FDA Approves Otsuka and Lundbeck’s ABILIFY ASIMTUFII® (aripiprazole), the First Once-Every-Two-Months Long-acting Injectable (LAI) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults

Otsuka America Pharmaceutical, Inc. (Otsuka) and 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.

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Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. ABILIFY ASIMTUFII is not approved for the treatment of patients with dementia-related psychosis. ABILIFY ASIMTUFII is contraindicated with a known hypersensitivity reaction to aripiprazole. Please see Important Safety Information below.

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. ABILIFY ASIMTUFII, a long-acting injectable, provides continuous delivery of medication and can maintain therapeutic plasma concentrations, which may help those living with schizophrenia and bipolar I disorder.

“We are pleased to offer this new treatment option for people living with schizophrenia or bipolar I disorder,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. “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 comparable that demonstrated in studies with ABILIFY MAINTENA, a long-acting injectable, resulting in comparable safety and 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.”

About schizophrenia

Schizophrenia is a severely debilitating mental illness characterized by delusions, hallucinations, and disordered cognition.^1,2 Based on a systematic review of global data, the prevalence of schizophrenia in 2019 was estimated to be approximately 0.3% and did not vary widely across countries or regions.^3,4 The worldwide lifetime prevalence of the disease has been estimated to be approximately 0.9% across diverse geographic, cultural, and socioeconomic categories. The course of schizophrenia is typically characterized by acute episodes of psychotic behaviors occurring at varying intervals between periods of relative symptomatic stability.¹

About bipolar I disorder

Bipolar I disorder is a recurrent, lifelong mood disorder with a variable course that results in functional and cognitive impairment and a reduction in quality of life that affects 0.6% of the population.^5,6,7 The course of bipolar I disorder is characterized by recurrent manic and depressive episodes that may last weeks or months.⁸ Over 90% of people with bipolar disorder experience recurrences during their lifetimes.⁹

Bipolar I disorder often requires long-term pharmacologic treatment to delay time to recurrence.⁵ Long-acting injectables have the potential to provide continuous delivery of antipsychotic medication and can maintain therapeutic plasma concentrations, which may help address the variable nature of bipolar disorder.¹⁰

About ABILIFY ASIMTUFII (aripiprazole) once-every-two-months, long-acting injectable

ABILIFY ASIMTUFII (aripiprazole), once-every-two-months, long-acting injectable, is provided in a single-chamber, prefilled syringe (PFS) that does not require reconstitution. It is intended for dosing once-every-two-months via intramuscular (IM) injection in the gluteal muscle in the same patient populations as indicated for once-monthly ABILIFY MAINTENA.

Results from the pivotal trial 031-201-00181, that enrolled 266 patients, demonstrated that ABILIFY ASIMTUFII 960 mg met the primary endpoint criteria establishing similarity of aripiprazole plasma concentrations and thus comparable effectiveness to ABILIFY MAINTENA 400 mg over a two-month dosing interval.

Multiple-dose administrations of ABILIFY ASIMTUFII once-every-two-months, LAI 960 mg were generally safe and well tolerated in subjects with schizophrenia or bipolar I disorder and showed comparable safety to aripiprazole once-monthly 400 mg.

INDICATIONS and IMPORTANT SAFETY INFORMATION for ABILIFY ASIMTUFII^®(aripiprazole) and ABILIFY MAINTENA^® (aripiprazole)

INDICATIONS:

ABILIFY ASIMTUFII is a prescription medicine, 960 mg administered once every 2 months as a single injection, given by injection by a healthcare professional for:

• treatment of schizophrenia in adults
• maintenance treatment of bipolar I disorder in adults

ABILIFY MAINTENA is a prescription medicine, 300 mg or 400 mg administered once monthly as a single injection, given by injection by a healthcare professional for:

• treatment of schizophrenia in adults
• maintenance treatment of bipolar I disorder in adults

It is not known if ABILIFY ASIMTUFII or ABILIFY MAINTENA is safe and effective in children under 18 years of age.

