Austedo (deutetrabenazine) / Teva - LARVOL DELTA

Teva Reports Ninth Consecutive Quarter of Growth in Q1 2025 With Key Innovative Medicines Growing ~40%; 2025 Profit Outlook Improved (Teva Press Release) - "AUSTEDO – shows continued strong growth, with worldwide revenues of $411 million in Q1 2025, an increase of 39% in local currency terms compared to Q1 2024; increasing 2025 full-year revenue outlook from ~$1.9-2.05 billion to $1.95-2.05 billion. AJOVY – global revenues of $139 million in Q1 2025, an increase of 26% in local currency terms compared to Q1 2024. Reaffirming $600M 2025 revenue outlook. UZEDY continues strong momentum – global revenues of $39 million in Q1 2025."

Sales • CNS Disorders • Huntington's Disease • Migraine • Schizophrenia

Assessing Real-World Dosing Patterns for Vesicular Monoamine Transporter-2 Inhibitors (VMAT2i), Valbenazine and Deutetrabenazine, Among Patients with Tardive Dyskinesia (TD) in a Nationwide US Claims Database (ISPOR 2025) - "Persistent patients taking valbenazine experienced fewer month-to-month dose changes than deutetrabenazine patients, potentially representing a simpler treatment regimen for patients and providers. Additionally, over one-quarter of persistent deutetrabenazine patients on either formulation did not attain therapeutic dosing."

Claims database • Clinical • Real-world • Real-world evidence • CNS Disorders • Movement Disorders

Unique and overlapping mechanisms of valbenazine, deutetrabenazine, and vitamin E for tardive dyskinesia. (PubMed, Schizophrenia (Heidelb)) - "Pharmacological experiments should be conducted to verify and further explore these results. The findings offer a theoretical basis for further pharmacological investigation and a resource for TD drug screening."

Journal • Movement Disorders • DRD2 • NOS3 • SLC6A3 • TLR4

Indirect Treatment Comparison for Early Efficacy of VMAT2 Inhibitors for Tardive Dyskinesia and Chorea Associated with Huntington's Disease (ISPOR 2025) - "OBJECTIVES: Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for both tardive dyskinesia (TD) and chorea associated with Huntington's disease (HD). Favorable improvements were found with valbenazine versus deutetrabenazine during early treatment for both TD and HD-chorea. Magnitude of effect and time needed to reach an effective dose are important considerations when choosing a medication to treat the hyperkinetic movement disorders of TD or HD-chorea."

Clinical • Huntington's Disease • Movement Disorders

Huntington's disease treatment drug 'Austedo' expands indication for 'tardive dyskinesia' [Google translation] (HIT News) - "HanDok Teva...announced on the 25th that its Austedo tablet (ingredient: deutetrabenazine) received approval from the Ministry of Food and Drug Safety on the 9th for the indication of 'improving symptoms of tardive dyskinesia (TD)'....Austedo confirmed its therapeutic efficacy and safety in patients with tardive dyskinesia through two phase 3 clinical trials, 'AIM-TD' and 'ARM-TD.'"

Korea approval • CNS Disorders

The effect of deuterated PLK1 inhibitor on its safety and efficacy in vivo. (PubMed, Front Oncol) - "The FDA's approval of deutetrabenazine, the first deuterium-labeled drug, demonstrated an improved safety profile compared to its non-deuterated counterpart, tetrabenazine. The deuterated PR00012 demonstrated an improved safety profile and slightly enhanced efficacy compared to its non-deuterated counterpart, NMS-P937. This study provides a foundation for further clinical trials investigating the treatment of various cancers."

