A Clinical Study to learn if SEP-363856 has physical dependence in adults with schizophrenia. This study will be held in approximately 6 study sites in the United States. It will be accepting male and female participants age 18 years to 65 years. Participation will be up to approximately10 weeks.

Start Date21 Jun 2023

Sponsor / Collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

NCT05741528 / Enrolling by invitationPhase 3

An Open-label Extension Study to Assess the Safety and Tolerability of SEP-363856 in Subjects With Schizophrenia Switched From Typical or Atypical Antipsychotic Agents

An Extension study to a clinical study that will continue to evaluate the effectiveness and safety of SEP-363856 in people with schizophrenia that switch to SEP-363856 from their from their current antipsychotic medication. This study will accept both male and female participants that have completed study SEP361-308. This study will be held in approximately 24 study sites in North America. Participation in the study will be approximately up to 25 weeks.

Start Date31 Mar 2023

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

CTIS2022-500538-27-00 / Not yet recruiting

A Phase 2/3, Multicenter, Randomized, Double blind, Placebo controlled Trial of the Safety and Efficacy of Flexible Doses of SEP 363856 as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder. - 382-201-00001

Start Date30 Mar 2023

Sponsor / Collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

100 Clinical Results associated with Ulotaront

100 Translational Medicine associated with Ulotaront

100 Patents (Medical) associated with Ulotaront

Literatures (Medical) associated with Ulotaront

01 Sep 2024·Pharmacopsychiatry

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments

Review

Author: Takehara, Moe ; Hart, Xenia ; Uchida, Hiroyuki ; Komatsu, Yuki ; Hori, Satoko ; Takahashi, Yuna ; Ueno, Fumihiko

Abstract Introduction Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. Methods A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. Results Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. Discussion Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

01 Sep 2024·Pharmacology Biochemistry and Behavior

Ligands of the trace amine-associated receptors (TAARs): A new class of anxiolytics

Review

Author: Alnefeesi, Yazen ; Sukhanov, Ilya ; Gainetdinov, Raul R

Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics.

01 Jun 2024·Drug Development Research

SEP‐363856 exerts neuroprotection through the PI3K/AKT/GSK‐3β signaling pathway in a dual‐hit neurodevelopmental model of schizophrenia‐like mice

Article

Author: Li, Fujin ; Sun, Meng ; Zhang, Ling ; Liu, Yuexia ; Yang, Yating ; Liu, Huanzhong ; Li, Mengdie ; Liu, Yunxiao

AbstractSchizophrenia (SZ) is a serious, destructive neurodevelopmental disorder. Antipsychotic medications are the primary therapy approach for this illness, but it's important to pay attention to the adverse effects as well. Clinical studies for SZ are currently in phase ΙΙΙ for SEP‐363856 (SEP‐856)‐a new antipsychotic that doesn't work on dopamine D2 receptors. However, the underlying action mechanism of SEP‐856 remains unknown. This study aimed to evaluate the impact and underlying mechanisms of SEP‐856 on SZ‐like behavior in a perinatal MK‐801 treatment combined with social isolation from the weaning to adulthood model (MK‐SI). First, we created an animal model that resembles SZ that combines the perinatal MK‐801 with social isolation from weaning to adulthood. Then, different classical behavioral tests were used to evaluate the antipsychotic properties of SEP‐856. The levels of proinflammatory cytokines (tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β), apoptosis‐related genes (Bax and Bcl‐2), and synaptic plasticity‐related genes (brain‐derived neurotrophic factor [BDNF] and PSD‐95) in the hippocampus were analyzed by quantitative real‐time PCR. Hematoxylin and eosin staining were used to observe the morphology of neurons in the hippocampal DG subregions. Western blot was performed to detect the protein expression levels of BDNF, PSD‐95, Bax, Bcl‐2, PI3K, p‐PI3K, AKT, p‐AKT, GSK‐3β, p‐GSK‐3β in the hippocampus. MK‐SI neurodevelopmental disease model studies have shown that compared with sham group, MK‐SI group exhibit higher levels of autonomic activity, stereotyped behaviors, withdrawal from social interactions, dysregulated sensorimotor gating, and impaired recognition and spatial memory. These findings imply that the MK‐SI model can mimic symptoms similar to those of SZ. Compared with the MK‐SI model, high doses of SEP‐856 all significantly reduced increased activity, improved social interaction, reduced stereotyping behavior, reversed sensorimotor gating dysregulation, and improved recognition memory and spatial memory impairment in MK‐SI mice. In addition, SEP‐856 can reduce the release of proinflammatory factors in the MK‐SI model, promote the expression of BDNF and PSD‐95 in the hippocampus, correct the Bax/Bcl‐2 imbalance, turn on the PI3K/AKT/GSK‐3β signaling pathway, and ultimately help the MK‐SI mice's behavioral abnormalities. SEP‐856 may play an antipsychotic role in MK‐SI “dual‐hit” model‐induced SZ‐like behavior mice by promoting synaptic plasticity recovery, decreasing death of hippocampal neurons, lowering the production of pro‐inflammatory substances in the hippocampal region, and subsequently initiating the PI3K/AKT/GSK‐3β signaling cascade.

