Brexpiprazole
- Generic Name
- Brexpiprazole
- Brand Names
- Rxulti, Rexulti
- Drug Type
- Small Molecule
- Chemical Formula
- C25H27N3O2S
- CAS Number
- 913611-97-9
- Unique Ingredient Identifier
- 2J3YBM1K8C
- Background
Brexpiprazole is an atypical antipsychotic and a novel D2 dopamine and serotonin 1A partial agonist called serotonin-dopamine activity modulator (SDAM). It has a high affinity for serotonin, dopamine and alpha (α)-adrenergic receptors. Although it is structurally similar to aripiprazole, brexpiprazole has different binding affinities for dopamine and serotonin receptors. Compared to aripiprazole, brexpiprazole has less potential for partial agonist-mediated adverse effects such as extrapyramidal symptoms, which is attributed to lower intrinsic activity at the D2 receptor. It also displays stronger antagonism at the 5-HT1A and 5-HT2A receptors.
Brexpiprazole was first approved by the FDA on July 10, 2015. Currently approved for the treatment of depression, schizophrenia, and agitation associated with dementia due to Alzheimer’s disease, brexpiprazole has also been investigated in other psychiatric disorders, such as post-traumatic stress disorder.
- Indication
Brexpiprazole is indicated as adjunctive therapy to antidepressants for the treatment of major depressive disorder in adults. It is also indicated for the treatment of schizophrenia in patients 13 years of age and older.
Brexpiprazole is also indicated for the treatment of agitation associated with dementia due to Alzheimer’s disease; however, it is not indicated as an as-needed (“prn”) treatment for this condition.
- Associated Conditions
- Agitation, Schizophrenia, Major Depressive Disorder (MDD)
Transneural Therapeutics Unveils Novel Non-Hallucinogenic Neuroplastogens for Neuropsychiatric Disorders
• Transneural Therapeutics has emerged from stealth mode with a preclinical pipeline of non-hallucinogenic neuroplastogens designed to treat neuropsychiatric and neurodegenerative diseases.
• The company's lead candidate, TN-001, is a dual 5-HT2A partial agonist/5-HT2B antagonist engineered to deliver rapid antidepressant effects without hallucinations, targeting major depressive disorder and PTSD.
• Industry veteran Charmaine Lykins, with 30 years of CNS drug development experience, will lead Transneural as CEO following its spin-out from CaaMTech.
2025 Pharmaceutical Pipeline: Major Patent Expirations Set to Transform Drug Market with Generics and Biosimilars
• The US pharmaceutical market is poised for significant change in 2025 as several blockbuster drugs including Xarelto, Entresto, and Stelara face patent expirations, opening the door to generic and biosimilar competition.
• Multiple biosimilars for ustekinumab (Stelara) are entering the market in 2025, with Wezlana already launched in January as the first interchangeable biosimilar, while other major drugs like ticagrelor and denosumab will also face competition.
• The pharmaceutical pipeline continues to expand with innovative therapies for cancer and neurological disorders, alongside the Medicare Drug Price Negotiation program which will further impact pricing dynamics for high-cost medications.
IGC Pharma Reports 78% Reduction in Sleep Disturbances with IGC-AD1 in Alzheimer's Phase 2 Trial
• Interim results from IGC Pharma's Phase 2 CALMA trial show IGC-AD1 reduced sleep disturbances by 71% at week 2 (p=.012) and 78% at week 6 (p=.02) compared to placebo in Alzheimer's patients.
• IGC-AD1, a cannabinoid-based partial CB1 receptor agonist, demonstrates potential as a safer alternative to current sleep medications for Alzheimer's patients, addressing a symptom that affects up to 44% of patients.
• The company plans to complete further analysis by end-2025 and is preparing additional studies to evaluate IGC-AD1 as a potential disease-modifying treatment for Alzheimer's disease.
European Commission Approves Rxulti for Adolescent Schizophrenia Treatment
• The European Commission has approved Rxulti (brexpiprazole) for treating schizophrenia in adolescents aged 13 years and older, expanding its previous 2018 approval for adults.
• Approval was based on a 6-week clinical trial of 316 adolescents showing significant symptom reduction as measured by PANSS scores, with a safety profile consistent with adult patients.
• Adolescent-onset schizophrenia often has poorer prognosis than adult-onset, with more chronic and severe symptoms, making this new treatment option particularly significant for young European patients.
FDA Approves Rexulti as Breakthrough Treatment for Alzheimer's-Related Agitation
• Lundbeck and Otsuka's Rexulti (brexpiprazole) becomes the first FDA-approved medication specifically for treating agitation in Alzheimer's disease patients, affecting approximately 50% of cases.
• Phase 3 clinical trials demonstrated Rexulti's efficacy with a 31% reduction in agitation symptoms compared to placebo, leading to FDA priority review approval.
• The approval could potentially increase Rexulti's annual sales by $500 million to $1 billion, adding to its current $1.4 billion revenue from existing indications in schizophrenia and major depressive disorder.
FDA Approves Monthly IV Maintenance Dosing for Leqembi, Eases Treatment Burden for Alzheimer's Patients
• The FDA has approved a monthly intravenous (IV) maintenance dose for Leqembi, offering a more convenient treatment schedule for early Alzheimer's disease.
