5-HT1A receptor agonists(Serotonin 1a (5-HT1a) receptor agonists), 5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), D2 receptor agonists(Dopamine D2 receptor agonists)

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Depressive DisorderAgitation in DementiaAgitation+ [8]

Inactive Indication

Anxiety DisordersAttention Deficit and Disruptive Behavior DisordersAttention Deficit Disorder With Hyperactivity+ [9]

Originator Organization

Otsuka Pharmaceutical Co., Ltd.

Active Organization

Otsuka Pharmaceutical Co., Ltd.

Zhejiang Heze Pharmaceutical Technology Co., Ltd.Otsuka Holdings Co., Ltd.

+ [19]

Inactive Organization

Otsuka Beijing Research Institute

Drug Highest PhaseApproved

First Approval Date

US (10 Jul 2015),

Depressive Disorder, MajorSchizophrenia

RegulationPriority Review (US), Fast Track (US)

Structure

Molecular FormulaC25H27N3O2S

InChIKeyZKIAIYBUSXZPLP-UHFFFAOYSA-N

CAS Registry913611-97-9

194

Clinical Trials associated with Brexpiprazole

CTR20244158 / RecruitingNot Applicable

布瑞哌唑口溶膜在中国健康受试者中进行的单中心、随机、开放、单次口服给药、两制剂、三序列、三周期（空腹）/两序列、两周期（餐后）、交叉的人体生物等效性试验

[Translation] A single-center, randomized, open-label, single oral administration, two-formulation, three-sequence, three-cycle (fasting)/two-sequence, two-cycle (fed), crossover human bioequivalence study of brexpiprazole orodispersible film in healthy Chinese subjects

主要目的：观察中国健康受试者在空腹/餐后状态下单次口服受试制剂布瑞哌唑口溶膜（规格：2mg；生产企业：海南葫芦娃药业集团股份有限公司）和参比制剂布瑞哌唑片（商品名：Rexulti®；规格：2mg；持证商：Otsuka Pharmaceutical Co Ltd）后的药代动力学特征，评价空腹/餐后状态下两种制剂的生物等效性。次要目的：观察受试制剂布瑞哌唑口溶膜和参比制剂布瑞哌唑片（Rexulti®）在中国健康受试者中的安全性。

[Translation]

Primary objective: To observe the pharmacokinetic characteristics of the test preparation brexpiprazole orodispersible film (specification: 2 mg; manufacturer: Hainan Huluwa Pharmaceutical Group Co., Ltd.) and the reference preparation brexpiprazole tablets (trade name: Rexulti®; specification: 2 mg; licensee: Otsuka Pharmaceutical Co Ltd) in Chinese healthy subjects after a single oral administration in the fasting/fed state, and to evaluate the bioequivalence of the two preparations in the fasting/fed state. Secondary objective: To observe the safety of the test preparation brexpiprazole orodispersible film and the reference preparation brexpiprazole tablets (Rexulti®) in Chinese healthy subjects.

Start Date16 Nov 2024

Sponsor / Collaborator

Hainan Zhongwang Medical Technology Development Co., Ltd.

CTR20243767 / RecruitingNot Applicable

布瑞哌唑片人体生物等效性研究

[Translation] Study on the bioequivalence of breprazol tablets in healthy volunteers

主要研究目的：研究健康受试者在空腹和餐后状态下单次口服受试制剂布瑞哌唑片（规格：2mg，宜昌人福药业有限责任公司生产）与参比制剂布瑞哌唑片（商品名：Rexulti，规格：2mg；持证商：Otsuka Pharmaceutical Co Ltd）后体内的药代动力学，评价空腹和餐后状态口服两制剂的生物等效性。次要研究目的：研究受试制剂布瑞哌唑片2mg和参比制剂布瑞哌唑片（商品名：Rexulti）2mg在健康受试者中的安全性。

[Translation]

The main purpose of the study is to study the pharmacokinetics of the test preparation brepirazole tablets (specification: 2 mg, produced by Yichang Renfu Pharmaceutical Co., Ltd.) and the reference preparation brepirazole tablets (trade name: Rexulti, specification: 2 mg; licensee: Otsuka Pharmaceutical Co Ltd) in healthy subjects after a single oral administration in the fasting and fed state, and to evaluate the bioequivalence of the two preparations in the fasting and fed state. Secondary purpose of the study: to study the safety of the test preparation brepirazole tablets 2 mg and the reference preparation brepirazole tablets (trade name: Rexulti) 2 mg in healthy subjects.

