BioVie Inc (NASDAQ:BIVI) has announced positive results from two Phase 2 trials assessing NE3107’s potential in Parkinson’s Disease (PD) and Alzheimer’s Disease (AD).
The NM201 study (NCT05083260) is a double-blind, placebo-controlled, safety, tolerability, and pharmacokinetics study in Parkinson's disease (PD) participants treated with carbidopa/levodopa and NE3107. In the study, 45 patients with a defined L-dopa 'off state' were randomized 1:1 to placebo: NE3107 20 mg twice daily for 28 days.
The trial was launched with two design objectives: 1) the primary objectives are safety and a drug-drug interaction study as requested by the US Food & Drug Administration (FDA) to demonstrate the absence of adverse interactions of NE3107 with levodopa; and 2) the secondary objective is to determine if preclinical indications of promotoric activity and apparent enhancement of levodopa activity can be seen in humans. Both objectives were met, the company noted.
WATCH: BioVie Pharma Inc announces NE3107 Phase 2 trial has been fully enrolled
“NE3107 shows promise, and if the current findings are confirmed, it may represent one of the most significant advances in Parkinson’s treatment in decades,” said Joseph Palumbo, BioVie’s chief medical officer in a statement.
“The NE3107-levodopa combination’s ability to provide 3+ points improvement on the part 3 score compared to levodopa-alone is a very meaningful clinical benefit according to PD experts. It may be more beneficial for patients whose disease is less advanced as seen from the 6+ point superiority on the part 3 score for patients <70 years old," he added.
Before study commencement and at multiple points throughout the 28-day trial, patients who did not receive PD medications for at least 8 hours overnight were observed using the Unified Parkinson’s Disease Rating Scale (UPDRS) first thing in morning (hour 0). Patients were then given medication and observed again using UPDRS at 1, 2, 3, 4, and 8 hours after drug administration. Part 3 of the UPDRS instrument assessed motor control.
Patients treated with NE3107 and levodopa saw improvements of part 3 score on Day 28 compared to Day 0 that is 3+ points better than those treated with levodopa alone at the 2- and 3-hour marks. This level of superiority is considered by PD experts to be clinically meaningful. Patients younger than 70 years old treated with NE3107 and levodopa experienced improvements that are roughly 6 points better than levodopa-treated alone. Patients younger than 70 years old represented roughly one-half of study participants.
After 28 days of treatment, 63.6% of patients treated with levodopa alone experienced >30% improvement from Day 0 at the two-hour mark compared to 80% for NE3107+levodopa-treated patients and 88.9% of NE3107+levodopa patients under 70 years old. The pattern was also observed for other time periods. There were no drug-related adverse events
BioVie said full details from this trial will be presented at the upcoming AD/PD 2023 International Conference on Alzheimer’s and Parkinson’s Diseases to be held March 28-April 1, 2023 in Gothenburg, Sweden.
“This trial is primarily a safety and drug-drug interaction study that we expanded in hopes of finding an efficacy signal,” noted Cuong Do, BioVie’s president and CEO. “The fact that this small trial showed this magnitude of therapeutic impact for NE3107 allows us to proceed with planning the Phase 3 program for discussion with the FDA.”
“My review of the BioVie study of NE3107 in Parkinson’s Disease suggests that there is a probable signal of clinical efficacy in the treatment of motor symptoms,” added Dr Douglas Felter, a former executive at Pfizer, AbbVie, and AveXis experienced in developing PD treatments who was not associated with the NM201 trial. “This signal should be pursued in a larger, focused, confirmatory study.”
Additional Findings from Phase 2 Alzheimer's Disease Trial
In a second statement, BioVie reported encouraging data suggesting that NE3107 has an impact on improving patients’ DNA methylation profiles, potentially impacting biomakers of aging-related disease states.
The company said the Phase 2 Investigator-Sponsored Trial (NCT05227820) enrolled a total of 23 patients with an average age of 71.1 years in an open-label, single-arm study to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Alzheimer’s Disease (AD) and inflammation that can be measured in cerebral spinal fluid, blood samples, and functional magnetic resonance imaging in patients before and after treatment with 20 mg of NE3107 twice daily for three months.
Dr Sheldon Jordan, the principal investigator, and his team presented detailed data through posters and a platform presentation at the Clinical Trial in Alzheimer’s Disease (CTAD) annual conference, held in San Francisco, California, that ended December 2, 2022. These data showed the following among patients with MMSE>=20 (i.e., mild cognitive impairment and mild AD):
NE3107 showed the potential to enhance cognition as measured by multiple assessment tools, including a 2.2 point improvement (p=0.0173) on the modified ADAS-Cog12 scale equating to a 21.1% (p=0.0079) change compared to baseline, a 0.11 point improvement (p=0.0416) on the Clinical Dementia Rating scale (CDR), equating to 19.4% (p=0.0416) change from baseline, and a 0.07 point improvement in the ADCOMS scale, equating to 27.4% improvement (p=0.009).
NE3107 reduced CSF phospho-tau levels by -1.66 pg/mL (p=0.0343) and the ratio of p-tau to A42 by -0.0024 (p=0.0401). 18 of 22 patients with abnormal baseline scans showed improvement in one or more brain regions as seen from advanced functional MRI studies. No drug-related adverse events were observed.
Blood samples were taken from the patients who participated in the Alzheimer’s Phase 2 trial before and after three months of treatment with NE3107, and these samples were analyzed to assess NE3107’s potential to reduce inflammation and alter DNA methylation associated with epigenetic biological clocks.
The resulting data for patients treated with NE3107 for three months showed a reduction of 3.3 years (p=0.0021) on the Horvath DNA methylation SkinBlood clock. Furthermore, 19 out of the 22 patients experienced this reduction in the SkinBlood clock score.
The finding that NE3107 affects the SkinBlood clock provides an impetus to explore further the relationship between NE3107 improving neurodegeneration and other inflammation-driven diseases.
“This additional finding from study of NE3107 in the treatment of dementia reflects a hypothesis-driven effort to investigate the effect of epigenetic change associated with an anti-inflammatory compound, as inflammation is hypothesized to drive both neurodegeneration and aging,” said Dr Jordan. “The study was designed to decrease inflammation and measure the effect using the epigenetic clocks. I am collaborating with Dr Horvath’s team on this effort since they are the recognized leaders in the field.”
“We are very excited by this initial finding and recognize that there is still much more to learn about NE3107’s impact on the biomarkers of aging-related disease states and how this may affect disease progression,” commented Cuong Do, BioVie’s president and CEO. “We look forward to working with collaborators to answer questions such as whether the reversal will accumulate with longer treatment duration, the durability of the effect, and whether this translates to a reduced risk in diseases associated with aging.”
BioVie is a clinical-stage company developing innovative therapies to overcome unmet medical needs in chronic debilitating conditions. In neurodegenerative disease, the company’s drug candidate NE3107 inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases.
Contact the author at jon.hopkins@proactiveinvestors.com