Journal • Preclinical • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Deutetrabenazine treatment outcomes with doses above U.S. Food and Drug Administration maximum approved doses in Huntington's disease chorea: A dual-site analysis. (PubMed, J Huntingtons Dis) - "The median total maximum chorea score in the Unified HD Rating Scale was 13 (IQR 9-19) and 13 (IQR 7-18) at baseline and follow-up, respectively. Median PDC was 0.99 (IQR 0.94-1.00); two patients discontinued therapy due to AEs.ConclusionsDeutetrabenazine >48 mg daily appears safe and well tolerated in patients with uncontrolled HD chorea, though no significant change in total maximal chorea score was found."

FDA event • Journal • Huntington's Disease • Movement Disorders • Psychiatry

Real-World Experiences with VMAT2 Inhibitors in Pediatric Hyperkinetic Movement Disorders (AAN 2025) - "Of 347 prescriptions for VMAT2 inhibitors, 94% were prescribed tetrabenazine, 4.6% deutetrabenazine and 1.4% valbenazine. Our study suggests that VMAT2 inhibitors are effective and safe for treating pediatric hyperkinetic movement disorders. While adverse effects were common, most were mild and improved with dosage reduction or transitioning to deutetrabenazine or valbenazine. Furthermore, this study provides insight into barriers to pediatric access."

Clinical • Real-world • Real-world evidence • Movement Disorders • Pediatrics

Effect Sizes of Once-daily Valbenazine for Tardive Dyskinesia: A Post-hoc Analysis of KINECT® 3 Data (AAN 2025) - P3 | "Effect sizes have been reported for common neuropsychiatric medications relative to placebo, including antidepressants for major depressive episodes (d=0.4), antipsychotics for schizophrenia (d=0.5), deutetrabenazine for TD (d=0.6), and levodopa for Parkinson's disease (d=0.9).Design/Cohen's d effect sizes for valbenazine in TD were calculated using Abnormal Involuntary Movement Scale (AIMS) data from KINECT® 3 (NCT02274558), a 6-week phase 3 study with valbenazine (40 or 80 mg) versus placebo. Based on AIMS data from KINECT 3, meaningful effect sizes were detected as early as Week 2 with a large effect size noted for valbenazine 80 mg by Week 6."

Retrospective data • CNS Disorders • Depression • Huntington's Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Cost Trends of New-To-Market Neurologic Medications: An Insurance Claims Database Analysis. (PubMed, Neurology) - "NTM medications for neurologic conditions have substantial and increasing individual and societal costs, which was not observed for older generic medications. These data suggest a need for policies to limit the financial burden of NTM medications on patients with neurologic conditions."

Journal • Reimbursement • US reimbursement • Amyloidosis • Amyotrophic Lateral Sclerosis • Cardiac Amyloidosis • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Huntington's Disease • Hypotension • Migraine • Movement Disorders • Muscular Dystrophy • Myasthenia Gravis • Pain • Rare Diseases

Efficacy of Deutetrabenazine to Control Symptoms of Dysphagia Associated with HD (clinicaltrials.gov) - P1 | N=36 | Terminated | Sponsor: Fundacion Huntington Puerto Rico | Not yet recruiting ➔ Terminated; The study was terminated prematurely due to the lack of availability of the study drug.

Trial termination • Gastrointestinal Disorder • Genetic Disorders • Huntington's Disease • Movement Disorders

Real-world safety analysis of deutetrabenazine post-marketing: a disproportionality study leveraging the FDA Adverse Event Reporting System (FAERS) database. (PubMed, BMC Pharmacol Toxicol) - "This research has yielded initial safety insights into the practical use of deutetrabenazine, validating established adverse reactions and uncovering further possible risks. These findings present essential safety considerations for physicians when prescribing deutetrabenazine for the clinical treatment."

Adverse events • Journal • P4 data • Real-world evidence • Retrospective data • CNS Disorders • Depression • Fatigue • Huntington's Disease • Insomnia • Movement Disorders • Psychiatry • Sleep Disorder • Suicidal Ideation

A narrative review of phase III and IV clinical trials for the pharmacological treatment of Huntington's disease in adults. (PubMed, Medicine (Baltimore)) - "The medications used in phase III and IV trials are minocycline, valbenazine, deutetrabenazine, tominersen, pridopidine (phase III), and memantine (phase IV)...Current medications aim to manage HD symptoms, potentially improving outcomes and reducing disease progression risks. The growing emphasis on specific approaches reflects a better understanding of HD's diverse symptoms, presenting opportunities for more effective and personalized treatment strategies."

