Trofinetide

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the journal Med published results from the open-label study, DAFFODIL™, evaluating the safety, tolerability and exploratory efficacy of DAYBUE® (trofinetide) in girls ages two to four living with Rett syndrome (n = 15). The long-term Phase 2/3 study demonstrated DAYBUE had a similar safety profile in children two to four years of age as that observed in individuals with Rett syndrome five years of age and older in the 12-week LAVENDER™ study, and the 40-week LILAC-1™ and 32-month LILAC-2™ open-label extension studies. Results of all four studies supported the FDA approval of DAYBUE in adults and pediatric patients two years of age or older. “Rett syndrome is a debilitating condition that often causes patients to lose acquired communication and motor skills starting as early as six to 18 months old which presents significant challenges for these children and their families,” said Alan Percy, M.D., Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at University of Alabama, Birmingham and lead DAFFODIL author. “Outcomes from DAFFODIL further underscore trofinetide’s safety and tolerability across patient age groups and provide additional data to inform treatment plans and dosing for patients closer to the onset of symptoms.” “The final DAFFODIL results provide critical insights into the safety and tolerability of DAYBUE in younger pediatric Rett syndrome patients, including effective strategies to mitigate common side effects of treatment,” said Ponni Subbiah, M.D., M.P.H., Acadia’s Senior Vice President, Global Head of Medical Affairs and Chief Medical Officer. “These findings, along with the caregiver exit interview feedback from the study, further our understanding of trofinetide’s role in managing this complex condition and the potential benefits of longer-term treatment.” Diarrhea (80.0%) and vomiting (53.3%) were the most common treatment emergent adverse events (TEAEs), and all cases were of mild or moderate severity. Two participants discontinued the study early due to adverse events. The use of a diarrhea management plan, including discontinuation of laxatives and initiation of fiber, led to only one discontinuation due to diarrhea over the 78-week study. Serious TEAEs (n = 4) were considered unrelated to treatment. The following exploratory efficacy endpoints supported symptom improvement: Clinical Global Impression–Improvement (CGI-I) scale score (7-point scale where 1 is “very much improved” and 7 is “very much worse”) was 3.3 ± 0.19 (mean ± standard error) at Week 4 and continued to improve to 2.2 ± 0.22 at Week 78. Caregiver Global Impression–Improvement (CaGI-I) scale score (5-point scale where 1 is “much improved” and 5 is “much worse”) at Week 12 (2.3 ± 0.12) and Week 78 (2.1 ± 0.31) indicated improvement compared with baseline. Impact of Childhood Neurologic Disability-Quality of Life (ICND-QoL) scale (6-point scale where 1 is “poor” and 6 is “excellent”) increased from baseline to Week 78 (3.9 ± 0.24 to 4.6 ± 0.31). Caregivers (n = 7) who participated in the study exit interviews most frequently identified inability to communicate as the most impactful symptom of Rett syndrome (42.9%) and improved communication as the most desired treatment effect (71.4%). The most frequently reported improvements by caregivers during the exit interviews were in verbal communication (ability to say new words) (71.4%), improved eye contact (57.1%) and improved hand use (57.1%). 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) 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 Important Safety Information for DAYBUE® (trofinetide) 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. 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. 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 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 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%). 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. DAYBUE is not recommended for patients with 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 Acadia Pharmaceuticals Acadia is advancing breakthroughs in neuroscience to elevate life. Since our founding 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 FDA-approved drug to treat hallucinations and delusions associated with Parkinson’s disease psychosis and the first and only approved drug in the United States and Canada for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on Prader-Willi syndrome, Alzheimer’s disease psychosis and multiple other programs targeting neuro-psychiatric and neuro-rare diseases. For more information, visit us at Acadia.com and follow us on LinkedIn and X. References 1 Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020; 4:1-14. 2 Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018; 8: 170216. 3 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. 4 Acadia Pharmaceuticals Inc, Data on file. RTT US Prevalence. March 2022. 5 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. 6 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. 7 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. 8 Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68(6): 944-950. 9 Tarquinio DC, Hou W, JL Neul et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015; 53(5): 402-411. 10 Acadia Pharmaceuticals Inc., Data on file. Study Report 2566-026. 2010.