Start Date13 Nov 2024

Sponsor / Collaborator

Yichang Humanwell Pharmaceuticals Co., Ltd.

CTR20243953 / RecruitingNot Applicable

布瑞哌唑片人体生物等效性研究

[Translation] Study on the bioequivalence of brepirazole tablets in healthy volunteers

本试验旨在研究单次空腹和餐后口服上海复旦复华药业有限公司研制、生产的布瑞哌唑片（2 mg）的药代动力学特征；以Otsuka Pharmaceutical Co., Ltd.生产的布瑞哌唑片（Rexulti®，2 mg）为参比制剂，比较两制剂中药动学参数Cmax、AUC0-72，评价两制剂的人体生物等效性。

[Translation]

This study aimed to investigate the pharmacokinetic characteristics of brepirazole tablets (2 mg) developed and produced by Shanghai Fudan Fuhua Pharmaceutical Co., Ltd. after single oral administration on an empty stomach or after a meal. Using brepirazole tablets (Rexulti®, 2 mg) produced by Otsuka Pharmaceutical Co., Ltd. as the reference preparation, the pharmacokinetic parameters Cmax and AUC0-72 of the two preparations were compared, and the bioequivalence of the two preparations in humans was evaluated.

Start Date07 Nov 2024

Sponsor / Collaborator

Shanghai Fudan Forward Pharmaceutical Co. Ltd.

100 Clinical Results associated with Brexpiprazole

100 Translational Medicine associated with Brexpiprazole

100 Patents (Medical) associated with Brexpiprazole

386

Literatures (Medical) associated with Brexpiprazole

01 Dec 2024·Neuropsychopharmacology reports

Correction to “Brexpiprazole: A new option in treating agitation in Alzheimer's dementia‐Insights from transgenic mouse models”

01 Dec 2024·CNS DRUGS

A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder

Article

Author: Shiomi, Yuki ; Kato, Masaki ; Saito, Mizuki ; Sekine, Daisuke ; Aoki, Kazuo ; Iba, Katsuhiro ; Kuwahara, Kazuo ; Shimada, Yuki ; Shiosakai, Masako ; Higuchi, Teruhiko

BACKGROUND AND OBJECTIVE:

Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD.

METHODS:

An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score.

RESULTS:

In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment.

CONCLUSIONS:

This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks.

STUDY REGISTRATION:

ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).

01 Dec 2024·Neuropsychopharmacology reports

Correction to “Synergistic anti‐depressive effect of combination treatment of Brexpiprazole and selective serotonin reuptake inhibitors on forced swimming test in mice”

AmadaN, HiroseT, SuzukiM, KakumotoY, FutamuraT, MaedaK, et al. . Neuropsychopharmacol Rep.2023;43:132–136.In the ‘Methods’ section of the Abstract, the second sentence is as follows:“Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing.”The amount listed for escitalopram is incorrect. It should be: 60 mg/kg.We apologize for this error.

News (Medical) associated with Brexpiprazole

19 Dec 2024

·www.otsuka.co.jp

JAMA Psychiatry Publishes Results of Otsuka and Lundbeck's Phase 3 Trial of Brexpiprazole in Combination with Sertraline in Treatment of Post-Traumatic Stress Disorder (PTSD) in Adults

