Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Lundbeck Pharmaceuticals LLC (Lundbeck) announce the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for ABILIFY ASIMTUFII® (aripiprazole) extended-release injectable suspension for intramuscular use, a once-every-two-months injection for the treatment of schizophrenia in adults or for maintenance monotherapy treatment of bipolar I disorder in adults.

ABILIFY ASIMTUFII offers two months of sustained therapeutic concentrations with one dose. Each dose is provided in a single-chamber, prefilled syringe, and is administered by a healthcare professional to appropriate patients via intramuscular injection in the gluteal muscle. Long-acting injectables provide continuous delivery of antipsychotic medication and can maintain therapeutic plasma concentrations, which may help to maintain symptom control of schizophrenia and bipolar I disorder.

“We are pleased to offer this new treatment option for people living with schizophrenia or bipolar I disorder that may delay the time to relapse,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc. “This approval underscores Otsuka’s commitment to innovate and continuously evolve to meet the needs of the communities we serve.”

The efficacy of ABILIFY ASIMTUFII is based on the adequate and well-controlled studies of ABILIFY MAINTENA® (aripiprazole) in the treatment of schizophrenia or maintenance treatment of bipolar I disorder in adults. The aripiprazole concentrations of ABILIFY ASIMTUFII were explored in a pharmacokinetic bridging study which was a 32-week, open-label, multiple-dose, randomized, parallel-arm, multicenter study (N=266) in patients living with schizophrenia and bipolar I disorder. The once-every-two-months, long-acting injectable formulation in 960 mg and 720 mg prefilled syringes delivers sustained plasma concentrations similar to that demonstrated in studies with aripiprazole monohydrate once-monthly, long-acting injectable, resulting in similar sustained efficacy.

“This approval is important news for patients, families, and healthcare providers. We hope that the use of ABILIFY ASIMTUFII in treatment plans will have a positive impact on those living with schizophrenia or bipolar I disorder,” said Johan Luthman, executive vice president, R&D, Lundbeck. “We are grateful to the patients and researchers who made this major milestone possible.”

The Japan Sport Council (an independent administrative agency; Head office: Tokyo, Japan; President: Satoshi Ashidate; hereafter JSC) and Otsuka Holdings Co., Ltd. (Head office: Tokyo, Japan; President: Tatsuo Higuchi; hereafter Otsuka HD) have announced the August 2023 start of TCRP NEXT*1, a collaborative project for continued research into conditioning to enhance sustainable international competitiveness (high performance) in sports. Results of the ongoing research will be applied not only to boosting international competitiveness, but also to activities to raise awareness for enhanced life performance for members of the public at large.

The TCRP NEXT project will be managed by the JSC High Performance Sports Center (hereafter HPSC) and Otsuka Pharmaceutical Co., Ltd. (hereafter Otsuka Pharmaceutical). The new project will use Total Conditioning Guidelines for Athletes, compiled from results of the JSC High Performance Sports Center Total Conditioning Research Project, a joint industry, government, and academic research project aiming to promote sports medicine and boost Japan’s international competitiveness launched in December 2016. Knowledge developed for the new conditioning concept of “total conditioning” will be applied to achieve the following three objectives.

(1)Engage in conditioning-related research to enhance sustainable international competitiveness in sports.

(2)Apply results of research to public awareness activities in the realm of life performance (targeting the general population and members of the public at large).

(3)Consider updating the Guidelines as needed.

Objectives of TCRP NEXT

  • The Japan Sport Council (an independent administrative agency) and Otsuka Holdings Co., Ltd. have launched TCRP NEXT, a new collaborative project.
  • The project will publish Total Conditioning Guidelines for Athletes, based on results of research to date, providing an overview and information regarding the new “total conditioning” concept advocated by HPSC (publication scheduled for August 10, 2023).
  • The project will continue research into ways to boost sustainable international competitiveness in sports, with a focus on “total conditioning.
  • Information developed through various ongoing research projects will be used to maintain and promote public health, encouraging the transition from high performance to life performance.