Journal • P3 data • Review • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

The Huntington's disease drug pipeline: a review of small molecules and their therapeutic targets. (PubMed, Prog Mol Biol Transl Sci) - "Two small molecules, Tetrabenazine and Deutetrabenazine, are approved for managing chorea associated with HD, and several others are under clinical trials. The emphasis is placed on detailing their structural design, therapeutic effects, and specific mechanisms of action. Additionally, exploring key drivers implicated in HD pathogenesis offers valuable insights, as a foundational principle for designing prospective anti-HD therapeutic leads."

Journal • Review • CNS Disorders • Huntington's Disease • Movement Disorders

Teva Delivers Second Consecutive Year of Growth; Announces Strong Financial Results in Fourth Quarter and Full Year 2024, Led by Generics Performance and Innovative Portfolio Growth (GlobeNewswire) - "Duvakitug (Anti-TL1A) positive Phase 2B results announced and initiation of Phase 3 program is expected in 2025...AJOVY revenues in our United States segment in the fourth quarter of 2024 were $63 million, an increase of 11% compared to the fourth quarter of 2023...AUSTEDO revenues in our United States segment in the fourth quarter of 2024 increased by 27%, to $518 million, compared to $408 million in the fourth quarter of 2023...UZEDY (risperidone) extended-release injectable suspension revenues in our United States segment in the fourth quarter of 2024 were $43 million...COPAXONE revenues in our United States segment in the fourth quarter of 2024 were $63 million, a decrease of 13% compared to the fourth quarter of 2023, mainly due to market share erosion and competition, partially offset by a reduction in sales allowance."

Commercial • New P3 trial • CNS Disorders • Crohn's disease • Huntington's Disease • Migraine • Multiple Sclerosis • Schizophrenia

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease. (PubMed, CNS Drugs) - P3 | "In this open-label, long-term study, some participants received deutetrabenazine dosing > 48 mg/d to achieve adequate chorea control. There was no new safety concern or incremental change in the safety profile between dosages of ≤ 48 mg/d and > 48 mg/d. These results include dosages that have not been approved for clinical use, however, they increase our understanding of safety and tolerability of deutetrabenazine doses."

Journal • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

Valbenazine for the treatment of chorea associated with Huntington's disease. (PubMed, Expert Opin Pharmacother) - "Even though multiple classes of medications have been used to treat this symptom, only the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine have been approved by the FDA for this indication. The cost of this medication could be a barrier to access, even for those with insurance, due to high co-pay fees. Head-to-head clinical trials are needed to compare valbenazine's efficacy with the other approved drugs for chorea in HD."

Journal • Review • CNS Disorders • Huntington's Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Navigating the deuteration landscape: innovations, challenges, and clinical potential of deuterioindoles. (PubMed, Chembiochem) - "This review elucidates the progression of deuterium chemistry, culminating in approval of Deutetrabenazine in 2017. This milestone has catalyzed additional research into deuterated indoles, such as Dosimertinib, which have demonstrated enhancements in stability, toxicity profiles, and therapeutic efficacy. Moreover, the review addresses challenges and patent issues in the synthesis of deuterated indoles and highlights their potential applications in precision medicine. In the future, deuterated indoles may positively impact therapy and contribute to advances in precision medicine through molecular engineering."