IMPORTANT SAFETY INFORMATION:

Increased risk of death in elderly people with dementia-related psychosis. ABILIFY ASIMTUFII and ABILIFY MAINTENA increase the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). ABILIFY ASIMTUFII and ABILIFY MAINTENA are not for the treatment of people with dementia-related psychosis.

Do not receive ABILIFY ASIMTUFII or ABILIFY MAINTENA if you are allergic to aripiprazole or any of the ingredients in ABILIFY ASIMTUFII or ABILIFY MAINTENA.

ABILIFY ASIMTUFII or ABILIFY MAINTENA may cause serious side effects, including:

• Increased risk of stroke and ministroke has been reported in clinical studies with oral aripiprazole of elderly people with dementia-related psychosis and can lead to death.
• Neuroleptic malignant syndrome (NMS), a serious condition that can lead to death. Call your healthcare provider or go to the nearest emergency room right away if you have some or all of the following signs and symptoms of NMS: high fever, confusion, changes in pulse, heart rate, and blood pressure, stiff muscles, increased sweating.
• Uncontrolled body movements (tardive dyskinesia). ABILIFY ASIMTUFII and ABILIFY MAINTENA may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop receiving ABILIFY ASIMTUFII or ABILIFY MAINTENA. Tardive dyskinesia may also start after you stop receiving ABILIFY ASIMTUFII or ABILIFY MAINTENA.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia) and diabetes: Increases in blood sugar can happen in some people who are treated with ABILIFY ASIMTUFII or ABILIFY MAINTENA. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes such as being overweight or a family history of diabetes, your healthcare provider should check your blood sugar before you start treatment with ABILIFY ASIMTUFII or ABILIFY MAINTENA, and during your treatment.

Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with ABILIFY ASIMTUFII or ABILIFY MAINTENA:

• feel very thirsty
• need to urinate more than usual
• feel very hungry
• feel weak or tired
• feel sick to your stomach
• feel confused, or your breath smells fruity

• Increased fat levels (cholesterol and triglycerides) in your blood.
• Weight gain. You and your healthcare provider should check your weight regularly during treatment.

• Unusual and uncontrollable (compulsive) urges. Some people receiving ABILIFY ASIMTUFII or ABILIFY MAINTENA have had unusual strong urges, to gamble and gambling that cannot be controlled (compulsive gambling). Other compulsive urges include sexual urges, shopping, and eating or binge eating. If you or your family members notice that you are having unusual urges or behaviors, talk to your healthcare provider.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Falls. ABILIFY ASIMTUFII and ABILIFY MAINTENA may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause fractures or other injuries.
• Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment.
• Seizures (convulsions)
• Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. Do not drive a car, operate machinery, or do other dangerous activities until you know how ABILIFY ASIMTUFII or ABILIFY MAINTENA affects you. ABILIFY ASIMTUFII or ABILIFY MAINTENA may make you feel drowsy and affect your judgement, thinking, or motor skills.
• Problems controlling your body temperature so that you feel too warm. Do not become too hot or dehydrated during treatment with ABILIFY ASIMTUFII or ABILIFY MAINTENA. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water.
• Difficulty swallowing that can cause food or liquid to get into your lungs.

Do not drink alcohol while you receive ABILIFY ASIMTUFII or ABILIFY MAINTENA.