Sumitomo Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President, and CEO: Hiroshi Nomura; Securities Code: 4506, First Section of TSE) and Otsuka Pharmaceutical Co., Ltd. (Head Office: Tokyo, Japan; president and representative director: Makoto Inoue) announced today that the DIAMOND (Developing Innovative Approaches for Mental Disorders) 1 clinical study and the DIAMOND 2 clinical study of ulotaront (generic name; development code: SEP-363856), a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A agonist activity, dosed once-daily in acutely psychotic adults living with schizophrenia did not meet their primary endpoint.

The multicenter, randomized, double-blind, parallel-group, fixed-dosed DIAMOND 1 study, evaluated the efficacy, safety, and tolerability of ulotaront (50 mg/day and 75 mg/day) versus placebo over six weeks in 435 acutely psychotic adults with schizophrenia.

In the DIAMOND 1 study all three groups showed a reduction in the Positive and Negative Syndrome Scale (PANSS) total score over time, however neither ulotaront treatment group was superior to placebo on the primary endpoint of change from baseline in PANSS total score at Week 6 (least squares [LS] mean: -16.9 and -19.6 in ulotaront 50 mg/day and 75 mg/day-treated patients, respectively, compared to -19.3 in placebo-treated patients).

The multicenter, randomized, double-blind, parallel-group, fixed-dosed DIAMOND 2 study, evaluated the efficacy, safety, and tolerability of ulotaront (75 mg/day and 100 mg/day) versus placebo over six weeks in 464 acutely psychotic adults with schizophrenia.

In the DIAMOND 2 study, ulotaront 75 mg/day and 100 mg/day treatment groups did not demonstrate statistically significant improvement compared to placebo on the primary endpoint. At Week 6 both ulotaront treatment groups showed numerically larger mean reductions in PANSS total score from baseline compared to placebo (LS mean: -16.4 and -18.1 in ulotaront 75 mg/day and 100 mg/day-treated patients, respectively, compared to -14.3 in placebo-treated patients).

In both the DIAMOND 1 study and the DIAMOND 2 study, a large placebo effect was observed which may have masked the molecule’s therapeutic effect.

Ulotaront was generally safe and well-tolerated in both studies.

Hiroshi Nomura, representative director, president and CEO of Sumitomo Pharma commented, “Sumitomo Pharma and our collaborator Otsuka Pharmaceutical have done preliminary analyses of the data and we believe that a high placebo response may have masked the therapeutic effect of this innovative molecule. High placebo responses, like those seen in DIAMOND 1 and DIAMOND 2, are well documented in psychiatric clinical studies. The placebo response in DIAMOND 1 was particularly high. These studies were conducted throughout the COVID-19 pandemic and initial analyses of these data suggest an impact of COVID-19 on the placebo responses that were seen. We continue to work closely with Otsuka and analyze the data to determine our next steps and plan to discuss with the U.S. FDA how to proceed based on these results.”

Makoto Inoue, president and representative director of Otsuka Pharmaceutical Co., Ltd. noted, “The two companies believe that ulotaront, as a new, potential treatment option in the future, can contribute to patients and healthcare professionals by addressing unmet needs in the treatment of schizophrenia. Based on these study results, Otsuka and Sumitomo Pharma will continue to collaborate to explore the full range of possibilities for ulotaront, as well to develop other drug candidates in the neuropsychiatric area, in order to contribute to patients suffering from psychiatric disorders worldwide.”

* Positive and Negative Symptom Scale (PANSS): An evaluation scale mainly intended to capture the overall mental status of individuals living with schizophrenia. It consists of a total of 30 symptom items including seven positive items, seven negative and 16 general psychopathology items. For each item the mental status is rated in a scale of 7 from 1 (no symptoms) to 7 (most serious).


About Ulotaront

Ulotaront, a TAAR1 agonist with 5-HT1A agonist activity, is currently under investigation for the treatment of schizophrenia (the DIAMOND 5 clinical study in Japan and China), generalized anxiety disorder (GAD) and the adjunctive treatment of major depressive disorder (MDD), with additional indications under consideration.

Ulotaront was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia in May 2019. Ulotaront is the first and only TAAR1 agonist to enter into Phase 3 clinical studies in people living with schizophrenia. It’s also the first TAAR1 agonist to enter into Phase 2/3 clinical studies in GAD, and as an adjunctive therapy in MDD.