Journal • Targeted Protein Degradation

Efficacy and acceptability of pharmacological interventions for tardive dyskinesia in people with schizophrenia or mood disorders: a systematic review and network meta-analysis. (PubMed, Mol Psychiatry) - "In network 2 (k = 2, n = 63), switch to molindone (k = 1, n = 9) versus switch to haloperidol worsened TD (SMD = 1.68; 95% CI = 0.61,2.76)...Despite large effect sizes for some treatments with very low quality/confidence, when considering higher quality evidence only valbenazine or deutetrabenazine are evidence-based first-line treatments for TD, and potentially vitamin E as second-line. Switching to molindone and antipsychotic washout should be avoided. More treatment options and higher-quality trials are needed."

Journal • Retrospective data • Review • CNS Disorders • Mood Disorders • Movement Disorders • Psychiatry • Schizophrenia

Teva Announces Strong Financial Results for the Third Quarter of 2024, led by Generics Performance and Innovative Portfolio Growth; Raises 2024 Financial Outlook including on Revenues, Adjusted EBITDA and Non-GAAP EPS (Teva Press Release) - "AUSTEDO – shows continued growth, U.S. revenues of $435 million in Q3 2024, an increase of 28% compared to Q3 2023; reaffirming 2024 revenue outlook of ~$1.6 billion....AJOVY – global revenues of $137 million in Q3 2024, an increase of 21% in local currency terms compared to Q3 2023."

Commercial • CNS Disorders • Huntington's Disease • Migraine

Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease (clinicaltrials.gov) - P2/3 | N=30 | Recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

Effectiveness and Satisfaction with Deutetrabenazine in Huntington Disease When Initiated Using a 4-Week Patient Titration Kit: Final Results of the START Study (HSG 2024) - "The titration kit enabled patients to titrate to optimal deutetrabenazine dosages with effectiveness similar to that of pivotal clinical trials [2, 3] and with high patient and HCP satisfaction.ABSTRACT SUMMARY: The START study evaluated real-world usage of deutetrabenazine when initiated using a 4-week patient titration kit. As of this final analysis, 76% of patients with Huntington disease–associated chorea successfully completed the kit, with a mean adherence rate of 92%. 50% of patients achieved treatment success, and 100% of responding patients found it easy to use the kit."

Clinical • Genetic Disorders • Huntington's Disease • Movement Disorders

SPK-10001 AAV-Based MicroRNA Mediates Non-Allele Specific Reduction of HTT mRNA through RNA Interference, Demonstrating its Potential for Further Preclinical Development (HSG 2024) - "Although several drugs are specifically approved for treatment of chorea in HD patients (Tetrabenazine, Deutetrabenazine, and Valbenazine), there are no treatment options for worsening function or overall clinical disease progression of HD. SPK-10001 induced a well-tolerated and stable reduction of up to 40% in HTT mRNA and up to 70% in HTT protein levels over twelve months period. In summary, the preliminary preclinical data showed no adverse effects associated with the reduction of HTT mRNA and protein levels and supports further preclinical development of SPK-10001."

Preclinical • CNS Disorders • Gene Therapies • Huntington's Disease • Movement Disorders

Persistent Tic Disorders: Practical Tips on When, What, and How to Treat (AACAP 2024) - "Although haloperidol, pimozide, and aripiprazole are the only FDA-approved medications labeled for treatment of Tourette's disorder in the United States, these are associated with intolerable adverse effects...Topiramate, clonazepam, deutetrabenazine, or baclofen can be used off-label, and there are compounds under investigation, such as ecopipam. Pragmatic approaches to pharmacotherapy for tic disorders involve disentangling and prioritizing target symptoms. Developing a systematic evaluation and hierarchical method is essential.TICD, PDS, TREAT"

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome

Exploring the Role of Deutetrabenazine in the Treatment of Chorea Linked with Huntington's Disease. (PubMed, Curr Rev Clin Exp Pharmacol) - "Here we highlight, Deutetrabenazine as a promising new treatment for Huntington's disease chorea, for patients with chorea, deutetrabenazine offers hope for an enhanced quality of life. To completely understand its effectiveness and potential advantages, additional research is necessary, including direct comparison studies, as a result of the mixed study results."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders