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The Effects of Valbenazine in Participants with Tardive Dyskinesia

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The Effects of Valbenazine in Participants with Tardive Dyskinesia SAFETY PROFILE In the extension period, valbenazine was generally well tolerated in a population of LONG-TERM TREATMENT WITH patients with diagnosed schizophrenia, schizoaffective disorder, or mood disorder.8 ONCE-DAILY VALBENAZINE MAY BE AN EFFECTIVE TREATMENT Treatment-emergent adverse events ≥5% in either valbenazine treatment group8,j FOR TD IN ADULTS WITH A • Headache (7.1%) • Dizziness (5.6%) • Urinary tract infection (6.6%) • Suicidal ideation (5.1%) RANGE OF PRESENTATIONS AND • Diarrhea (5.6%) • Depression (4.0%) TREATMENT HISTORIES8 j Combined valbenazine 40 mg and 80 mg once daily.8 • Valbenazine was generally well tolerated through 48 weeks, with There were no clinically important changes in clinical laboratory assessments, sustained TD reductions vital signs, or ECG parameters during the extension or washout periods.8 • TD symptoms tended to return to Psychiatric status generally remained stable during the extension study.8 baseline during the washout period, supporting the maintenance efficacy of ongoing valbenazine treatment LONG-TERM RESULTS AIMS mean score showed sustained TD reduction AIMS score reduction by ≥50% was generally through Week 488,9 consistent through Week 488 Extension study of valbenazine 40 mg and Percentage of extension study participants valbenazine 80 mg (ITT population)10 with AIMS responsel 1.0 100 90 0.0 -0.1 80 -1.0 -1.3 -1.1 -1.4 70 -1.8 -2.0 -2.3 60 -2.2 -2.9 52.4% -2.5 48.0% -3.0 -2.5 50 46.0% -3.0 P<0.001m -3.5 -3.5 40.0% 41.2% 40 -4.0 -4.2 m 28.8% 28.3% -4.2 -4.8 30 P<0.05 -4.3 -4.4 23.8% 23.4% mean score change from BL from change mean score -5.0 21.0% -5.0 19.7% 20 15.0% -5.5 -6.0 AIMS Patients with AIMS response (%) with AIMS response Patients 10 8.7% -7.0 0 BL 2 4 6 8 16 32 48 52 n 69 63 70 94 97 81 87 66 75 60 63 60 61 End of WEEK End of End of WEEK 6 n WEEK 8 WEEK 16 WEEK 32 WEEK 48 WEEK 52 DBPC Extension DFWO End of End of End of Placebo Valbenazine 40 mg Valbenazine 80 mg DBPC Extension Washout Re-randomized to valbenazine 40 mg Re-randomized to valbenazine 80 mg Number of patients Placebo 69 Placebo Re-randomized to VBZ 40 mg VBZ 40 mg 63 59 50 37 34 34 VBZ 40 mg Re-randomized to VBZ 80 mg VBZ 80 mg 70 67 58 50 43 41 VBZ 80 mg Re-randomized 32 29 27 24 24 to VBZ 40 mg Re-randomized 33 31 27 22 22 to VBZ 80 mg AT 48 WEEKS: ~39% TD reduction with valbenazine 80 mg9,k k In a post hoc analysis that included patients randomized to valbenazine 80 mg at baseline and those l AIMS response defined as ≥50% improvement from baseline AIMS dyskinesia score.8 who were re-randomized to valbenazine 80 mg at Week 6.9,10 m Not adjusted for multiplicity. Data presented for ITT analysis set. Treatment group comparison based AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DFWO, drug-free washout; on Cochran-Mantel-Haenszel test. P value vs placebo.8,9 iTT, intent-to-treat. n Intent-to-treat population. During the 4-week washout period, mean AIMS scores generally returned toward baseline.8 • Based on clinical assessment and need, continued valbenazine treatment may be required to maintain TD reductions FOR MORE INFORMATION, PLEASE VISIT INGREZZAHCP.COM Please see additional Important Safety Information throughout and full Prescribing Information in inside pocket. inside in Information Prescribing full and throughout Information Safety Important additional see Please ©2018 Neurocrine Biosciences, Inc. All Rights Reserved. CP-VBZ-US-0502 03/18 CP-VBZ-US-0502 Reserved. Rights All Inc. Biosciences, Neurocrine ©2018 operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA. by affected be will they how know they until machinery hazardous operating or vehicle motor a operating INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as as such alertness mental requiring activities perform not should Patients somnolence. cause can INGREZZA Somnolence WARNINGS & PRECAUTIONS & WARNINGS 10. 10. 9. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2017. Inc; Biosciences, Neurocrine CA: Diego, San insert]. [package INGREZZA Inc. Biosciences, Neurocrine file. on Data . 2017;78(9):1344-1350. 2017;78(9):1344-1350. Psychiatry Clin J study. extension 3 KINECT 1-year the of results dyskinesia: tardive with participants in valbenazine of effects IMPORTANT SAFETY INFORMATION SAFETY IMPORTANT 8. 8. Factor SA, Remington G, Comella CL, et al. The The al. et CL, Comella G, Remington SA, Factor 2017;174(5):476-484. Psychiatry J Am dyskinesia. tardive for valbenazine of trial placebo-controlled 7. 7. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, double-blind, randomized, 3 phase a 3: KINECT al. et SR, Marder SA, Factor RA, Hauser 1999;39(1):1-16. Res. Schizophr meta-analysis. and review 6. 