Ulotaront is being jointly developed and commercialized as part of a collaboration between Sumitomo Pharma, its U.S. subsidiary Sumitomo Pharma America, Inc. (SMPA), and Otsuka.

SMPA discovered ulotaront in collaboration with PsychoGenics based in part on a mechanism-independent approach using the in vivo phenotypic SmartCube® platform and associated artificial intelligence algorithms.

About Trace Amine-Associated Receptor 1 (TAAR1)

Trace amine-associated receptor 1 (TAAR1) is a G-protein coupled receptor located in the central nervous system and periphery. TAAR1 – the first discovered in the TAAR family of receptors – is prominently expressed in areas of the brain involved in psychiatric disorders as well as in areas of the body that regulate energy metabolism. TAAR1 has shown the ability to affect dopamine, serotonin, and glutamate signaling, supporting its potential to modulate aspects of reward processing, cognition, and mood relevant to schizophrenia as well as other psychiatric disorders.

About Schizophrenia

Schizophrenia is a chronic, serious and often severely disabling brain disorder that affects more than 24 million people worldwide and over 2 million people in the United States.1,2 It is characterized by positive symptoms, such as hallucinations, delusions and disorganized thinking as well as negative symptoms, such as lack of emotion, social withdrawal, lack of spontaneity and cognitive impairment that includes problems with memory, attention and the ability to plan, organize and make decisions.3


1.Schizophrenia and Psychosis Action Alliance. Societal Costs of Schizophrenia & Related Disorders. Schizophrenia & Psychosis Action Alliance; 2021. Accessed June 10, 2022.
2.GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137-150. doi:10.1016/S2215-0366(21)00395-3
3.Rutigliano G, Accorroni A, Zucchi R. The case for TAAR1 as a modulator of central nervous system function. Front Pharmacol. 2018;8. Accessed October 4, 2022.

Otsuka Pharmaceutical Co., Ltd. (Otsuka) finalized a collaborative agreement with Tokushima Prefecture (Governor: Masazumi Gotoda) on July 27, aiming to contribute to realization of a sustainable society through promotion of horizontal “bottle-to-bottle*1” recycling of PET bottles. Working together with 12 participating municipal entities, Tokushima Prefecture aims to develop and promote “bottle-to-bottle” recycling initiatives.

July 27 signing ceremony at Tokushima Prefectural Government Office
(From left: Tokushima Prefecture Governor, Masazumi Gotoda;
Otsuka Pharmaceutical Tokushima Branch Office Manager, Ken Hosokawa)
  • Tokushima Prefecture’s First Agreement to Promote PET Bottle Resource Circulation through Horizontal Recycling Initiatives

Cooperative undertakings between Otsuka and local municipal entities, well-received by Tokushima Prefecture, facilitated the new agreement. By broadly promoting stable “bottle-to-bottle” resource circulation (horizontal recycling) of used PET bottles in Tokushima Prefecture, the agreement aims to reduce the volume of waste and promote efficient use of resources, contributing to the realization of a more sustainable society. Initiatives to promote public awareness and participation in resource circulation will include informative bottle-to-bottle posters and videos produced in cooperation with Tokushima Prefecture.

  • Promotion of Bottle-to-Bottle Initiatives in Cooperation with Municipal Entities in Tokushima Prefecture
Image of bottle-to-bottle recycling scheme

In advance of the agreement with Tokushima Prefecture, Otsuka concluded collaborative agreements for promotion of PET bottle resource circulation with municipal entities representing four cities and seven towns*2 in Tokushima, with the participation of Shikoku Godo Tsuun K.K. (Head office: Tokushima Prefecture; President: Rumi Sato) and Toyota Tsusho Corporation (Head office: Nagoya, Japan; President: Ichiro Kashitani).

Including the cooperative agreement finalized with Naruto City*3 in February 2023, Otsuka is now promoting bottle-to-bottle recycling with 12 local authorities, accounting for half of the municipal entities in Tokushima Prefecture.