Before receiving ABILIFY ASIMTUFII or ABILIFY MAINTENA, tell your healthcare provider about all your medical conditions, including if you:

• have never taken aripiprazole before
• have or had diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start receiving ABILIFY ASIMTUFII or ABILIFY MAINTENA and during your treatment.
• have or had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low levels of HDL cholesterol
• have or had low or high blood pressure
• have or had heart problems or a stroke
• have or had a low white blood cell count
• have or had seizures (convulsions)
• have problems that may affect you receiving an injection in your buttocks (ABILIFY ASIMTUFII and ABILIFY MAINTENA) or arm (ABILIFY MAINTENA)
• are pregnant or plan to become pregnant. ABILIFY ASIMTUFII or ABILIFY MAINTENA may harm your unborn baby. If you become pregnant during treatment ABILIFY ASIMTUFII or ABILIFY MAINTENA, talk to your healthcare provider about the risk to your unborn baby and about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
• are breastfeeding or plan to breastfeed. ABILIFY ASIMTUFII or ABILIFY MAINTENA can pass into your milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you receive ABILIFY ASIMTUFII or ABILIFY MAINTENA.

Tell your healthcare provider about all the medicines you take, including prescription medicine and over-the-counter medicines, vitamins, and herbal supplements.

ABILIFY ASIMTUFII or ABILIFY MAINTENA and other medicines may affect each other causing possible serious side effects. Do not start or stop any medicines during treatment with ABILIFY ASIMTUFII or ABILIFY MAINTENA without talking to your healthcare provider first.

The most common side effects of ABILIFY ASIMTUFII or ABILIFY MAINTENA include: weight gain, restlessness or feeling like you need to move (akathisia), injection site pain, or sleepiness (sedation).

It is important to contact your healthcare provider if you experience prolonged, abnormal muscle spasms or contractions, which may be signs of a condition called dystonia.

These are not all the possible side effects of ABILIFY ASIMTUFII or ABILIFY MAINTENA.

If you have any questions about your health or medicines, talk to your healthcare provider.

You are encouraged to report side effects of ABILIFY ASIMTUFII and ABILIFY MAINTENA.

Please contact Otsuka America Pharmaceutical, Inc. at 1‑800‑438‑9927 or FDA at 1‑800‑FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING, and MEDICATION GUIDE for ABILIFY ASIMTUFII and ABILIFY MAINTENA.

About Otsuka

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs.

OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.1 billion in 2022.

All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/.

About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global biopharmaceutical company specialized in brain diseases. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best.

Our approximately 5,400 employees in more than 50 countries are engaged in the entire value chain throughout research, development, production, marketing and sales. Our pipeline consists of several R&D programs and our products are available in more than 100 countries. We have research centers in Denmark and California and our production facilities are located in Denmark, France and Italy.

In the United States, Lundbeck employs more than 1,000 people focused solely on accelerating therapies for brain disorders. With a special commitment to the lives of patients, families and caregivers, Lundbeck US actively engages in a broad range of initiatives each year that support patient communities.

For additional information, we encourage you to visit us at lundbeck.com/us, subscribe to our newsletter at Newsroom.LundbeckUS.com, and connect with us on LinkedIn and Twitter at @LundbeckUS.

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¹ American Psychiatric Association. What Is Schizophrenia.

² The National Institute of Mental Health. Schizophrenia.

³ World Health Organization. Schizophrenia.

⁴ The National Institute of Mental Health. Schizophrenia Statistics.

⁵ Bonnín CDM, Reinares M, Martínez-Arán A, et al. Improving Functioning, Quality of Life, and Well-being in Patients With Bipolar Disorder. Int J Neuropsychopharmacol. 2019;22(8):467-477. doi:10.1093/ijnp/pyz018

⁶ Dattani S., Ritchie H., and Roser M. Mental Health. Our World In Data. 2021.

⁷ Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241-251. doi:10.1001/archgenpsychiatry.2011.12.

⁸ The National Institute of Mental Health. Bipolar Disorder.

⁹ Leelahanaj T, Kongsakon R, Choovanichvong S, et al. Time to relapse and remission of bipolar disorder: findings from a 1-year prospective study in Thailand. Neuropsychiatr Dis Treat. 2013;9:1249-1256. doi:10.2147/NDT.S47711

¹⁰ Guzman F. Long-Acting Injectable Antipsychotics: A Summary for Prescribers. Psychopharmacology Institute. 2017.

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