News (Medical) associated with Ulotaront

26 Aug 2024

·www.prnewswire.com

Schizophrenia Market: RISVAN's Approval Has Sparked a Competitive Race Among Pharmaceutical Companies | DelveInsight

The recent approval of Rovi Pharmaceuticals Laboratories' OKEDI/RISVAN (risperidone ISM) has spiked the competition among the other pharmaceutical companies that are developing novel therapies to improve the treatment landscape. RISVAN has the potential to become a blockbuster drug. LAS VEGAS, Aug. 26, 2024 /PRNewswire/ -- Schizophrenia is a severe mental illness affecting about 1% of Americans, cognitive functions, emotional responses, decision-making, and social interaction. Onset typically occurs in late teens to early 20s for men and late 20s to early 30s for women. Currently, as per the WHO, the vast majority of schizophrenia patients around the world are not receiving mental health care. Approximately 50% of people in mental hospitals have a schizophrenia diagnosis, and only 31.3% of people with psychosis receive specialist mental health care. As per DelveInsight analysis, in 2023 the total diagnosed prevalent cases of schizophrenia in the 7MM were found to be approximately 4 million cases out of which the US accounted for nearly 1.5 million cases. It is anticipated that these numbers will rise by 2034 due to several factors, including population growth, improved diagnostic techniques, increased awareness, and reduced stigma around mental health issues prompting more individuals to seek diagnosis, and potentially, environmental stressors contributing to a higher occurrence of the disorder. Schizophrenia treatment involves a blend of medication, psychological counseling, and social support. However, nearly one-third of patients do not respond sufficiently to standard treatments. Relapses, characterized by psychotic symptoms and functional impairments, are significant. Schizophrenia treatment mainly consists of antipsychotic medications that target dopamine neurotransmitters. Second-generation medications are favored because they lower the risk of severe side effects. Long-acting injectable antipsychotics can enhance adherence and improve treatment outcomes. High-dose regimens of specific medications may be advantageous for patients with severe, treatment-resistant schizophrenia. Additionally, hospitalization and electroconvulsive therapy might be necessary for patients who do not respond to medication therapy or during severe episodes. First-generation antipsychotics like chlorpromazine, fluphenazine, haloperidol, and perphenazine are effective in treating positive symptoms such as hallucinations and delusions but do not alleviate negative symptoms or cognitive impairments. Second-generation antipsychotics, including REXULTI/RXULTI (brexpiprazole), CAPLYTA (lumateperone), LATUDA (lurasidone hydrochloride), SAPHRIS (asenapine), ABILIFY MYCITE (aripiprazole tablets with sensor), VRAYLAR/REAGILA (cariprazine), SECUADO (asenapine), INVEGA SUSTENNA/TRINZA/HAYFERA (paliperidone palmitate), ARISTADA/ARISTADA INITIO (aripiprazole lauroxil), PERSERIS (risperidone), FANAPT (iloperidone), and LYBALVI (olanzapine and samidorphan), were developed to address both positive and negative symptoms, as well as cognitive symptoms. Although these medications typically have fewer extrapyramidal side effects, they can cause weight gain, sexual dysfunction, and other metabolic disorders. Additionally, elderly patients using FGAs and SGAs are at an increased risk of developing pneumonia. Learn more about the FDA-approved schizophrenia drugs @ Drugs for Schizophrenia Treatment REXULTI (brexpiprazole) is an oral tablet available in strengths from 0.25 mg to 4 mg, containing various inactive ingredients. While its exact mechanism of action is not fully understood, it work as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at serotonin 5-HT2A receptors. REXULTI was first approved in the US in July 2015 for use in adults with MDD and schizophrenia. In January 2022, it received FDA approval for pediatric patients aged 13–17. The EMA approved it in July 2018, and Japan approved it in tablet form in January 2018 and as an oral-disintegrating dose in August 2021. Generic versions of REXULTI have now been approved, which may affect its market presence. Janssen Pharmaceutical's INVEGA SUSTENNA/INVEGA TRINZA/INVEGA HAFYERA (paliperidone palmitate) is an SGA agent that seems to act as a D2 partial agonist and a 5-HT-2A receptor antagonist. INVEGA SUSTENNA is administered monthly, INVEGA TRINZA every three months, and INVEGA HAFYERA twice yearly. Paliperidone is a benzisoxazole derivative. In the EU and Japan, INVEGA SUSTENNA is marketed as XEPLION. In the EU, INVEGA TRINZA is sold as TREVICTA, and in Japan as XEPLION TRI. INVEGA HAFYERA is a long-acting injectable treatment administered in the upper buttocks every six months, providing continuous treatment and symptom