RSS Brexpiprazole in combination with sertraline demonstrated a statistically significant reduction in overall PTSD symptoms compared to sertraline plus placebo, as measured by change in CAPS-5 total score from Week 1 to Week 101 The safety profile of brexpiprazole in combination with sertraline was consistent with that of brexpiprazole in approved indications1 Otsuka and Lundbeck submitted an sNDA for brexpiprazole in combination with sertraline for the treatment of adults with PTSD in April 2024. The sNDA is currently under FDA review with a PDUFA target date of February 8, 2025 PTSD is a highly prevalent, trauma-based neuropsychiatric disorder that impacts approximately 13 million U.S. adults in a given year, and nearly 6 in 100 people will be diagnosed with PTSD in their lifetime2-6 Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that its US subsidiary Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Lundbeck Pharmaceuticals LLC (Lundbeck) today announced that the full results of a Phase 3 trial of brexpiprazole in combination with sertraline for the treatment of PTSD in adults have been published in JAMA Psychiatry. The results showed that in adults with PTSD, treatment with brexpiprazole in combination with sertraline resulted in statistically significant greater improvement of PTSD symptoms vs treatment with sertraline plus placebo, as measured by change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from Week 1 to Week 10.1 "About 6% of the United States population will have PTSD at some point in their lives, but around only half will seek treatment," said Lori Davis, M.D., clinical professor of psychiatry in the Department of Psychiatry and Behavioral Neurobiology, University of Alabama School of Medicine, who served as lead author on the JAMA Psychiatry manuscript. "The Phase 3 results are an important and encouraging step forward in the hopes of providing PTSD patients with a new therapeutic option in the future." About the Phase 3 Trial The Phase 3 randomized, double-blind, active-controlled, parallel-arm trial (NCT04124614) evaluated the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline for the treatment of PTSD. The trial included 416 adult outpatients who were randomized to receive either brexpiprazole (2-3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with a placebo. The primary endpoint was the change in CAPS-5 total score from randomization (Week 1) to Week 10. Patients receiving brexpiprazole with sertraline showed a statistically significant greater improvement in CAPS-5 total score (-19.2) compared to those receiving sertraline with placebo (-13.6), with a least squares (LS) mean difference of -5.59 (95% CI: -8.79 to -2.38; P<.001). Additionally, both secondary endpoints, the change in the Clinical Global Impression- Severity of Illness score (CGI-S) randomization (week 1) to week 10 and the change in the Brief Inventory of Psychosocial Function (B-IPF) from baseline (Day 0) to week 12, were also met.1 "The clinical trial results demonstrate the potential of brexpiprazole in combination with sertraline as a treatment option for patients with PTSD, a condition that affects millions within the United States," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "The combination of brexpiprazole and sertraline demonstrated meaningful improvements in PTSD symptoms." The safety profile of brexpiprazole in combination with sertraline was consistent with that of brexpiprazole in approved indications. The proportion of treated participants who discontinued due to adverse events was 3.9% (8/205) for brexpiprazole + sertraline and 10.2% (20/196) for sertraline + placebo.1 The adverse events occurring in >=5% for brexpiprazole in combination with sertraline (n=205) compared to sertraline and placebo (n=196) were nausea (12.2% vs 11.7%), fatigue (6.8% vs 4.1%), weight increase (5.9% vs 1.5%), and somnolence (5.4% vs. 2.6%), respectively.1 "The outcome of this trial provides us with an opportunity to help patients with PTSD," said Johan Luthman, executive vice president and head of Research & Development at Lundbeck. "With these promising results, we are committed to working closely with the FDA to help bring brexpiprazole in combination with sertraline to the healthcare professionals serving the PTSD patient community." About CAPS-5 The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a structured interview designed to assess PTSD diagnostic status and symptom severity as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The CAPS-5 consists of 30 items, with a higher score indicating a worse outcome.1 The CAPS-5 includes 20 DSM-5 PTSD-symptom items that are each scored from 0 (absent) to 4 (extreme/incapacitating). The total score is calculated by summing the 20 items, and symptom cluster scores by summing specific items: Intrusion (items 1-5); Avoidance (items 6-7); Negative cognitions and mood (items 8-14); and Arousal and reactivity (items 15-20).1 The CGI-S is a 7-point categorical scale, originally developed for mental disorders, but now applied to various illnesses, that requires a clinician to rate the