J010 Integrated efficacy analysis of four randomized placebo-controlled trials supports pridopidine’s significant and consistent treatment benefits across key clinical measures of Huntington’s disease

<h3>Background</h3> In PROOF-HD, pridopidine improved key measures of HD clinical progression (cUHDRS), function (TFC), cognition (SWR), and motor (Q-Motor). <h3>Aim</h3> To determine if results from prior HD studies with pridopidine are consistent with PROOF-HD. <h3>Methods</h3> An analysis was performed on 435 participants off antidopaminergic medications (ADMs) (placebo n=227; pridopidine n=208) from four randomized, double-blind, placebo-controlled trials (HART, MermaiHD, PRIDE-HD and PROOF-HD) assessing pridopidine (45mg bid) in early HD patients (TFC≥7). <h3>Results</h3> Pridopidine showed robust improvement vs placebo in TFC through week 78, reaching nominal significance at weeks 26 (Δ0.31, p=0.03), 39 (Δ0.43, p=0.01), 52 (Δ0.38, p=0.02), and 78 (Δ0.49, p=0.02). As PRIDE-HD did not measure SWR, cUHDRS is unavailable; therefore, a revised cUHDRS excluding SWR was used. Pridopidine shows meaningful benefits in cUHDRS^(-SWR) through week 78, reaching nominal significance at weeks 26 (Δ0.30, p=0.006), 39 (Δ0.45, p=0.002), and 52 (Δ0.29, p=0.04). All of the trials contribute positively to the observed benefits. Pridopidine improves all measures of Q-Motor Finger Tapping (FT) and Pronation Supination (Pro_Sup) through week 78. These include improvements from baseline in FT through week 52, with nominal significant benefits at weeks 12 (Δ-31msec, p=0.046), 26 (Δ-27msec, p&lt;0.001), 52 (Δ-25msec, p=0.02), and 78 (Δ-25msec, p=0.05). Similar benefits are seen for Pro_Sup. In additional analyses of subjects on low dose ADMs, as per the regulatory label when used in the presence of a CYP2D6 inhibitor such as pridopidine, the positive effects of pridopidine are maintained. <h3>Conclusion</h3> This pooled analysis supports and validates PROOF-HD findings of consistent, sustained, and clinically meaningful benefits of pridopidine in HD.