On January 21, AriBio, a biopharmaceutical company based in South Korea, announced the completion of a Phase II clinical trial of AR1001, an oral biological therapy for the potential treatment of mild to moderate Alzheimer’s disease (AD). AR1001 is potent anti-amyloid with a novel mechanism of action that positioned it as a first-in-class drug in the AD treatment landscape. It is administrated orally, unlike most pipeline drugs of this class, which will have a positive impact on patient compliance. Given the complexity in discovering and developing disease-modifying treatments in this market, as well as the high rate of late-stage clinical trial failures, the advancement of AR1001 in trials signals little promise for patients and provides guidance for future AD trials.

AR1001 acts by inhibiting phosphodiesterase 5 protein, which is believed to have benefits against the accumulation of amyloid beta (Aβ) peptides, the main pathological hallmark of AD. AR1001 showed potential evidence of promoting neuronal cell survival in AD during early stage studies. As there are no approved treatments that can halt or slow down the progression of neurodegeneration in AD, AR1001 has an opportunity to meet this need if it proves to be effective and tolerable.

The double-blind, randomized, placebo-controlled trial assessed the efficacy and safety of AR1001 in a total of 210 patients over six months. Another six-month extension phase of the trial will further evaluate various dosing regimens on approximately 80% of the same patients who opted to participate in this phase. Although the preliminary results of this study are expected to be announced by the end of Q1 2021, the company indicated that the drug showed an excellent safety and tolerability profile and that patients had overall positive reactions throughout the study.

As such, the company is planning to initiate a global Phase III trial in 2022, which means that the drug filing in the US might be expected in Q1 2024 if it succeeds in both trials. This will be an uphill struggle for AR1001. Pipeline agents targeting Aβ have repeatedly failed in previous trials, which has led to suggestions to shift focus from the amyloid hypothesis to combination therapies. However, some have argued that anti-amyloid treatment should be only studied in the very early stages of AD, which seems to be the case in AR1001 Phase II trial.

Key opinion leaders interviewed by GlobalData did not believe there will ever be one product that can cure AD. Rather, they consistently noted that the future of AD treatment will likely entail a combinatory use of preventative, symptomatic, and disease-modifying products. Consequently, AriBio must overcome some common challenges in future trials regarding aspects of trial design, biomarkers, and targeting the optimal phase of the disease in AD patients.