• Patients completing the initial 18-month biweekly IV treatment can transition to monthly dosing, potentially improving long-term adherence and quality of life.
• Approval is based on data modeling showing sustained clinical and biomarker benefits with monthly dosing, addressing the continuous neurotoxic processes of Alzheimer's.
• Leqembi, developed by Eisai and Biogen, is now approved in multiple countries, offering a significant advancement in managing early Alzheimer's disease.
Schizophrenia Market Set for Strong Growth, Driven by Novel Therapies
• The schizophrenia market is expected to grow significantly, driven by the launch of novel therapies and increased diagnosis rates.
• Long-acting injectables (LAIs) are gaining traction despite higher costs, offering an alternative to oral antipsychotics.
• The US dominates the schizophrenia market due to a large patient population and high drug costs.
• Emerging treatments like Cobenfy, evenamide, Ingrezza, and iclepertin aim to address unmet needs in managing both positive and negative symptoms.
Amylyx Pharmaceuticals Appoints Dan Monahan as Chief Commercial Officer to Spearhead Avexitide Launch
• Amylyx Pharmaceuticals has appointed Dan Monahan as Chief Commercial Officer to lead the commercialization of their product portfolio.
• Monahan will focus on the potential approval and launch of avexitide, a GLP-1 receptor antagonist for post-bariatric hypoglycemia (PBH).
• Amylyx plans to initiate the Phase 3 LUCIDITY trial of avexitide in Q1 2025, with data expected in 2026, to address the unmet need for PBH treatment.
• Monahan brings over 20 years of experience in the biopharmaceutical industry, including successful launches at Otsuka, Novartis, and Sanofi.
Axsome's AXS-05 Shows Promise in Alzheimer's Agitation Trials, NDA Submission Planned for 2025
• Axsome Therapeutics' AXS-05 demonstrated a statistically significant delay in agitation relapse in Alzheimer's patients in the ACCORD-2 Phase 3 trial.
• The ADVANCE-2 trial did not meet its primary endpoint, but results numerically favored AXS-05, with a good safety profile across trials.
• Axsome plans to submit an NDA to the FDA in the second half of 2025, supported by data from four Phase 3 trials.
• AXS-05 has Breakthrough Therapy designation, potentially expediting its review for Alzheimer's disease agitation, a condition with limited options.
FDA to Review Rexulti for PTSD Treatment Amidst PDUFA Delay
• The FDA will convene a Psychopharmacologic Drugs Advisory Committee (PDAC) to review Rexulti (brexpiprazole) in combination with sertraline for treating PTSD in adults.
• The FDA's decision to host a PDAC meeting indicates a delay in the Prescription Drug User Fee Act (PDUFA) target action date, originally set for February 8, 2025.
• Clinical trial data supports the combination of brexpiprazole and sertraline, showing statistically significant improvements in PTSD symptoms compared to sertraline alone.
• Rexulti, developed by Otsuka and Lundbeck, is already approved for major depressive disorder, schizophrenia, and agitation associated with Alzheimer's disease.
Intra-Cellular Therapies Seeks FDA Approval for Caplyta in Major Depressive Disorder
• Intra-Cellular Therapies has submitted a supplemental New Drug Application to the FDA for Caplyta (lumateperone) as an adjunct treatment for Major Depressive Disorder (MDD).
• Caplyta, already approved for schizophrenia and bipolar disorder, demonstrated significant improvement in depression symptoms in Phase 3 trials when added to existing antidepressants.
• The application is supported by positive results from double-blind, placebo-controlled clinical trials in MDD patients who had an inadequate response to other antidepressants.
• If approved, Caplyta could become a first-choice add-on therapy for MDD, addressing a significant unmet need as over half of patients do not respond adequately to antidepressants alone.
Otsuka's Sibeprenlimab Shows Positive Phase 3 Interim Results for IgA Nephropathy
• Otsuka Pharmaceutical's sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatinine ratio (uPCR) compared to placebo.
• The Phase 3 VISIONARY trial met its primary endpoint after nine months of treatment in adults with IgA nephropathy.
• Otsuka plans to discuss the interim results with the FDA, potentially leading to an accelerated regulatory submission for sibeprenlimab.
• Sibeprenlimab targets APRIL, a key factor in the immune pathogenic cascade of IgA nephropathy, offering a potential new therapeutic strategy.
Lundbeck to Acquire Longboard Pharmaceuticals for $2.6 Billion, Bolstering Epilepsy Pipeline
• Lundbeck will acquire Longboard Pharmaceuticals for $2.6 billion, gaining bexicaserin, a promising drug for developmental and epileptic encephalopathies (DEEs).
• Bexicaserin, a 5-HT2C receptor superagonist, has shown encouraging results in clinical trials for reducing seizure frequency in Dravet syndrome and other DEEs.
• The acquisition aligns with Lundbeck's strategy to expand its neuro-rare disease portfolio, with bexicaserin potentially launching in 2028 and reaching peak sales of $1.5-2 billion.
• The deal is expected to close in the fourth quarter of 2024, pending regulatory approvals and tender of Longboard's outstanding shares.
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