ProMIS reports no ARIA-E in blinded six-month Alzheimer's trial update

ProMIS Neurosciences (Nasdaq: PMN) reported blinded six-month interim safety and biomarker data from its Phase Ib Alzheimer's disease trial, with no cases of amyloid-related imaging abnormalities-edema (ARIA-E) observed across any genotype, including APOE4 homozygotes—a population at highest risk of treatment-related ARIA with currently approved anti-amyloid therapies.

The PRECISE-AD trial is evaluating PMN310, a humanized IgG1 monoclonal antibody that, unlike plaque-binding antibodies, is designed to bind soluble amyloid-β oligomers, which are thought to be among the most neurotoxic forms of amyloid while potentially avoiding interactions with vascular amyloid associated with ARIA.

In the blinded interim analysis of 136 patients, total ARIA was reported at 4.4%, consisting entirely of mild, asymptomatic ARIA-H microhemorrhages, with no treatment-related serious adverse events and no drug-related discontinuations. The trial enrolled 144 participants across three intravenous dosing cohorts of 5, 10, and 20 mg/kg, with a 3:1 active-to-placebo randomization, and remains blinded.

On biomarkers, 68.5% of patients showed a decline from baseline in plasma pTau217 and 62.5% showed a decline in CSF MTBR-tau243, against expected increases based on natural-history trajectories. The company noted these directional trends are consistent with the trial's randomization pattern and potential target engagement, but explicitly stated the observations are not a determination of efficacy and may not ultimately reflect clinical effects. Treatment allocations remain unknown. Unblinded 12-month topline data, including efficacy endpoints, are expected in Q1 2027.

The ARIA profile reported here stands in contrast to those of the two FDA-approved amyloid-directed therapies. Lecanemab (Leqembi), developed by Eisai and Biogen, produced total ARIA in 21.3% of patients in the Phase III CLARITY AD trial, including 12.6% ARIA-E. Donanemab (Kisunla), developed by Eli Lilly, produced total ARIA in 36.8% of patients in TRAILBLAZER-ALZ 2, including 24.0% ARIA-E. Both agents carry prescribing limitations for APOE4 homozygotes due to elevated ARIA risk in that genotype; the PRECISE-AD interim reported no ARIA-E in any genotype in a population that included 61% APOE4 carriers, of which 11% were homozygotes. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.

PMN310 received FDA Fast Track Designation in July 2025. The Phase Ia healthy volunteer study that preceded PRECISE-AD has completed enrollment. The forthcoming unblinded 12-month analysis will determine whether the favorable interim safety profile is accompanied by biomarker and clinical efficacy benefits.

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