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced its financial results for the fourth quarter and full year ended December 31, 2024. “We closed 2024 on a strong note with each of our brands achieving record revenues in the fourth quarter and well-positioned for continued growth in 2025,” said Catherine Owen Adams, Chief Executive Officer. “To support this growth in 2025 we will continue investing in consumer activation to drive market share expansion for NUPLAZID in the US. We plan to expand our DAYBUE field force in the US and build our EU commercial team in anticipation of potentially launching trofinetide there next year. Beyond the growth of our commercial brands, our later-stage pipeline programs are advancing toward key milestones, including topline readouts starting in the first half of 2026, and our ongoing business development efforts continue to produce compelling opportunities like ACP-711 and other programs that we are excited to share more about at our inaugural R&D Day in June.” Company Updates In January, the marketing authorization application for trofinetide was submitted to the European Medicines Agency (EMA) with expected approval in the first quarter of 2026. In January, the Company provided timeline updates for its two most advanced clinical development programs: For the COMPASS PWS Phase 3 study of ACP-101 in Prader-Willi Syndrome, the last patient is expected to be enrolled in the fourth quarter of 2025, followed by the announcement of topline results in the first half of 2026. For the RADIANT Phase 2 study of ACP-204 in Alzheimer’s disease psychosis, the last patient is expected to be enrolled in the first quarter of 2026, followed by the announcement of topline results in mid-2026. For the COMPASS PWS Phase 3 study of ACP-101 in Prader-Willi Syndrome, the last patient is expected to be enrolled in the fourth quarter of 2025, followed by the announcement of topline results in the first half of 2026. For the RADIANT Phase 2 study of ACP-204 in Alzheimer’s disease psychosis, the last patient is expected to be enrolled in the first quarter of 2026, followed by the announcement of topline results in mid-2026. In January, the Company announced plans for the initiation of a Phase 2 study of ACP-204 for a second indication in Lewy Body Dementia Psychosis in the third quarter of 2025. In December 2024, the Company announced the closing of the sale of its Rare Pediatric Disease Priority Review Voucher (PRV) for $150 million before fees and expenses. In December 2024, the Company announced the appointment of Thomas Andrew Garner as Chief Commercial Officer. In November 2024, the Company announced an exclusive worldwide license agreement with Saniona for the development and commercialization of ACP-711, a potential first-in-class, highly selective GABA A -α3 positive allosteric modulator and plans to initiate a Phase 2 study in essential tremor in 2026. Financial Results Revenues Total revenues comprising of net product sales from NUPLAZID and DAYBUE were $259.6 million for the fourth quarter of 2024 and $957.8 million for the full year 2024. Net product sales of NUPLAZID were $162.9 million for the fourth quarter of 2024, an increase of 13% as compared to $143.9 million for the fourth quarter of 2023. Net product sales of NUPLAZID were $609.4 million for the full year 2024, an increase of 11% as compared to $549.2 million for the full year 2023. The increase in net product sales of NUPLAZID was due to growth in unit sales and a higher average net selling price in 2024 compared to 2023. Net product sales of DAYBUE were $96.7 million for the fourth quarter of 2024, an increase of 11% as compared to $87.1 million for the fourth quarter of 2023. Net product sales of DAYBUE were $348.4 million for the full year 2024, an increase of 97% as compared to $177.2 million for the full year 2023. The increase in net product sales of DAYBUE was mainly due to the growth in unit sales in 2024 compared to 2023. Research and Development Research and development expenses for the fourth quarter of 2024 were $100.7 million, compared to $66.7 million for the same period of 2023. For the full years of 2024 and 2023, research and development expenses were $303.2 million and $351.6 million, respectively. The decrease in research and development expenses during 2024 was due to decreased business development payments, which in