severity of a patient's illness at the time of assessment, relative to the clinician's experience with patients who have the same diagnosis.7 The B-IPF is an abridged, 7-item version of the Inventory of Psychosocial Functioning (IPF) which assesses PTSD-related functional impairment in the prior 30 days across the same domains that are assessed by the 80-item version of the IPF; each item on the B-IPF corresponds to one IPF functional domain.8 About Post-Traumatic Stress Disorder PTSD is one of the most common mental health disorders in the United States, with approximately five percent of the population affected during a given year.2, 4, 9, 10 Most patients (>80%) with PTSD in the United States are in the civilian population.4, 11 It may occur in people who have experienced or witnessed a traumatic event, series of events or set of circumstances. An individual may experience an event that is emotionally or physically harmful or life-threatening which may affect mental, physical, social, and/or spiritual well-being. Examples of traumatic events include physical/sexual assault, natural disasters, serious accidents, terrorist acts, war/combat, historical trauma, intimate partner violence and bullying.12, 13 Symptoms of PTSD are generally grouped into four symptom clusters: intrusion (re-experiencing), persistent avoidance of stimuli, negative alterations in cognitions and mood, and marked alterations in arousal and reactivity. Individual symptom type and intensity can fluctuate over time and between individuals. To meet the criteria for PTSD diagnosis, symptoms must last longer than one month, and they must be severe enough to interfere with aspects of daily life, such as relationships or work. Symptoms also must not be due to medications, substance use, or another medical condition.10, 12 The average time from index trauma to symptom presentation is 2.2 years, and the average time from index trauma to PTSD diagnosis is 8.7 years.14 About Brexpiprazole Brexpiprazole was approved in the U.S. by the FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Most recently, brexpiprazole was approved in the U.S. for the treatment of agitation associated with dementia due to Alzheimer's disease, in May 2023. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively, and for agitation associated with dementia due to Alzheimer's disease in 2024. It was approved by the European Medicines Agency in 2018 for the treatment of schizophrenia and the Ministry of Health, Labour and Welfare in Japan for the treatment of schizophrenia and MDD in 2018 and 2023, respectively. Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown. Brexpiprazole has high receptor binding affinity to norepinephrine, serotonin and dopamine receptors. It is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors.15, 16 References 1. Davis LL, Behl S, Lee D, et al. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder. JAMA Psychiatry. Published online December 18, 2024. doi:10.1001/jamapsychiatry.2024.3996 2. U.S. Department of Veterans Affairs. How Common Is PTSD in Adults? Accessed September 2024. www.ptsd.va.gov/understand/common/common_adults.asp. 3. US Census Bureau. (2022). National Population by Characteristics: 2020-2022. Retrieved from www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html. 4. Lehavot K, Katon JG, Chen JA, Fortney JC, Simpson TL. Post-traumatic Stress Disorder by Gender and Veteran Status [published correction appears in Am J Prev Med. 2019 Oct;57(4):573]. Am J Prev Med. 2018;54(1):e1-e9. 5. Goldstein RB, Smith SM, Chou SP, et al. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016;51(8):1137-1148. 6. Schein J, Houle C, Urganus A, et al. Prevalence of post-traumatic stress disorder in the United States: a systematic literature review. Curr Med Res Opin. 2021;37(12):2151-2161. 7. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28-37. 8. U.S. Department of Veterans Affairs. Inventory of Psychosocial Functioning (IPF). Accessed December 2024. https://www.ptsd.va.gov/professional/assessment/functioning-other/ipf_psychosocial_function.asp 9. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H -U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169-184. 10. Lancaster CL, Teeters JB, Gros DF, Back SE. Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and Treatment. J Clin Med. 2016;5(11):105. 11. Davis LL, Schein J, Cloutier M, et al. The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective. J Clin Psychiatry. 2022;83(3):21m14116. 12. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013 13. American Psychiatric Association. What is Posttraumatic Stress Disorder (PTSD)? Last updated: November 2022. Last accessed: August 28, 2024. Available at: www.psychiatry.org/patients-families/ptsd/what-is-ptsd. 14. Davis LL, Urganus A, Gagnon-Sanschagrin P, et al. Patient journey of civilian adults diagnosed with posttraumatic stress disorder-A chart review study. Curr Med Res Opin. 2024;40(3):505-516. 15. Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589-604. 16. REXULTI® (brexpiprazole). Prescribing Information. FDA. Reference ID: 4911319. May 2024.