control over this period. Additionally, the recent approval of RISVAN (Risperidone ISM) has intensified the competition in the schizophrenia treatment space. Risperidone ISM is a long-acting injectable antipsychotic created and patented by ROVI for treating schizophrenia in adults. From the first injection, it delivers immediate and sustained plasma drug levels without the need for loading doses or additional oral risperidone. This approval is based on the positive outcomes of the pivotal PRISMA-3 study, which assessed the efficacy and safety of Risperidone ISM in patients with schizophrenia. The study's findings demonstrate that the two doses tested (75 mg and 100 mg administered once monthly) successfully met the predetermined primary and secondary efficacy endpoints for treating patients with moderate to severe schizophrenia symptoms. Furthermore, OKEDI (risperidone ISM) was launched in Germany, the UK, and Spain in 2022. The approval was based on the positive results of the pivotal PRISMA-3 study on the efficacy and safety of risperidone ISM in schizophrenia patients. As per the estimates by Delveinsight analysts, this drug has blockbuster potential in the schizophrenia market with medium-fast uptake. To know more about schizophrenia treatment options, visit @ New Treatment for Schizophrenia The schizophrenia market is crowded with so many companies working in the domain. Various potential therapies that are projected to enter during the forecast period include Boehringer Ingelheim's Iclepertin (BI-425809), Sumitomo Pharma/Otsuka's Ulotaront (SEP-363856), Reviva Pharmaceuticals' Brilaroxazine (RP5063), Minerva Neurosciences/Mitsubishi Tanabe Pharma's Roluperidone (MIN-101/MT-210), Karuna Therapeutics (Bristol Myers Squibb)/Royalty Pharma's KarXT (xanomeline-trospium), ACADIA Pharmaceuticals' NUPLAZID (pimavanserin), Teva Pharmaceutical/MedinCell/Royalty Pharma's Olanzapine LAI (mdc-TJK/TV-44749), Neurocrine Biosciences/Mitsubishi Tanabe Pharma's Valbenazine (NBI-98854), Lyndra Therapeutics' LYN-005 (long-acting oral risperidone), Newron Pharmaceuticals' Evenamide (NW-3509), Luye Pharma's LY03010 (ER paliperidone palmitate), and others. Discover which therapies are expected to grab major schizophrenia market share @ Schizophrenia Market Report Iclepertin (BI 425809) is an investigational drug and a glycine transporter 1 (GlyT1) inhibitor aimed at addressing the brain biology related to cognitive symptoms in schizophrenia (CIAS). Abnormalities in glutamatergic signaling downstream of neuronal NMDA receptors contribute to cognitive impairment in this condition. Enhancing NMDA receptor function could potentially improve synaptic plasticity and cognition. Glycine, an essential NMDA receptor co-agonist, is modulated by glycine transporters GlyT-1 and GlyT-2, which are located in presynaptic and astrocyte membranes. These transporters regulate glycine levels by taking it up into nerve terminals and adjacent glial cells, affecting synaptic cleft glycine concentration. By inhibiting these transporters, BI 425809 aims to increase glycine levels, thereby modulating NMDA receptor function. Administered orally, this potent and selective GlyT1 inhibitor is also under investigation for Alzheimer's disease. However, early 2020 Phase II trial results did not support its continued development for this indication, and the focus has now shifted to schizophrenia, with multiple Phase III trials currently underway. Since schizophrenia, patients frequently ignore certain symptoms, such as cognitive impairment. Therefore, if approved, BI-425809 will be the first approved pharmacotherapy for the treatment of CIAS. Ulotaront (SEP-363856), developed by Sumitomo Pharma and Otsuka Pharmaceuticals, is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity. It is a small-molecule oral agent that does not bind to dopamine D2 or serotonin 5-HT2A receptors. Sunovion discovered Ulotaront in collaboration with PsychoGenics using the in vivo phenotypic SmartCube platform and associated artificial intelligence algorithms. Ulotaront is currently in late-stage development for schizophrenia and generalized anxiety disorder (GAD) in Japan and as an adjunctive treatment for major depressive disorder, schizophrenia, and GAD in the US. Top-line results from Phase III DIAMOND 1 and DIAMOND 2 trials in schizophrenia have been released, but the Phase III DIAMOND 3 trial in the US has been halted. Sumitomo Pharma has also stopped a Phase III trial for schizophrenia in Japan and another Phase II/III trial in China, Japan, Taiwan, and the Philippines, citing business strategy reasons. Despite this, two Phase III trials are still ongoing. Recently, Otsuka and Sumitomo revised their licensing agreement, excluding SEP-4199 and SEP-378614. Under this revision, Otsuka gained exclusive rights from SMPA to develop, manufacture, and commercialize ulotaront worldwide. If Otsuka