Under the new agreement, the municipal entities will collaborate with government and corporate partners to collect used PET bottles, with collected bottles transported by Shikoku Godo Tsuun to Toyota Tsusho recycling facilities. Toyota Tsusho will process recycled bottles into high-quality PET material and Otsuka will use this material in production of PET bottles. The PET material will be used by Otsuka group companies and other beverage manufacturers. Through promotion of resource circulation in Tokushima Prefecture, the birthplace of the Otsuka group of companies, Otsuka aims to contribute to realization of a sustainable recycling society.

Concerned about limiting use of petroleum-based materials and promoting resource circulation, the soft drink industry*5 is working to develop horizontal bottle-to-bottle recycling, in which used PET bottles are reproduced as PET bottles for re-use. In the past, PET bottles discarded by households were recycled as food packaging trays, textiles, and other items, while PET bottles that did not meet the quality requirements for recycling were incinerated.

In recent years, technological innovations have made it possible to create high quality recycled PET resin*6 from used PET bottles, leading to expansion of horizontal bottle-to-bottle recycling initiatives.

With this technology, semi-permanent recycling of PET bottles is becoming a possibility, leading to reductions in consumption of petroleum-based resources and decreased CO2 emissions, which are expected to reduce the overall environmental impact of business activities.

Defining a Circular Economy as one of the material issues to be addressed by environmental policies, the Otsuka group has established the 2050 Environmental Vision, “Net Zero*7. The Otsuka Group Plastic Policy*8 was formulated with the aim of developing packaging suited for a sustainable society. In collaboration with stakeholders, Otsuka group companies are engaged in an extensive range of environmental initiatives.

In addition to “bottle-to-bottle” initiatives, Otsuka is adopting PET bottles made using 30% recycled PET resin, developing lighter packaging, reducing the volume of product packaging materials, offering label-free PET bottles and pursuing other environmentally conscious policies.

Striving to be an essential company that contributes to the health of people and the environment, Otsuka will continue to face challenges with innovation and creativity, aiming to realize a future society in which people and the earth can coexist in harmony.

  1. ※1    An ideal circular recycling system in which material from recycled PET bottles is used for production of PET bottles.
  2. ※2    Local towns and cities in order of finalization of agreement: Tsurugi, Awa, Kamiita, Itano, Naka, Higashimiyoshi, Miyoshi, Ishii, Kamiyama, Anan, Mima
  3. ※3    Otsuka has finalized a collaborative agreement with Naruto City and Toyota Tsusho aiming to contribute to realization of a sustainable society through promotion of horizontal
    recycling of PET bottles.
  4. ※4    Use of sustainable materials
  5. ※5    Reference: Japan Soft Drink Association
  6. ※6    PET resin produced from collected PET bottles by material recycling processes
  7. ※7    Otsuka Holdings Sustainability, Environment:
  8. ※8    Otsuka Group Plastic Policy:

Otsuka Holdings Co., Ltd. (Head office: Chiyoda-ku, Tokyo, Japan; President and Representative Director, CEO: Tatsuo Higuchi) has been recognized for leadership in corporate transparency and performance on climate change by global environmental non-profit CDP(*1), securing a place on its annual ‘A List’ for a second consecutive year. Otsuka also received an A- listing for water security, placing it at leadership level in the category.

Under its 2050 Environmental Vision, “Net Zero,” the Otsuka group is committed to reducing the total environmental impact of its business activities to zero. Based on this vision, we have determined carbon neutrality, and water neutrality as the part of the material issues in our environmental initiatives. In terms of carbon neutrality, group-wide collaboration is focused on meeting the group medium-term target of reducing CO2 emissions by 50% by 2028 compared to 2017, utilizing renewable energy by introducing solar power generation facilities and CO2 free electricity, improving energy use efficiency by introducing cogeneration systems(*2), and pursuing fuel conversion and other measures globally. In terms of water neutrality, we have conducted water risk assessment at the group’s all production sites worldwide in the aim of sustainable water use.

CDP is a global non-profit that runs the world’s environmental disclosure system for companies, cities, states and regions. The organization collects, analyzes, and evaluates information on the environmental activities of the world’s leading companies, and annually selects the best in terms of climate change initiatives and information disclosure for its climate change A List. In 2023, CDP scored more than 23,000 companies and selected 346 companies for its climate change A List.

The Otsuka group will continue to help build a decarbonized and sustainable world through the application of new technologies and solutions.