the period ending December 31, 2023, included the $100.0 million payment to Neuren Pharmaceuticals Limited under the expanded license agreement for trofinetide, partially offset by increased costs from clinical stage programs. Selling, General and Administrative Selling, general and administrative expenses for the fourth quarter of 2024 were $130.1 million, compared to $111.5 million for the same period of 2023. For the full years of 2024 and 2023, selling, general and administrative expenses were $488.4 million and $406.6 million, respectively. The increase in selling, general and administrative expenses was primarily driven by increased marketing costs to support the NUPLAZID and DAYBUE franchises in the U.S. and investments to support commercialization of trofinetide outside the U.S. Net Income (Loss) For the fourth quarter of 2024, Acadia reported net income of $143.7 million, or $0.86 per common share, compared to a net income of $45.8 million, or $0.28 per common share, for the same period in 2023. Net income for the fourth quarters of 2024 and 2023 included $10.5 million and $18.0 million, respectively, of non-cash stock-based compensation expense. For the full year 2024, Acadia reported a net income of $226.5 million, or $1.37 per common share, compared to a net loss of $61.3 million, or $0.37 per common share, for the same period in 2023. Net income in the fourth quarter and for the full year of 2024 included a one-time gain on sale of a non-financial asset as we sold the PRV to a third party for the aggregate net proceeds of $146.5 million. The net income and loss for the full years of 2024 and 2023 included $67.0 million and $66.4 million, respectively, of non-cash stock-based compensation expense. Cash and Investments At December 31, 2024, Acadia’s cash, cash equivalents, and investment securities totaled $756.0 million, compared to $438.9 million at December 31, 2023. Full Year 2025 Financial Guidance Total Revenues (U.S. only) of $1.03 to $1.095 billion NUPLAZID net product sales in the range of $650 to $690 million. DAYBUE net product sales (U.S. only) in the range of $380 to $405 million R&D expense in the range of $310 to $330 million SG&A expense in the range of $535 to $565 million Conference Call and Webcast Information Acadia will host a conference call to discuss the fourth quarter and full year December 31, 2024 results today, Wednesday, February 26, 2025 at 1:30 p.m. PT/4:30 p.m. ET. The conference call may 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 NUPLAZID® (pimavanserin) Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID. 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. Trofinetide was approved for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older by the U.S. Food and Drug Administration in March 2023 under the trade name DAYBUE. About Acadia Pharmaceuticals Acadia is advancing breakthroughs in neuroscience to elevate life. Since our founding 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 FDA-approved drug to treat hallucinations and delusions associated with Parkinson’s disease psychosis and the first and only approved drug in the United States and Canada for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on Prader-Willi syndrome, Alzheimer’s disease psychosis and multiple other programs targeting neuroscience and neuro-rare diseases. 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,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential,” “continue” 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) our business strategy, objectives and opportunities, including support for and innovations in our pipeline assets and business development opportunities, investments in consumer activation, expansion of our DAYBUE sales force in the US, and building of our EU commercial team, and potential for enhanced shareholder value; (ii) plans for, including timing, development and progress of commercialization or regulatory timelines for our products, including NUPLAZID and DAYBUE, and our product candidates; (iii) benefits to be derived from and efficacy of our products, including the potential advantages of our products; (iv) the timing and conduct of our clinical trials, including continued enrollment of our clinical trials in Prader-Willi syndrome and Alzheimer’s disease psychosis, the initiation of our clinical trial in Lewy Body Dementia Psychosis, and the timing and content of our presentations or announcements regarding our clinical trials; (v) our estimates regarding our future financial performance, profitability or capital requirements, including our full year 2025 financial guidance, and (vi) our ability to successfully complete additional business development transactions. 