successfully develops and commercializes ulotaront, they will pay up to 30 million USD (approximately 4.5 billion yen) in milestones, along with royalties based on sales, without any upfront payment. Starting January 2024, Otsuka will cover the full cost of studies conducted by both Sumitomo Pharma Group and Otsuka, except for certain studies. KarXT (xanomeline–trospium) is an oral modulator targeting muscarinic receptors found in both the central nervous system (CNS) and various peripheral tissues. This proprietary product combines xanomeline, a novel muscarinic agonist, with trospium, an approved muscarinic antagonist, to preferentially stimulate muscarinic receptors in the CNS. As a dual M1/M4 muscarinic acetylcholine receptor agonist, KarXT aims to improve the positive, negative, and cognitive symptoms of schizophrenia. The US FDA has accepted Karuna Therapeutics' NDA for KarXT for adult schizophrenia treatment, with a PDUFA date of September 26, 2024. Additionally, KarXT is undergoing multiple Phase III trials as an adjunctive treatment with standard-of-care agents for schizophrenia and is being evaluated for psychosis treatment in Alzheimer's disease patients. Following Bristol Myers Squibb's acquisition of Karuna Therapeutics, Karuna is now a wholly-owned subsidiary of BMS. At the Annual Congress of the Schizophrenia International Research Society (SIRS) in April 2024 in Italy, BMS presented promising results from the latest interim analysis of the Phase III EMERGENT-4 open-label extension trial, showing KarXT's efficacy in reducing symptoms in adults with schizophrenia. BMS plans to continue discussions with the US FDA and will release more data from the EMERGENT program later this year. Discover more about drugs for schizophrenia in development @ Schizophrenia Clinical Trials The anticipated launch of these emerging therapies for schizophrenia are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the schizophrenia market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for schizophrenia is expected to grow from USD 2.6 billion in 2023 with a significant CAGR by 2034. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the disease. The anticipated launch of these therapies is also expected to attract new entrants to the Schizophrenia market, resulting in increased competition and innovation. DelveInsight's latest published market report titled as Schizophrenia Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the schizophrenia country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The schizophrenia market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Prevalent Cases of Schizophrenia Total Diagnosed Prevalent Cases of Schizophrenia Gender-specific Diagnosed Prevalent Cases of Schizophrenia Severity-specific Diagnosed Prevalent Cases of Schizophrenia The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM schizophrenia market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this schizophrenia market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the schizophrenia market. Also, stay abreast of the mitigating factors to improve your market position in the schizophrenia therapeutic space. Related Reports Schizophrenia Pipeline Schizophrenia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key schizophrenia companies, including Otsuka Pharmaceutical Development & Commercialization, Inc., Gedeon Richter Ltd., Lyndra Therapeutics, Neurocrine Bioscience, Takeda Pharmaceutical Company, Memory Pharmaceuticals, Hoffmann-La Roche, Neurocrine Biosciences, Boehringer Ingelheim, Meiji Seika Pharma Co., Ltd., SK Life Science, Inc., Alkermes, Inc. , Solvay Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, SyneuRx International (Taiwan) Corp, BioXcel Therapeutics Inc, Cognitive Research Corporation, Amarex Clinical Research, Forum Pharmaceuticals Inc, Amneal Pharmaceuticals, LLC, Recognify Life Sciences, Accutest Research Laboratories (I) Pvt. Ltd., Eli Lilly and Company, Johnson & Johnson Pharmaceutical Research & Development, L.L.C, Janssen, LP, Delpor, Inc., Jiangsu Hansoh Pharmaceutical, Cerevel Therapeutics, LLC, Zogenix, Inc., Luye Pharma, Reviva Pharmaceuticals, Alkermes, Inc., Karuna Therapeutics, Autifony Therapeutics, Neumora Therapeutics, Adex Therapeutics, among others. Schizophrenia Epidemiology Forecast Schizophrenia Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and schizophrenia epidemiology trends. Dementia Market Dementia Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key dementia companies, including Hoffmann-La Roche, Forest Laboratories, Inc., Janssen Pharmaceuticals, Inc., Merck and Co., Inc., Novartis, among others. Bipolar Depression Market Bipolar Depression Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key bipolar depression companies, including Intra-Cellular Therapies, Sunovion Pharmaceuticals, COMPASS Pathways, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

