Patients treated in the 10- and 20-mg once daily groups showed statistically significant improvements in UPDRS parts II, III, IV, and in total MDS-UPDRS scores compared with baseline.
Recently announced results from the phase 2 dosing trial (NCT045243351) of ANVS401 (Annovis Bio) showed that the investigational agent was well-tolerated and was superior to placebo on improving motor function in patients with Parkinson disease (PD).1
A total of 54 patients with PD were recruited in the analysis, an increase from the original cohort which had 14 patients with Alzheimer disease (AD) and 14 with PD. Patients were treated with 0 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 80 mg of ANVS401 once daily and were assessed on neuropsychiatric measures, such as the coding test of the Wechsler Adult Intelligence Scale (WAIS) and the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).
Patients completed the assessments at day 0 and day 25. At the conclusion of the study, those in the 5-mg, 20-mg, and 80-mg once-daily groups had statistically significant improvements in WAIS coding scores compared with those on placebo and from baseline scores, indicating increased motor dexterity, as well as speed and accuracy. Statistically significant improvements were also observed in the UPDRS part II, III, and IV sections, as well as total MDS-UPDRS test for those treated in the 10-mg and 20-mg once-daily groups. Investigators concluded that the drug shows better efficacy around 10 mg to 20 mg and will thus provide guidance for the doses used in the upcoming phase 3 studies of patients with AD and PD.
"We are thrilled by these improvements in motor function of PD patients. Through examination of this dose-response, we can determine an optimal safe and efficacious dose as we move forward towards initiation of Phase 3 clinical trials with much larger patient populations and longer timelines. These positive efficacy results, which expand on our previous data from AD and PD patients, add clarity to the benefits that ANVS401 may offer to patients suffering from these chronic neurodegenerative diseases," Maria L. Maccecchini, PhD, founder, president, and chief executive officer, Annovis, said in a statement.1 "We are still analyzing certain biomarker data from the 54 PD patients and will share the results when they are available. We will be asking the FDA for a meeting to receive guidance on next steps in clinical development in light of the AD/PD Phase 2 clinical results."
The company has released data from this study before, beginning in March, when interim results showed that treatment with ANVS401 improved patients’ speed and coordination scores, with no serious adverse events. While almost statistically significant (P = .07), the treated group had the same number of complications before and after 1 month of treatment, suggesting they were stable, while the placebo group had more complications, suggesting a worsening.2
Annovis followed up those results with more data in May, which showed that ANVS401 statistically improved cognition as measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 11 (ADAS-Cog11). From baseline to 25 days, ADAS-Cog11 scores increased by 4.4 points, correlating to a 30% improvement (P = .04). When compared with placebo, the investigational drug showed improvement of 3.3 points, or 22% (P = .13).3
In July, Annovis put out a statement claiming they were happy with the interim results to date. At the time, they also released additional data, including that all the neurotoxic proteins were reduced in patients with AD, with some reductions statistically significant and some not. Additionally, neurofilament light was reduced in both patients with AD and PD compared to placebo, although the results were not statistically significant. All the inflammatory markers showed statistically significant reductions after the 25-day treatment period in 14 patients with PD. Lastly, investigators determined that there was a statistically significant increase in the ratio of amyloid-ß 42 (Aß42) and Aß40 among patients with AD.4