6. Soares KV, McGrath JJ. The treatment of tardive dyskinesia—a systematic systematic dyskinesia—a tardive of treatment The JJ. McGrath KV, Soares 2014;4:266. (NY). Mov Hyperkinet Other Tremor clinic. disorder INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia. tardive with adults of treatment the for indicated is capsules (valbenazine) INGREZZA® Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement movement university-based a from experience agents: blocking receptor dopamine discontinuing after reversible rarely are syndromes Tardive INDICATION & USAGE & INDICATION 5. 5. Zutshi D, Cloud LJ, Factor SA. SA. Factor LJ, Cloud D, Zutshi 2017;78(3):e264-e278. Psychiatry Clin J meta-analysis. a use: antipsychotic second-generation of period the in 4. 4. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive dyskinesia prevalence prevalence dyskinesia Tardive CU. Correll JM, Kane CH, Hsieh M, Carbon 1975;41(2):97-104. Psychopharmalogia chlorpromazine. and loxapine Important Information Important et al. Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesia: effects of clozapine, haloperidol, haloperidol, clozapine, of effects dyskinesia: tardive of model a as rat the in receptors dopamine striatal of hypersensitivity Neuroleptic-induced al. et 3. 3. Sayers AC, Bürki HR, Ruch W, W, Ruch HR, Bürki AC, Sayers 2017. 1, February Accessed #c02598-5-1. htm&name=Chapter%205&title=Conventional%20antipsychotics Cambridge, UK: Cambridge University Press; 2013. http://stahlonline.cambridge.org/essential_4th_chapter.jsf?page=chapter5_introduction. 2013. Press; University Cambridge UK: Cambridge, 2. 2. 4th ed. ed. 4th . Psychopharmacology Essential Stahl’s SM. Stahl on: Based . Online Psychopharmacology Essential SM. Stahl 2014;11(1):166-176. References: 1. 1. References: . Neurotherapeutics disorder. common increasingly an for options therapeutic dyskinesia: Tardive SA. Factor D, Zutshi LJ, Cloud Supplementary section of article not provided as part of this reprint. this of part as provided not article of section Supplementary a . 2017;78(9):1344-1350. Psychiatry Clin J a Factor SA, Remington G, Comella CL, et al. al. et CL, Comella G, Remington SA, Factor KINECT 3 Extension Study. Extension 3 KINECT Results of the 1-Year 1-Year the of Results with Tardive Dyskinesia: Tardive with Please see inside pocket for full Prescribing Information or visit www.INGREZZAHCP.com. visit or Information Prescribing full for pocket inside see Please Valbenazine in Participants Participants in Valbenazine www.fda.gov/medwatch or call 1-800-FDA-1088. call or www.fda.gov/medwatch You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at at MedWatch Visit FDA. the to drugs prescription of effects side negative report to encouraged are You The Effects of of Effects The vomiting, nausea, and arthralgia. and nausea, vomiting, ≥ 2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, akathisia, headache, disorders/falls, balance effects, anticholinergic include: >placebo) and 2% ( reactions ≥ The most common adverse reaction ( reaction adverse common most The 5% and twice the rate of placebo) is somnolence. Other adverse adverse Other somnolence. is placebo) of rate the twice and 5% ADVERSE REACTIONS ADVERSE IMPORTANT SAFETY INFORMATION (continued) INFORMATION SAFETY IMPORTANT BACKGROUND SAFETY PROFILE Tardive dyskinesia (TD) is a chronic and potentially irreversible Valbenazine, a novel selective VMAT2 inhibitor, is an In the extension period, valbenazine was generally well tolerated in a population of LONG-TERM TREATMENT WITH drug-induced movement disorder.1 TD is associated with FDA-approved treatment indicated for adults with TD. In a patients with diagnosed schizophrenia, schizoaffective disorder, or mood disorder.8 ONCE-DAILY VALBENAZINE MAY prolonged exposure to dopamine receptor blocking agents pivotal, phase 3 study (KINECT 3), valbenazine 80 mg showed BE AN EFFECTIVE TREATMENT (DRBAs), including first-generation (typical) and significant improvements in TD severity at 6 weeks and had a Treatment-emergent adverse events ≥5% in either valbenazine treatment group8,j 2,3 7 FOR TD IN ADULTS WITH A second-generation (atypical) antipsychotics. generally well-tolerated safety profile. • Headache (7.1%) • Dizziness (5.6%) • Even with the advent of second-generation antipsychotics, VMAT2, vesicular monoamine transporter. • Urinary tract infection (6.6%) • Suicidal ideation (5.1%) RANGE OF PRESENTATIONS AND approximately 20% to 30% of patients with prolonged • Diarrhea (5.6%) • Depression (4.0%) TREATMENT HISTORIES8 4 STUDY OBJECTIVE exposure to DRBAs develop TD j Combined valbenazine 40 mg and 80 mg once daily.8 The KINECT 3 extension period evaluated the long-term safety and • Valbenazine was generally well • Dose reduction or discontinuation of the offending tolerability of once-daily valbenazine (40 mg or 80 mg) in adults with tolerated through 48 weeks, with There were no clinically important changes in clinical laboratory assessments, antipsychotic may not be effective and may exacerbate TD.
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