Phase 3Phase 2Clinical ResultDrug ApprovalLicense out/in

05 Mar 2024

·firstwordpharma.com

Sumitomo’s US arm trims more jobs amid restructuring blitz

After axing around 500 positions at its US unit in July last year, Sumitomo Pharma announced another round of layoffs – this time slashing approximately 400 jobs, primarily in sales and marketing, as it intensifies efforts to restructure the subsidiary.The company cited the “current severe business environment” and the failure to achieve projected sales targets for three of its key products - Orgovyx (relugolix), Myfembree (relugolix/estradiol/norethisterone acetate), and Gemtesa (vibegron). Sumitomo recently revised down estimates for the drugs, with North American sales of Orgovyx in the current fiscal year seen reaching $290 million, down from an earlier prediction of $396 million.Meanwhile, annual revenue from Gemtesa in North America is now seen at $260 million, cut from previous guidance of $362 million, with Myfembree set to bring in $70 million, slashed from a prior forecast of $192 million. Jefferies analysts called the cuts to the outlook “bigger-than-expected,” noting that it is “increasingly unlikely” that the company will meet the targets of its “ambitious-looking medium term plan.”Sumitomo has also seen a significant revenue dip due to US patent expiry for the schizophrenia therapy Latuda (lurasidone). Sales of the product in North American plunged 97% in the third quarter of the current fiscal year to $5 million.Assets that the drugmaker hoped would replace lost revenue from Latuda have also stumbled in development. Last year, a pair of Phase III studies investigating the Otsuka-partnered schizophrenia candidate ulotaront failed to meet their primary endpoints. Sumitomo said recently that the development strategy for the drug in this indication continues to be discussed with Otsuka.

Phase 3NDAFinancial StatementBiosimilar

30 Oct 2023

·www.biospace.com

Otsuka’s Centanafadine Shows Promise in Phase III Pediatric ADHD Studies

Pictured: Girl student having trouble concentrating/iStock, PeopleImages Otsuka Pharmaceutical on Friday posted top-line data from two Phase III studies, demonstrating that its attention deficit/hyperactivity disorder candidate centanafadine significantly improves symptoms in children and teenagers. Friday’s readouts come from attention deficit/hyperactivity disorder (ADHD) trials that are largely similar in design, employing three arms and fixed high or low doses of centanafadine which were given compared to placebo on a double-blinded basis. The main difference is in the study populations: one enrolled adolescent participants between the ages of 13 and 17 years, while the other included children aged six to 12 years. In the adolescent study, patients treated with high-dose centanafadine saw significantly better scores on the ADHD Rating Scale version 5 (ADHD-RS-5), a validated tool used to assess the severity of ADHD and the study’s primary endpoint. The average effect of both the high and low centanafadine doses was also significantly better than placebo. Centanafadine was similarly effective in children. ADHD-RS-5 scores significantly improved in patients who were treated with high-dose centanafadine, and the average treatment effect in both high-dose and low-dose groups was likewise statistically better than placebo. In the adolescent and pediatric trials, the benefits of high-dose centanafadine became apparent as early as the first post-baseline timepoint at week one, which was sustained for the rest of the study periods. However, both low-dose arms did not see significantly improved ADHD-RS-5 scores versus placebo. In terms of safety, pooling data from both studies demonstrated a tolerability pro was consistent with centanafadine’s broader clinical development program. The most common side effects included nausea, upper abdominal pain, somnolence and fatigue. While the full results from both studies are not yet available, these data “demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD,” John Kraus, chief medical officer of U.S. subsidiary Otsuka Pharmaceutical Development and Commercialization, said in a statement. Otsuka will submit complete data and analyses from both trials for scientific publication. The company will also use these findings, along with clinical pharmacology studies and long-term stability data, to build a New Drug Application for centanafadine in this indication. Friday’s ADHD readout comes months after Otsuka and partner Sumitomo Pharma suffered two late-stage defeats in another psychiatric indication. In July 2023, the companies announced that its investigational TAAR1 agonist ulotaront failed the Phase III studies DIAMOND 1 and DIAMOND 2 in schizophrenia patients with acute psychosis. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Clinical Result

