragile X syndrome: Clinical
features and diagnosis in children and adolescents. Retrieved from
https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents#H3365848815.
Accessed July 13, 2023.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230713748693/en/
Media Contact: Acadia Pharmaceuticals Inc. Deb Kazenelson (818)
395-3043 media@acadia-pharm.com
Investor Contact: Acadia Pharmaceuticals Inc. Jessica Tieszen
(858) 261-2950 ir@acadia-pharm.com
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