Dosing, Patterns, Effectiveness, and Treatment Satisfaction with Deutetrabenazine When Initiated Using a 4-Week Patient Titration Kit: Interim Results of the START Study

Introduction Deutetrabenazine is a vesicular monoamine transporter type 2 inhibitor (VMAT2i) for treatment of adults with tardive dyskinesia (TD) and Huntington disease (HD)-related chorea. A 4-week patient titration kit was launched (July 2021) to assist patients in titrating to optimal deutetrabenazine dosages. Methods START is an ongoing, routine-care, 2-cohort (TD and HD) study evaluating deutetrabenazine dosing patterns, effectiveness, and treatment satisfaction when initiated using a 4-week patient titration kit, with further titration allowed based on effectiveness and tolerability. Patient satisfaction with the kit was assessed via questionnaire at week 8. Results from the first 50 patients enrolled in the TD cohort are presented in this interim analysis. Results 50 patients in the TD cohort were included (mean age, 58.7 years, 66% female, 74% White, mean baseline Abnormal Involuntary Movement Scale [AIMS] total motor score, 13.8). 39 of 50 (78%) patients successfully completed the titration kit (completed within 5 weeks or reached optimal dose [≥24 mg/day] within 4 weeks; mean [SE] days, 27.5 [0.32]). Mean (SE) time to reach optimal dosage for the 38 (76%) patients who reached it was 46.3 (5.48) days. Mean (SE) deutetrabenazine dosages were 27.7 (0.92) mg/day at week 4, 32.5 (1.00) mg/day at week 8, and 32.8 (1.18) mg/day at week 12. After completion of the kit, mean (SE) dosage was 31.8 (1.24) mg/day, and 95% of patients reaching week 12 had a maintenance dosage ≥24 mg/day. Mean (SE) adherence with the kit was 97.2% (1.39%). 22% of patients had an adverse event (AE); AEs led to dose reduction for 2%, drug interruption for 2%, and study discontinuation for 6% of patients. Serious and treatment-related adverse events were reported for 2% and 6% of patients. 24 of 49 (49%)23 of 49 patients achieved treatment success (“much”/“very much” improved) at week 12 per Clinical Global Impression of Change (GIC); 23 or 49 (47%) per Patient GIC. Total motor AIMS scores were reduced by 4.8 points at week 12. Among the 39 (78%) patients who responded to the questionnaire, 72% found it easy to understand when/which dosage to take, 77% easy to remember to take their medication, 74% easy to change the dose weekly, 69% easy to follow kit instructions, and 77% easy to use the kit overall. Conclusions 78% of patients with TD successfully completed the 4-week titration kit in approximately 4 weeks, with adherence rates of 97.2%. 95% of patients reaching week 12 had a maintenance dosage ≥24 mg/day. 49% of patients achieved treatment success based on Clinical GIC. Patients reported high levels of satisfaction with the titration kit and 77% found it easy to use. The 4-week patient titration kit enabled patients to titrate DTBZ to an optimal dosage and experience effectiveness similar to the pivotal clinical trials. Funding Teva Branded Pharmaceutical Products R&D, Inc.