100 Deals associated with Ulotaront

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KEGG	Wiki	ATC	Drug Bank
-	Ulotaront	-	DB15665

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 3	UA	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Schizophrenia	Phase 3	RS	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Schizophrenia	Phase 3	CO	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Schizophrenia	Phase 3	RU	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Schizophrenia	Phase 3	BG	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Schizophrenia	Phase 3	US	Otsuka Pharmaceutical Development & Commercialization, Inc.	11 Sep 2019
Psychotic Disorders	Phase 1	CN	Sumitomo Pharma Co., Ltd.	29 Mar 2021
Psychotic Disorders	Phase 1	PH	Sumitomo Pharma Co., Ltd.	29 Mar 2021
Psychotic Disorders	Discovery	CN	Sumitomo Pharma Co., Ltd.	29 Mar 2021
Psychotic Disorders	Discovery	PH	Sumitomo Pharma Co., Ltd.	29 Mar 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


DIAMOND 1 (Corporate Publications) Manual	Phase 3	Schizophrenia	435	Ulotaront 50 mg/day	(wxercmbxjr) = tcoqdsscet cnafpxjkiy (obqaqyhmyn )	Negative	31 Jul 2023
				Ulotaront 75 mg/day	(wxercmbxjr) = yrioyajxoq cnafpxjkiy (obqaqyhmyn )
DIAMOND 2 (Corporate Publications) Manual	Phase 3	Schizophrenia	464	Ulotaront 75 mg/day	(tzqterkvpq) = jinepyrmqv bcmnhylhia (ktvldrubba )	Negative	01 Jul 2023
				Ulotaront 100 mg/day	(tzqterkvpq) = bfvyhzdyxa bcmnhylhia (ktvldrubba )
NCT02969369 (CTgov)	Phase 2	Parkinson Disease	39	SEP-363856	huaeecyhdh(pyxejvljrw) = qxrgnrzsqe pcxzvtxyge (wbfzsjtjrp, zvdrwarxpk - xllrkqhlrh) View more	-	05 Jun 2023
NCT02970929 (CTgov)	Phase 2	Schizophrenia	157	SEP-363856	adcdjbmrgf(vxdezjzoni) = wjseoklydl siwgcdimnm (pvcgffsknk, tajgkirrbk - ovdqcacjpj) View more	-	09 Feb 2022
NCT02969382 (CTgov)	Phase 2	Schizophrenia \| Psychotic Disorders	245	Placebo - Cap (Placebo)	llarlxdsfg(qmnbjyzrzi) = ayrvykmcqz akxcnbbyjp (ebqwjodozk, sdnidtwgax - ishaawwifh) View more	-	22 Sep 2021
				SEP-363856 (SEP-363856)	llarlxdsfg(qmnbjyzrzi) = zdcegwvrou akxcnbbyjp (ebqwjodozk, cgpvnuvblp - vynyfqxsym) View more
NCT02969382 (Pubmed \| Br Dent J) Manual	Phase 2	Schizophrenia	245	SEP-363856	(wxathyqwus) = hcnftpvcdn xlpyzvmpco (lcvrbzyxaw )	Positive	16 Apr 2020
				Placebo	(wxathyqwus) = ktdpzvgoze xlpyzvmpco (lcvrbzyxaw )

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