Clinical ResultPhase 3Drug Approval

04 Nov 2024

·www.biospace.com

7 Alzheimer’s and Parkinson’s Programs Discarded in 2024

iStock/ bawanch This year has seen several biopharma companies drop Alzheimer’s and Parkinson’s disease programs, but experts say plenty are still chasing these multi-billion-dollar markets. There’s no question that the approvals of Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla generated momentum in the Alzheimer’s disease treatment space. However, this year has seen attrition in the pipelines for both Alzheimer’s and Parkinson’s disease. Roche in particular has parted with several assets for Alzheimer’s disease, recently terminating a partnership with UCB. This is the second Alzheimer’s cut this year for the Swiss pharma, which in January returned two failed assets to AC Immune. Several other companies, including Johnson & Johnson, Sage Therapeutics and Otsuka Pharmaceuticals, have also dropped programs targeting Alzheimer’s and/or Parkinson’s. But Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, said this is not an indication of any major shifts in the R&D landscape but rather a “coincidence.” These decisions are “really dependent on data,” he told BioSpace . Several discarded Alzheimer’s and Parkinson’s programs, including AC Immune’s crenezumab, failed to produce positive data in clinical trials. “Maybe it’s also a reflection, sometimes, of what’s happening on the competitive landscape.” In terms of anti-amyloid antibody programs, such as crenezumab, Suvannevejh noted that despite the approvals of Leqembi and Kisunla, as well as Eisai and Biogen’s Aduhelm, this class has struggled to gain traction in the market. So companies may “have an evolving view of the commercial opportunity in Alzheimer’s disease,” he said. Overall, Suvannevejh said the pipelines of companies focused on Alzheimer’s disease are “okay.” While acknowledging that large pharmaceutical companies in this space do not have the “very rich, late-stage” pipelines they had three to five years ago, he said “there’s still a presence, because it is one of the few areas that could represent easily for any drug that gets approved, at least on paper, a multi-billion-dollar annual sales potential type of product.” The Alzheimer’s treatment space is projected to be worth $15.5 billion by 2031, according to iHealthcareAnalyst. As for Parkinson’s, Suvannevejh said there are around 20 therapies on the market that address the symptoms of the disease. There currently are none, however, that are disease-modifying because the underlying cause the disease is still unclear. While alpha-synuclein is the current candidate du jour , “we don’t have data yet,” he said. The global market for Parkinson’s disease drugs is currently valued at $5.56 billion and is expected to reach $6.63 billion by 2029. Parkinson’s is “still viewed as a very big commercial opportunity,” Suvannevejh said, “but so far, it’s been equally a difficult market to tap into.” Here, BioSpace takes a closer look at four companies that have recently discontinued programs for these two intractable neurodegenerative diseases. Roche Indication: Alzheimer’s disease Assets: Bepranemab, crenezumab, semorinemab In July 2020, Roche’s Genentech inked a collaboration with UCB to develop an anti-tau antibody treatment, bepranemab (UCB0107) for Alzheimer’s disease. Roche handed over $120 million upfront to UCB, with the Belgian company eligible for $2 billion based on certain regulatory approvals and other milestones. Four years later, that partnership is over. UCB revealed Roche’s decision while announcing the acceptance of an abstract for a Phase IIa study of bepranemab at the 2024 Clinical Trials on Alzheimer’s Disease conference, saying that the rights to the program had been handed back. No further details were provided. UCB isn’t the first company to receive a return from Roche this year. In January, the pharma ended its long-term collaboration with AC Immune, handing back two Alzheimer’s assets—anti-amyloid beta antibody crenezumab and anti-tau antibody semorinemab. In 2020, topline results