Statistically significant improvement over placebo across multiple endpoints in patients with HD chorea1-3

AUSTEDO reduced total maximal chorea (TMC) score by 4.4 points from baseline (P<0.0001)1

FIRST-HD Primary Endpoint: Change in TMC Score From Baseline to Maintenance Therapy (N=90, ITT)1,2

FIRST-HD: Total Maximal Chorea (TMC) score from baseline to maintenance therapy (N=90, ITT), >2x improvement in TMC score seen with AUSTEDO vs placebo. FIRST-HD: Total Maximal Chorea (TMC) score from baseline to maintenance therapy (N=90, ITT), >2x improvement in TMC score seen with AUSTEDO vs placebo.

>2x IMPROVEMENT

in TMC score seen with AUSTEDO vs placebo

ITT, intent-to-treat.

  • 33% of patients treated with AUSTEDO achieved a ≥6-point improvement in TMC score compared to 2% of patients treated with placebo2

The TMC score quantifies choreic movements of the face, mouth, trunk, both arms, and both legs, resulting in an overall score for the 7 regions that is based on independent visual review.2

ARC-HD: the longest HD chorea trial to date3,4

In the longest chorea trial to date for this progressive disease (open-label extension, non-blinded)3,4

Mean TMC scores decreased from baseline to Week 8 with results maintained through ~3 years3

TMC reductions were seen in both the Rollover and Overnight Switch from tetrabenazine cohorts.3*

  • In patients who rolled over from the pivotal study, there was a 4.4-point reduction at Week 8
  • In patients who switched overnight from tetrabenazine, there was a 2.1-point reduction at Week 8

Reductions were maintained in both cohorts from Week 8 to Week 132.

*ARC-HD was divided into 2 study cohorts: patients who rolled over from the pivotal trial and patients who switched overnight from tetrabenazine.3

AUSTEDO reduced total motor score (TMS), improving control of motor function2

FIRST-HD: LS Mean Change in TMS From Baseline to Maintenance Therapy (N=90, ITT)2

FIRST-HD: Change in Total Motor Score (TMS) from baseline to maintenance therapy (N=90, ITT), >2x reduction in total motor function impairment with AUSTEDO vs placebo (P=0.0002).

>2x REDUCTION

in total motor function impairment with

AUSTEDO vs placebo (P=0.002)

LS, least squares.

TMS confirms the clinical relevance of the change in TMC. TMS assesses all domains of motor dysfunction in HD, including chorea, dystonia, initiation of voluntary movement (dysarthria, tongue protrusion, finger tapping, hand pronation, and supination of hands), gait, and balance.2

AUSTEDO reduced disability and improved physical function2

FIRST-HD: SF-36 Physical Functioning Score (N=90, ITT)

SF-36 physical functioning scale score in FIRST-HD (N=90, ITT), significant 4.3-point mean difference vs placebo (P=0.03). SF-36 physical functioning scale score in FIRST-HD (N=90, ITT), significant 4.3-point mean difference vs placebo (P=0.03).

Patients on AUSTEDO reported being better able to perform daily activities2,5

The physical functioning portion of the SF-36 assesses patients’ reported ability to perform routine physical activities, such as:
  • Dressing
  • Bathing
  • Lifting/carrying
    groceries
  • Walking
  • Moderate to
    vigorous activities
  • Climbing stairs
  • Bending, kneeling,
    or stooping
  • Patients taking AUSTEDO achieved greater improvement in the SF-36 Physical Functioning Score at 12 weeks vs placebo (0.74 vs -3.61) 2

Treatment success recognized by both physicians and patients1

The first and only therapy to have more physicians and patients who rated overall HD chorea symptoms as “much improved” or “very much improved” as measured by CGIC and PGIC

FIRST-HD: Global Impression of Change at the End of Treatment for AUSTEDO Compared to Placebo (N=90, ITT)2,3

FIRST-HD: Global Impression of Change (GIC): Overall HD symptoms rated as "much improved" or "very much improved" at Week 12 (secondary endpoint), 42% of physicians observed treatment success (P=0.002), 51% of patients observed treatment success (P=0.002). FIRST-HD: Global Impression of Change (GIC): Overall HD symptoms rated as "much improved" or "very much improved" at Week 12 (secondary endpoint), 42% of physicians observed treatment success (P=0.002), 51% of patients observed treatment success (P=0.002).

Treatment success was defined as “much improved” or “very much improved” at Week 12.2

CGIC and PGIC are single-item questionnaires that ask the patient and physician to assess overall HD symptoms on a 7-point scale—from “very much worse”(-3) to “very much improved”(+3). Treatment success was defined as “much improved” or “very much improved” at Week 12.2

  • “Minimally improved,” defined as slightly better functioning from baseline, answers were also observed but not included in this measure
  • Patients whose status at Week 12 was not known were not included in this measure
PGIC and CGIC measurements

The PGIC is a patient-centered endpoint that is determined by how patients answered the question: “With respect to your overall Huntington's disease symptoms, how would you describe yourself now compared to immediately before starting study medication?” Only those patients who stated they were “much improved” or “very much improved” were considered to have treatment success. The CGIC assessed the change in HD chorea symptoms the same way, but used the HCP’s perspective.2,3

FIRST-HD study design

FIRST-HD was a randomized, 12-week, placebo-controlled study in patients with chorea associated with HD. Patients were randomized to receive AUSTEDO (n=45) or placebo (n=45). The mean age of patients taking AUSTEDO was 55.4 years (vs 52.1 years with placebo). 62% of patients on AUSTEDO were concomitantly taking antidepressants (vs 53% with placebo). The mean dose of AUSTEDO taken by patients at the end of the titration period was 40 mg/day. The primary efficacy endpoint was the treatment effect of AUSTEDO vs placebo, as measured by the TMC score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS), from baseline to maintenance. On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28. The combined group mean TMC score at baseline was 12.7.1-3

ARC-HD long-term, open-label extension study design

ARC-HD was an open-label, single-arm, 2-cohort study of long-term use of AUSTEDO in patients with HD chorea. The Rollover cohort had successfully completed FIRST-HD and underwent a 1-week washout prior to initiating 6 mg of AUSTEDO daily. The Switch cohort comprised patients with HD chorea who had been on a stable dose of tetrabenazine and were converted overnight to a dose of deutetrabenazine predicted to provide comparable systemic exposure. A total of 119 patients with HD chorea were enrolled (Rollover cohort, n=82; Switch cohort, n=37). In both cohorts, dosage was titrated by 6 mg/day per week. Endpoints were changes in the UHDRS, TMS, and TMC scores from baseline to Week 8, as well as those from Week 8 to Week 132 (or end of treatment).3

HD, Huntington's disease; SF-36, Short Form (36) Health Survey.

REFERENCES: 1. AUSTEDO® (deutetrabenazine) tablets current Prescribing Information. Parsippany, NJ, Teva Neuroscience, Inc. 2. Data on file. Parsippany, NJ: Teva Neuroscience, Inc. 3. Frank S, Testa CM, Stamler D, et al.; Huntington Study Group. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316(1):40-50. 4. Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology. 1988;38:391-394. 5. RAND Corporation. 36-Item Short Form Survey Instrument (SF-36). RAND Corporation. Accessed September 30, 2021. https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/survey-instrument.html