Efficacy data is announced from phase III trial of NE 3107 in patients with mild to moderate Alzheimer's disease

Data from evaluable patients show NE 3107’s treatment advantage compared to placebo may be equal to or greater than the benefit from approved AD monoclonal antibodies. NE 3107-treated patients also experienced a 4.66-year advantage in age deceleration vs. placebo as measured by epigenetics/DNA methylation Skin Blood Clock.

The trial started during the COVID-19 pandemic when access to clinical sites was limited and enrolled a total of 439 patients through 39 sites. Upon trial completion, the Company found significant deviation from protocol and Good Clinical Practice (GCP) violations at 15 sites (virtually all of which were from one geographic area). This highly unusual level of suspected improprieties led the Company to exclude all patients from these sites and to refer them to the FDA Office of Scientific Investigations (OSI) for further action. After these exclusions, 81 patients remained in our Modified Intent to Treat (MITT) population, 57 of whom were in the Per-Protocol population which included those who completed the trial and were verified to take study drug from pharmacokinetic (PK) data.

“These data show NE 3107’s treatment advantage over placebo to potentially be equal to or greater than data reported from clinical trials for the approved medications for AD without the associated safety concerns,” said Cuong Do, BioVie’s President and CEO. “The adaptive trial design gives us the flexibility to continue patient enrollment in the advancement of this potentially important treatment for AD, and we look forward to discussing our findings of NE 3107’s magnitude of therapeutic impact with our potential partners. I am also very proud of the integrity our team displayed in taking immediate action to identify and report the potentially problematic sites to the FDA for independent investigation. Importantly, we recognize that along with the development of new and innovative therapeutics, our foremost responsibility in clinical testing is to protect the rights and well-being of study patients and the integrity of the clinical research process.”

Key Findings; Patients treated with NE 3107 showed improved performance compared to placebo on all cognitive and functional assessments commonly used in the prior approval of amyloid beta (Abeta)-based AD therapies, although the data missed statistically significance due to site exclusions. Placebo-treated patients significantly worsened on virtually all assessments as expected from natural history of the disease. By contrast, NE 3107-treated patients experienced a treatment advantage after 6 months that was equal to or greater than results reported from clinical trials for the approved Abeta monoclonal antibody treatments after 18 months.

Patients treated with NE 3107 saw an average of -5.66 years of age deceleration of the DNA methylation advantage compared to those on placebo. Age deceleration is the difference between the patient’s biological age as measured by the Horvath DNA methylation Skin Blood clock less the actual chronological age. NE 3107 is believed to be the first drug candidate to demonstrate this impact on DNA methylation and the aging process in a double-blinded, placebo-controlled clinical.

The unblinded topline efficacy data from 57 per-protocol participants reaffirmed what has been seen in previous studies of NE 3107 – which is that patients treated with this molecule appear to experience cognitive and functional improvements as measured by multiple assessment tools,” said Dr. Joseph Palumbo, Executive Vice President, R&D and Chief Medical Officer. “This data reinvigorates our ambition to further evaluate NE 3107 and bring the Alzheimer’s community a differentiated treatment that is safe and has a meaningful impact on cognition.”

“The unblinding of topline efficacy data from the trial confirmed an unusual pattern we saw with the blinded data – that patients in a particular demographic group within the trial seemed to have a data pattern different from historical evidence for this demographic group. Patients from this demographic group in this trial reportedly experienced cognitive improvements that were improbable scientifically, and inconsistent with the pathology of this disease,” stated Suzanne Hendrix, Founder & CEO of Pentara, a specialized biostatistics consulting firm that has assisted dozens of AD clinical trials. “When sensitivity analyses were performed, we determined that the anomalous demographic data were associated with the previously identified anomalous sites located in the same geographic area.”