from a Phase II trial of semorinemab showed the candidate failed to hit its primary endpoint, as well as two secondary endpoints, while crenezumab failed Phase II and III clinical trials in 2019 and 2022, respectively, according to Fierce Biotech . Long devoted to Alzheimer’s, Roche has struggled to gain a foothold in the space. A particular blow fell when gantenerumab, an investigational antibody, failed two Phase III studies in November 2022. This was the company’s second setback that year, following crenezumab’s failure to hit its co-primary endpoints in a Phase III for people with a specific gene mutation that causes early-onset Alzheimer’s. Despite all the bumps, Roche isn’t backing away from Alzheimer’s. Two other assets, RG6289 and trontinemab, are in Phase II studies. Roche touted positive data in March 2024 from a small Phase Ib/IIa study of trontinemab, reporting “rapid and robust” amyloid plaque reduction. Johnson & Johnson Indication: Alzheimer’s disease and Parkinson’s disease Assets: Seltorexant and JNJ-0376 A week before Roche parted ways with UCB, Johnson & Johnson slashed several pipeline programs in the neurology and psychiatry spaces, including seltorexant for Alzheimer’s disease and JNJ-0376 for Parkinson’s disease. Seltorexant, a human orexin-2 receptor blocker intended for the treatment of agitation or aggression in Alzheimer’s, was being studied in a Phase II trial. While a pipeline document on J&J’s website indicates it will no longer develop the drug for this indication, it will continue to evaluate seltorexant as a treatment for major depressive disorder with insomnia symptoms. Also on the chopping block was JNJ-0376, a Phase I Parkinson’s candidate the company had previously touted in a 2023 business overview presentation as having “novel mechanisms to modify, treat and/or prevent neurodegenerative disorders.” J&J did not provide further details on this program. Sage Therapeutics Indication: Alzheimer’s disease and Parkinson’s disease Asset: Dalzanemdor It hasn’t been a good year for Sage Therapeutics’ dalzanemdor. In April, the Cambridge, Mass.–based biopharma announced it would discontinue development of dalzanemdor in Parkinson’s disease after the oral drug candidate, which is intended to treat cognitive disorders associated with NMDA receptor dysfunction, failed a mid-stage trial. In the Phase II PRECEDENT study, which included 86 patients with Parkinson’s, dalzanemdor was found to be safe, but did not show any meaningful differences over placebo in any of the exploratory endpoints, including a cognition test. Six months later, dalzanemdor suffered another defeat, missing the primary endpoint in the Phase II LIGHTWAVE study in Alzheimer’s disease. According to Sage, trial data “did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo” on the same cognition test. Sage will halt further development of the asset in Alzheimer’s, according to an Oct. 8 press release . Sage has one remaining shot on goal with dalzanemdor. A Phase II study of the embattled candidate is ongoing in Huntington’s disease, with early data expected later this year. Otsuka Pharmaceutical Indication: Alzheimer’s-related agitation Asset: AVP-786 The pipeline of Japanese neuro player Otsuka Pharmaceutical is one candidate lighter after AVP-786 failed to improve agitation associated with dementia due to Alzheimer’s disease in a Phase III trial. Topline Phase III results in February 2024 showed the asset, which came to Otsuka in late 2014 in the $3.5 billion acquisition of Avanir Pharmaceuticals, did not show improvement over placebo in patients’ condition. The company announced in May it would end development of AVP-786. Otsuka is still developing brexpiprazole for agitation associated with dementia due to Alzheimer’s, which has been filed with regulatory authorities in Japan, according to the company’s pipeline document . Otsuka’s current pipeline includes candidates for schizophrenia, major depressive disorder and generalized anxiety disorder, among other psychiatric diseases, but does not list any other programs for Alzheimer’s.

