Trofinetide

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the U.S. Food and Drug Administration (FDA) has approved DAYBUE® STIX (trofinetide) for oral solution, a dye- and preservative-free powder formulation of trofinetide for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. The new formulation is expected to deliver the same efficacy and safety profile of DAYBUE oral solution, while offering children and adults living with Rett syndrome new flexibility and choice regarding the dose volume and taste of their DAYBUE treatment. “DAYBUE, the first and only approved treatment for Rett syndrome, has provided thousands of patients an important therapeutic option,” said Catherine Owen Adams, Acadia’s Chief Executive Officer. “With the approval of DAYBUE STIX, we are building on our commitment to turn scientific promise into meaningful innovation by introducing a new formulation informed by invaluable feedback from patients, caregivers and healthcare providers.” “The new formulation gives us an additional option for treatment with DAYBUE, allowing us to better customize care for our patients,” said Jennifer Martelle Tu, M.D., Ph.D., Director of Katie's Clinic for Rett Syndrome and Associate Professor of Neurology, UCSF Benioff Children's Hospitals, Oakland. “DAYBUE STIX is a powder for oral solution that caregivers can mix with a variety of water-based liquids providing flexibility to modify the taste and volume of their loved-one's dose. We know that this kind of adaptability is something many Rett families have been seeking.” The efficacy and safety of DAYBUE STIX is based on the results of the LAVENDER™ study with DAYBUE oral solution in patients with Rett syndrome. The approval of this new formulation was informed by the results of a bioequivalence study, which demonstrated that both original DAYBUE oral solution and the new DAYBUE STIX for oral solution powder formulation provide comparable exposure. This confirmed bioequivalence means patients can expect the same efficacy and safety established by the oral solution formulation when using DAYBUE STIX. DAYBUE STIX will be available on a limited basis starting in the first quarter of 2026 and more broadly early in the second quarter of 2026. The current oral solution formulation will remain available. About Rett Syndrome Rett syndrome is a rare, complex, neurodevelopmental disorder that may occur over four stages and occurs in approximately one of every 10,000 to 15,000 female births worldwide.1-3 In the U.S., 6,000 to 9,000 patients are affected.4 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.2 Rett syndrome is typically caused by a genetic mutation on the MECP2 gene.5 In preclinical studies, deficiency in MeCP2 function is thought 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.1,9 About DAYBUE® (trofinetide) and DAYBUE® STIX (trofinetide) Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1. 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 Indication and Important Safety Information for DAYBUE® (trofinetide) and DAYBUE® STIX (trofinetide) Indication DAYBUE and DAYBUE STIX are indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older. Important Safety Information Diarrhea: In a 12-week study and in long-term studies, 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 mild or moderate in 96% of cases. In the 12-week study, antidiarrheal medication was used in 51% of patients treated with DAYBUE. Advise patients to stop laxatives before starting DAYBUE or DAYBUE STIX. 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 or DAYBUE STIX if severe diarrhea occurs or if dehydration is suspected. Vomiting: In a 12-week study, vomiting occurred in 29% of patients treated with DAYBUE and in 12% of patients who received placebo . Patients with Rett syndrome are at risk for aspiration and aspiration pneumonia. Aspiration and aspiration pneumonia have been reported following vomiting in patients being treated with DAYBUE. Interrupt, reduce dose, or discontinue DAYBUE or DAYBUE STIX if vomiting is severe or occurs despite medical management. 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 or DAYBUE STIX 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%). Trofinetide, a weak inhibitor of CYP3A and an inhibitor of P-gp, can increase the plasma concentrations of CYP3A and/or P-gp substrates (e.g., loperamide), which may increase the risk of adverse reactions associated with these substrates . Closely monitor patients when DAYBUE or DAYBUE STIX is administered concomitantly with sensitive CYP3A and/or P-gp substrates for which a minimal increase in substrate plasma concentration (i.e., drugs with a narrow therapeutic index) may lead to serious adverse reactions. DAYBUE and DAYBUE STIX are not recommended for patients with severe renal impairment. DAYBUE is available as an oral solution (200 mg/mL). DAYBUE STIX for oral solution powder is available in 5,000 mg, 6,000 mg, and 8,000 mg packets. Please read the full Prescribing Information also available at DAYBUEhcp.com. About Acadia Pharmaceuticals Acadia is committed to turning scientific promise into meaningful innovation that makes the difference for underserved neurological and rare disease communities around the world. Our commercial portfolio includes the first and only FDA-approved treatments for Parkinson’s disease psychosis and Rett syndrome. We are developing the next wave of therapeutic advancements with a robust and diverse pipeline that includes mid- to late-stage programs in Alzheimer’s disease psychosis and Lewy body dementia psychosis, along with earlier-stage programs that address other underserved patient needs. At Acadia, we’re here to be their difference. For more information, visit us at acadia.com and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “expects,” “anticipates,” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release, include, but are not limited to, statements about: (i) the efficacy and safety profile of DAYBUE and DAYBUE STIX and anticipated Rett syndrome symptom improvements, and (ii) the flexibility in administration provided by DAYBUE STIX. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties, assumptions and other factors include, but are not limited to: our ability to continue to successfully commercialize DAYBUE and DAYBUE STIX and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ, please refer to our annual report on Form 10-K for the year ended December 31, 2024 filed with the Securities and Exchange Commission on February 26, 2025, as well as our subsequent filings with the Securities and Exchange Commission from time to time, including our quarterly report on Form 10-Q for the quarter ended September 30, 2025. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law. References Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open . 2020; 4:1-14. Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol . 2018; 8:170216. May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J of Med Econ . 26(1), 1570–1580. Acadia Pharmaceuticals Inc, Data on file. RTT US Prevalence. March 2022. Amir 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. Fukuda 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. Asaka 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. Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol . 2010; 68(6):944-950. Tarquinio DO, Hou W, Neul JL, et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol . 2015; 53(5):402-411. Acadia Pharmaceuticals Inc., Data on file. Study Report 2566-026. 2010.