Objective: To measure functional decline by TFC change in HD patients treated with open-label pridopidine at 45 mg BID (Open-HART) for 36 months (mos), and compare with matched historical placebo cohorts in long-duration HD studies of coenzyme Q10 (CARE-HD and 2CARE).

Background: HD patients experience motor, cognitive, and behavioral symptoms that lead to long-term functional decline. TFC (range 0–13, higher scores indicate greater capacity) is the most accepted measure of overall function in HD and most sensitive to early changes in disability.

Methods: Open-HART patients taking pridopidine and placebo cohorts of CARE-HD and 2CARE were matched for baseline (BL) TFC, total motor score, age, gender, and years since diagnosis. Patients were then matched on CAG repeat length. TFC at BL and up to 36 mos was analyzed. Repeated measures model compared change from BL for Open-HART and placebo cohorts separately at 12, 24 or 25, and 30 or 36 mos (based on data availability).

Results: BL mean(SD) TFC in Open-HART (n=31) was 10.6(1.5). TFC for matched placebo cohorts in CARE-HD (n=18) and 2CARE (n=30) were 10.4(1.8) and 10.8(1.3), respectively. Mean change from BL in TFC at 12, 24, and 36 mos for the Open-HART cohort matched to 2CARE was –0.8(1.7); –1.3(2.1), –1.9(2.3) and for 2CARE was –1.4(1.7), –2.4(2.1), and –2.8(1.9), respectively. Mean change at 12, 24, and 36 mos for the Open-HART cohort matched to CARE-HD was -0.8(2.2), -1.2(2.3), -1.8(2.3) and for CARE-HD at 12, 25, and 30 mos was –0.9(1.6), –2.4(1.7), –3.1(1.9). Matched Open-HART cohort had significantly slower decline than 2CARE at 24 (P=0.02) and CARE-HD at 30 mos (P=0.04). When additionally matched for CAG repeat length, mean changes in TFC from BL at 12, 24, and 36 mos also showed modest decline over time (matched to 2CARE –0.3(1.6), –0.8(2.0), –0.9(1.9) and matched to CARE-HD –0.2(1.6), –0.5(1.9), –1.2(1.9), respectively).

Conclusions: This exploratory analysis suggests slower functional decline as measured by TFC for pridopidine-treated HD patients compared with matched placebo subjects from other studies. Results are consistent with data from the Pride-HD study showing slower functional decline as measured by TFC. Limitations should be considered when interpreting results. A Phase III trial to confirm findings on functional decline is planned.

Presented at: AAN; April 22–28, 2017; Boston, MA, USA

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-pridopidine-on-total-functional-capacity-tfc-in-huntington-disease-hd-results-of-a-cohort-comparison-of-open-hart-and-historical-placebo-subjects/