BioVie Inc (NASDAQ:BIVI) said its NM101 trial evaluating NE3107 in the treatment of patients with Alzheimer’s Disease has achieved its revised enrollment target of 400 patients, with top-line results from the study expected to be announced in October 2023.
The company noted that the NM101 trial is a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate NE3107 in patients who have mild to moderate Alzheimer's disease (NCT04669028).
The study has co-primary endpoints looking at cognition using the Alzheimer’s Disease Assessment Scale-Cognitive Scale (ADAS-Cog 12) and function using the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), it added.
READ: BioVie updates investors on its Alzheimer’s and Parkinson’s clinical programs
“We look forward to having topline data from this trial in October,” BioVie president and CEO Cuong Do said in a statement. “We are optimistic that this trial will provide similar data to what was seen in the Phase 2 exploratory study, which showed that patients treated with NE3107 experienced enhanced cognition as measured by multiple assessment tools, including a 2.1 points improvement on the modified ADAS-Cog12 scale.”
BioVie noted that the NM101 trial protocol originally specified enrolling at least 316 patients equally randomized to treatment and placebo arms.
The protocol also pre-specified the potential for a review by the data safety monitoring board (DSMB), in a manner that is blinded to the company, when roughly 50% of the 316 enrolled patients have completed the study to determine if increasing enrollment of up to 400 patients might be desirable for enhancing the probability of achieving statistical significance.
Due to an accelerating pace of enrollment as the trial progressed, the company said it enrolled 316 patients before 50% of enrolled patients had completed the study. Consequently, it decided to proceed to 400 patients without the pre-specified interim analysis.
About inflammation and NE3107’s mechanism of action
BioVie said neuroinflammation, insulin resistance, and oxidative stress are common features in the major neurodegenerative diseases, including Alzheimer’s Disease, Parkinson’s Disease, frontotemporal lobar dementia, and amyotrophic lateral sclerosis (ALS).
NE3107 is an oral small molecule, blood-brain permeable, compound with potential anti-inflammatory, insulin-sensitizing, and ERK-binding properties that may allow it to selectively inhibit ERK-, NFκB- and TNF-stimulated inflammation. NE3107’s potential to inhibit neuroinflammation and insulin resistance forms the basis for the company’s work testing the molecule in AD and PD patients.
Remarkable parallels exist between Alzheimer’s Disease and Parkinson’s Disease, among them activated microglia driving inflammation, involvement of TNFα, oxidative stress, protein misfolding, mitochondrial dysfunction, and insulin resistance.
In preclinical and clinical studies, BioVie said NE3107 reduced inflammation and enhanced insulin sensitivity, both of which are important to Parkinson’s Disease pathology.
Preclinical studies in marmoset monkeys have shown NE3107 administered alone to be as pro-motoric as levodopa, underscoring the apparently critical role of inflammation in the expression of Parkinson’s Disease dysmobility. When NE3107 was administered with levodopa, the combination improved motor control better than either drug alone.
Furthermore, in the marmoset study, NE3107 reduced the severity of levodopa-induced dyskinesia (LID) concurrent with pro-motoric benefit and decreased neurodegeneration, preserving twice as many dopaminergic neurons compared to control.
BioVie is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease.
Contact the author at stephen.gunnion@proactiveinvestors.com