Phase 2AcquisitionPhase 3Clinical Result

01 Nov 2024

·www.prnewswire.com

NeuroBlu: New Data Partner and Enterprise SSO Integration

Major expansion of behavioral health data with 940K+ new patient records, enterprise SSO integration, and enhanced analytics tools for deeper research insights. NEW YORK, Nov. 1, 2024 /PRNewswire/ -- Holmusk, a global leader in behavioral health real-world evidence, today announced the release of NeuroBlu Analytics v4.6, a major platform upgrade that combines expanded data coverage, enhanced analytics capabilities, and improved enterprise security through single sign-on (SSO) integration. This latest version of NeuroBlu reflects Holmusk's commitment to advancing behavioral health research and clinical insights by broadening access to quality, structured real-world data and strengthening analytical precision. A new partnership with a leading health provider network has added over 940,000 patient records from the New York City Metro area, increasing NeuroBlu's U.S. coverage to nearly 5 million patient encounters annually. This expanded dataset, integrated with Datavant tokenization, now enables pharmaceutical researchers to link granular psychiatric assessment data with claims outcomes, providing unprecedented insights into real-world treatment patterns and outcomes. "The most recent updates to NeuroBlu mark a transformative step forward in our ability to link clinical data with claims, unlocking insights that will drive better research and patient outcomes," said Holmusk CEO Nawal Roy. "With this powerful update to our new dataset, our platform enables researchers to make evidence-driven decisions in trial design, patient care, and health economics." Major Dataset Expansion The latest partnership expands NeuroBlu's reach into the Northeastern United States, adding comprehensive data for over 436,000 patients with anxiety disorders and 158,000 with major depressive disorder. Coverage includes key psychiatric medications, with insights into treatment sequences and real-world usage patterns. This unique dataset provides: Extensive Medication Data: 94% of patients have detailed medication history, covering commonly prescribed psychiatric medications like Vraylar (3,600+ patients) and Rexulti (2,200+ patients). Robust Geographic Representation: Coverage across NY, NJ, PA, CT, and FL enhances regional insights and relevance. Longitudinal Data and Vitals Tracking: Patients' treatment patterns and outcomes are tracked over time, offering a detailed view of treatment pathways and patient journeys. Claims Data Integration Through the integration of Datavant tokenization, NeuroBlu 4.6 enables the linkage of detailed psychiatric assessments with claims data, creating new possibilities for pharmaceutical research and health outcomes research. Key benefits include: Clinical Trial Optimization: Linking scales like PSS-3, PHQ-9, and GAD-7 with claims data enables researchers to optimize clinical trial design, track real-world treatment patterns across 940,000+ patients, and develop synthetic control arms. Evidence Generation: Linked datasets allow researchers to validate clinical endpoints, analyze medication adherence, and assess treatment discontinuation in real-world settings. These insights support augmentation strategies, examine concomitant medication use, and analyze healthcare utilization across diverse patient subgroups. Value Demonstration and HEOR Support: NeuroBlu's data-linking capabilities enable health economics and outcomes research (HEOR) by connecting clinical outcomes with cost data, examining treatment sequences, and enabling comparative effectiveness research. Long-term safety and effectiveness can now be tracked through linked datasets, strengthening insights into the value of mental health interventions. Enterprise-Grade Security with SSO Integration With the release of NeuroBlu Analytics v4.6, Holmusk introduces enterprise-grade single sign-on (SSO) integration, significantly enhancing security and access management for users. This new SSO functionality allows enterprise clients to securely and seamlessly access the NeuroBlu platform, meeting high-security standards and making user management more efficient for larger teams and organizations. Additionally, NeuroBlu 4.6 offers new SQL templates, allowing researchers to accelerate their data workflows, along with updated R and Python libraries featuring improved documentation for streamlined data integration. Together, these upgrades support researchers in extracting deeper insights with ease and efficiency, advancing NeuroBlu's mission to set new standards for security, usability, and innovation in behavioral health research. About Holmusk Holmusk is on a mission to harness real-world data to transform research and behavioral health care. Combining leading behavioral health data with AI-powered analytics and digital solutions designed to address the most pressing challenges in behavioral health, Holmusk is advancing the frontier of evidence generation and fueling innovation. Holmusk is headquartered in New York, with four additional offices worldwide. For more information, please visit . SOURCE Holmusk WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

100 Deals associated with Brexpiprazole

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KEGG	Wiki	ATC	Drug Bank
D10309	Brexpiprazole	N05AX16	DB09128

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Depressive Disorder	JP	Otsuka Holdings Co., Ltd.	22 Dec 2023
Agitation in Dementia	US	Otsuka Pharmaceutical Co., Ltd.	10 May 2023
Agitation	AU	Lundbeck Australia Pty Ltd.	19 May 2017
Alzheimer Disease	AU	Lundbeck Australia Pty Ltd.	19 May 2017
Depressive Disorder, Major	US	Otsuka Pharmaceutical Co., Ltd.	10 Jul 2015
Schizophrenia	US	Otsuka Pharmaceutical Co., Ltd.	10 Jul 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Psychotic Disorders	NDA/BLA	CN	Shanghai Xinfeng Pharmaceutical Co., Ltd.	16 Aug 2024
Stress Disorders, Post-Traumatic	NDA/BLA	US	Otsuka Pharmaceutical Development & Commercialization, Inc.	25 Jun 2024
Borderline Personality Disorder	Phase 3	US	Otsuka Pharmaceutical Development & Commercialization, Inc.	13 Jan 2020
Autism Spectrum Disorder	Phase 3	US	Otsuka Pharmaceutical Development & Commercialization, Inc.	30 Oct 2019
Autism Spectrum Disorder	Phase 3	US	H. Lundbeck A/S	30 Oct 2019
Bipolar I disorder	Phase 3	US	H. Lundbeck A/S	14 Sep 2017
Bipolar I disorder	Phase 3	US	Otsuka Pharmaceutical Development & Commercialization, Inc.	14 Sep 2017
Bipolar I disorder	Phase 3	BG	Otsuka Pharmaceutical Development & Commercialization, Inc.	14 Sep 2017
Bipolar I disorder	Phase 3	BG	H. Lundbeck A/S	14 Sep 2017
Bipolar I disorder	Phase 3	PL	H. Lundbeck A/S	14 Sep 2017

