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Alzheimer’s Drug Fails to Meet Primary Endpoints in Phase 3 Trial But Shows Benefit in Monotherapy Subgroup
A phase 3 study of LMTX (TauRx Therapeutics), an investigational tau aggregation inhibitor, has failed to meet its coprimary endpoints in patients with mild or moderate Alzheimer’s disease (AD). However, significant reductions in the rate of disease progression were observed across three key measures in patients who were treated with LMTX as their only AD medication. Paradoxically, the same efficacy findings were not seen in patients who received LMTX in combination with other standard AD treatments.
The three measures showing improvement included the Alzheimer’s Disease Assessment Scale–Cognitive (ADAS-Cog); the Alzheimer’s Disease Co-operative Study–Activities of Daily Living (ADCS-ADL) inventory; and an assessment of the level of brain atrophy (lateral ventricular volume [LVV], as measured by magnetic resonance imaging [MRI]).
The 15-month, randomized, double-blind, placebo-controlled trial compared LMTX with placebo in 891 subjects with mild or moderate AD.
The ADAS-cog decline analysis produced significant treatment effects of –6.3 (P < 0.0001) and –5.8 (P < 0.0001) units after patients received 75 mg twice daily (BID) or 125 mg BID of LMTX as monotherapy, respectively, while the ADCS-ADL decline analysis produced significant treatment effects of 6.5 (P = 0.0013) and 6.9 (P = 0.0007) after treatment with 75 mg BID or 125 mg BID of LMTX as monotherapy, respectively.
LMTX monotherapy also slowed the rate of progression of brain atrophy, as measured by the LVV derived from MRI scans. Expansion of the LVV was reduced by 38% (P = 0.0023) and 33% (P = 0.0014) for 75 mg BID and 125 mg BID of LMTX, respectively, compared with the control in these patients. These reductions in LVV expansion were confirmed by corresponding increases in whole-brain volumes in the same patient groups.
In patients receiving LMTX as add-on therapy to current AD medications, there were no statistically significant differences in ADAS-cog, ADCS-ADL, or LVV measurements among the control, LMTX 75 mg BID, and LMTX 125 mg BID treatment groups.
Tau aggregation inhibitors work by undoing the tau tangles that cause dementia, thereby slowing or arresting memory loss.
Source: TauRx Therapeutics; July 27, 2016.