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 and other factors include, but are not limited to: our dependency on the continued successful commercialization of our products and our ability to maintain or increase sales of our products; our plans to commercialize DAYBUE in Canada and trofinetide in the EU; the costs of our commercialization plans and development programs, and the financial impact or revenues from any commercialization we undertake; our ability to obtain necessary regulatory approvals for our product candidates and, if and when approved, market acceptance of our products; the risks associated with clinical trials and their outcomes, including risks of unsuccessful enrollment and negative or inconsistent results; our dependence on third-party collaborators, clinical research organizations, manufacturers, suppliers and distributors; the impact of competitive products and therapies; our ability to generate or obtain the necessary capital to fund our operations; our ability to grow, equip and train our specialized sales forces; our ability to manage the growth and complexity of our organization; our ability to maintain, protect and enhance our intellectual property; 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 and other factors that may cause our actual results, performance or achievements to differ, please refer to our quarterly report on Form 10-Q for the quarter ended September 30, 2024, filed on November 7, 2024, as well as our subsequent filings with the Securities and Exchange Commission from time to time. 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. ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except per share amounts) (Unaudited) Three Months Ended December 31, Years Ended December 31, 2024 2023 2024 2023 Revenues Product sales, net $ 259,602 $ 231,041 $ 957,797 $ 726,437 Total revenues 259,602 231,041 957,797 726,437 Operating expenses Cost of product sales (1)(2) 21,803 17,891 81,841 41,638 Research and development (2) 100,731 66,741 303,249 351,619 Selling, general and administrative (2) 130,080 111,465 488,428 406,559 Gain on sale of non-financial asset (146,515 ) — (146,515 ) — Total operating expenses 106,099 196,097 727,003 799,816 Income (loss) from operations 153,503 34,944 230,794 (73,379 ) Interest income, net 7,007 4,759 25,458 17,234 Other income 575 — 1,823 5,109 Income (loss) before income taxes 161,085 39,703 258,075 (51,036 ) Income tax expense (benefit) 17,343 (6,094 ) 31,624 10,250 Net income (loss) $ 143,742 $ 45,797 $ 226,451 $ (61,286 ) Earnings (net loss) per share: Basic $ 0.86 $ 0.28 $ 1.37 $ (0.37 ) Diluted $ 0.86 $ 0.28 $ 1.36 $ (0.37 ) Weighted average common shares outstanding: Basic 166,535 164,812 165,717 163,819 Diluted 166,696 166,510 166,362 163,819 (1) Includes license fees and royalties (2) Includes the following share-based compensation expenses Cost of product sales, license fees and royalties $ 421 $ 363 $ 1,319 $ 1,007 Research and development $ 2,395 $ 4,707 $ 14,100 $ 17,408 Selling, general and administrative $ 7,634 $ 12,953 $ 51,630 $ 48,006 ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) (Unaudited) December 31, 2024 December 31, 2023 Assets Cash, cash equivalents and investment securities $ 755,993 $ 438,865 Accounts receivable, net 98,739 98,267 Interest and other receivables 5,956 4,083 Inventory 21,949 35,819 Prepaid expenses 55,681 39,091 Total current assets 938,318 616,125 Property and equipment, net 4,215 4,612 Operating lease right-of-use assets 46,571 51,855 Intangible assets, net 119,782 65,490 Restricted cash 8,770 5,770 Long-term inventory 69,741 4,628 Other assets 359 476 Total assets $ 1,187,756 $ 748,956 Liabilities and stockholders’ equity Accounts payable $ 16,192 $ 17,543 Accrued liabilities 378,678 236,711 Total current liabilities 394,870 254,254 Operating lease liabilities 42,037 47,800 Other long-term liabilities 18,056 15,147 Total liabilities 454,963 317,201 Total stockholders’ equity 732,793 431,755 Total liabilities and stockholders’ equity $ 1,187,756 $ 748,956