Clinical Result

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Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04124614 (Pubmed) Manual	Phase 3	Stress Disorders, Post-Traumatic	416	Brexpiprazole 2-3 mg + Sertraline 150 mg	mnqmtcmxsd(lprlhvrnsj) = orqbdnhucf wmjdhknivn (bzbfrhgpdh, 1.2) View more	Positive	18 Dec 2024
				Sertraline 150 mg + Placebo	mnqmtcmxsd(lprlhvrnsj) = stcvgtdgis wmjdhknivn (bzbfrhgpdh, 1.2) View more
NCT03737474 (BLESS, Pubmed \| CNS Drugs)	Phase 2/3	Depressive Disorder, Major	247	Brexpiprazole 2 mg/day	tncfuxdwju(eaiombbexm) = ajfdjsmwwo yirxguxwgm (dxnlnuyyvv ) View more	Positive	01 Dec 2024
NCT03620981 (CTgov)	Phase 2/3	Dementia due to Alzheimer's disease (disorder) \| Agitation	410	Placebo	ecozkasbex(lnjyiqnlzn) = tkqkehgbzy moxvbfomfi (ajodqrcwvk, tywoiwsdhc - xbbzkuintg) View more	-	14 Nov 2024
NCT03594123 (NCT03594123, Pubmed \| J Alzheimers Dis)	Phase 3	Dementia due to Alzheimer's disease (disorder)	259	Brexpiprazole 2 mg/day	pdvzlnbwew(wocskqgsdr) = xhijgquhiv aenvkwyudh (jiersciycs )	Positive	01 Nov 2024
NCT04186403 (CTgov)	Phase 2/3	Borderline Personality Disorder	201	Brexpiprazole	mdzgoxikpt(hlalscvjkq) = vuznslvnoq vkfezxerbq (jnmkdskjxy, gescvxsezz - iqvtiyravq) View more	-	03 Oct 2024
NCT03724942 (CTgov)	Phase 3	Dementia due to Alzheimer's disease (disorder) \| Agitation	164	brexpiprazole (ROLLOVER BREX)	uvhzozxgfm(ieqprhaafr) = wssxdpundp ihnptsqkbh (cejavlljlf, liqqyaibrn - gjtjvkumil) View more	-	19 Sep 2024
				placebo (ROLLOVER PLACEBO)	uvhzozxgfm(ieqprhaafr) = sqwlkpwzgj ihnptsqkbh (cejavlljlf, gakjufsqcd - zsvkvervzz) View more
NCT03697603 (CTgov)	Phase 2/3	Depressive Disorder, Major	740	Placebo	gwogpefuhu(oemdqmjocv) = vhbgmliwwh ixwwyoqrsh (rjzebnbwvw, hgnufuowmv - wlsgpcfrsq) View more	-	09 Aug 2024
NCT04100096 (CTgov)	Phase 2	Borderline Personality Disorder	332	Brexpiprazole (Brexpiprazole 2-3 Milligrams Per Day)	fqetlguzck(myeeyhqyph) = qtiaeczidb vbjorgcwpx (qxssrgglzy, tnwkrmvgyv - qxyutwdjiv) View more	-	18 Jul 2024
				Placebo (Placebo)	fqetlguzck(myeeyhqyph) = xtvozyhejw vbjorgcwpx (qxssrgglzy, szqrrjalyq - yudclugdnt) View more
NCT04258839 (CTgov)	Phase 3	Autism Spectrum Disorder \| Irritable Mood	95	Brexpiprazole (Prior Brexpiprazole)	lzdmsfxhic(kleyfcodyu) = enhakngifo sfbxdyhyep (tzepuoyzlu, ovlurutpxr - nmcnybmyhz) View more	-	30 May 2024
				placebo+brexpiprazole (Prior Placebo)	lzdmsfxhic(kleyfcodyu) = pohyesdgsr sfbxdyhyep (tzepuoyzlu, zcpupjbvdy - mfifbhxbpl) View more
NCT03033069 \| NCT04124614 \| NCT04174170 (331-201-00072, Biospace) Manual	Phase 2/3	Stress Disorders, Post-Traumatic	-	Brexpiprazole in combination with sertraline (331-201-061)	iukcugkofk(vpjrlnegxc) = ltnvfgtszg sdmxadosqg (dbwbqhgmtb )	Positive	28 May 2024
				sertraline plus placebo (331-201-061)	iukcugkofk(vpjrlnegxc) = hztimaobht sdmxadosqg (dbwbqhgmtb )

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