- Expects to announce topline data expected in the November/December timeframe.
- Enrolled patients had underlying medical conditions that are known risk factors for dementia that NE3107 has the potential to improve.
“Now that the last patient has completed the last treatment visit, our clinical team can begin the process leading to database lock,” stated Dr.
“We are cautiously optimistic about what to expect later this year based on data previously seen from our Phase 2 exploratory biomarker trial,” commented Cuong Do, BioVie’s President and CEO. “We do not need to show a reversal of cognitive decline as demonstrated in the Phase 2 trial for the current trial to be considered successful. If NE3107 demonstrates a slowing of cognitive decline equivalent to or better than the various monoclonal antibodies, we win because NE3107 is an oral agent that has been demonstrated to be safe in various trials thus far. Furthermore, we do not need to demonstrate efficacy and statistical significance across the board or with all the pre-specified subgroups such as mild- vs. moderate-AD, Aβ positive vs. negative, Hispanics vs. non-Hispanic, insulin-resistant vs. not, etc. A win in one or more subgroups is still a big win for the patient community and the company.”
The Company’s clinical monitors have started the process working with each clinical site to ensure that the electronic data capture (EDC) database properly reflects the assessments captured during the various clinical visits. This is the critical first step to creating and locking the database for analyzing the trial results and the eventual submission to the FDA for their review. The trial’s Statistical Analysis Plan (SAP) that pre-specifies the analyses and treatment populations and subgroups will be submitted to the FDA prior to locking the EDC.
About the NCT04669028 Trial
The NCT04669028 trial is a Phase 3, double-blind, randomized, placebo-controlled, parallel group, multicenter study of NE3107 in 316 to 400 patients who have mild- to moderate-AD and CDR 1-2 and MMSE 14-24. 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). The study was 80% powered with 316 patients, assuming a 20% drop-out rate. The Company chose to increase patient enrollment to over 400 after the trial started. Patients went through two weeks each of 5 mg and 10 mg BID dose titration followed by 26 weeks of 20 mg twice daily vs. placebo, randomized 1:1.
At baseline, the majority of the study population are coded with abdominal obesity (85%), hypertension (61%), and impaired glucose metabolism (IFG/T2D; 52%). Almost half of all patients (47%) are coded as having some degree of insulin resistance, 40% and 30% of patients are coded as having hypertriglyceridemia and hypercholesterolemia, respectively; and patients are coded as having elevated inflammatory markers. Since these are known dementia risk factors, we believe NE3107’s potential ability to help patients improve on some of these factors, as shown in some prior clinical trials, suggests that it may help patients improve on cognitive metrics in this trial.
Both Aβ+ and Aβ− patients with dementia were enrolled in the study and had, at baseline, comparable CDR-SB scores indicative of mild dementia. At baseline, enrolled Aβ+ patients had worse ADAS-Cog12 and MMSE scores (indicating lower cognitive functioning), while the enrolled Aβ− patients had significantly higher inflammation, insulin resistance, IFG, and hypertension, compared to their Aβ+ counterparts.
Subgroup analysis reveal higher degrees of impaired glucose metabolism and insulin resistance among the APOE ε4− patients compared to their APOE ε4+ counterparts and comparable baseline MMSE scores, indicating that both groups had mild to moderate cognitive impairment. Investigators in this study concluded that in the absence of classical risk markers, such as Aβ+ and APOE ε4+, central obesity (high waist-to-hip ratio) and age-related systems dysregulation, involving inflammation (elevated CRP, RANTES, and C1q), hyperglycemia, insulin resistance, dyslipidemia, and hypertension, may contribute to probable AD and disease progression.
Prior clinical results indicate that NE3107 may be capable of reducing inflammation in a manner that was in some cases significantly correlated with observed improvements in cognition. Specifically, in
Table 1. Baseline Characteristics
Characteristic | All | Aβ+a | Aβ−b | P | APOE ε4+ | APOE ε4− | P |
N=378 | n=57 | n=77 | n=97 | n=259 | |||
Age, mean (SE) y | 73 (0.3) | 76 (0.8) | 72 (0.6) | ** | 73 (0.6) | 73 (0.4) | - |
Female, % | 55 | 53 | 67 | - | 64 | 64 | - |
High WHRc, % | 85 | 84 | 84 | - | 81 | 82 | - |
FPG, mean, mg/dL | 112 | 100 | 112 | * | 106 | 115 | * |
IFG, % | 32 | 18 | 35 | # | 25 | 36 | - |
T2D, % | 20 | 14 | 22 | - | 17 | 25 | |
Fasting insulin, mean (SE), µlU/mL | 16 (1.1) | 10 (1.0) | 15 (2.4) | * | 12 (1.1) | 17 (1.6) | * |
High (>23), % | 15 | 9 | 15 | - | 10 | 17 | - |
HOMA2-IR, mean (SE) | 1.8 (0.1) | 1.3 (0.2) | 1.9 (0.2) | * | 1.5 (0.1) | 1.9 (0.1) | * |
1.4-2.5, % | 27 | 13 | 29 | ## | 24 | 27 | - |
>2.5, % | 20 | 15 | 21 | - | 15 | 22 | - |
MAGE, mean (SE), mg/dL | 70 (2.5) | 62 (3.4) | 68 (4.6) | - | 68 (4.2) | 71 (3.1) | - |
CRP, mean (SE), mg/L | 4.1 (0.4) | 1.8 (0.2) | 6.3 (1.2) | ** | 3.6 (0.8) | 4.3 (0.4) | - |
>3, % | 67 | 13 | 28 | # | 20 | 32 | |
>10, % | 18 | 0 | 18 | ## | 4 | 21 | |
C1q, mean (SE), mg/dL | 22 (0.2) | 21 (0.4) | 44 (0.5) | - | 21 (0.3) | 22 (0.2) | - |
High (>22), % | 32 | 28 | 33 | - | 34 | 31 | - |
RANTES, mean (SE), pg/mL | 28 (1.6) | 23 (2.0) | 33 (2.8) | ** | 26 (2.8) | 29 (2.0) | - |
Cholesterol, | |||||||
mean (SE), mg/dL | 189 (4) | 174 (5) | 175 (5) | - | 183 (4) | 180 (3) | - |
High (>199), % | 30 | 22 | 26 | - | 30 | 30 | - |
Triglycerides, | |||||||
mean (SE), mg/dL | 143 (4) | 130 (9) | 143 (8) | - | 132 (5) | 148 (5) | - |
High (>149), % | 40 | 27 | 36 | - | 36 | 41 | - |
High BP (>130/80), % | 61 | 47 | 71 | ## | 54 | 63 | - |
Low BP (<66 diastolic), % | 13 | 12 | 2.5 | ## | 15 | 4.1 | ## |
CDR-SB, mean (SE) | 6.3 (0.1) | 6.6 (0.3) | 6.2 (0.2) | - | 6.6 (0.2) | 6.1 (0.1) | ** |
MMSE, mean (SE) | 20 (0.1) | 20 (0.1) | 21 (0.2) | ** | 20 (0.2) | 20 (0.1) | - |
ADAS-Cog12, | 28 (0.4) | 31 (1.4) | 25 (0.7) | ** | 30 (0.9) | 27 (0.5) | ** |
mean (SE) | |||||||
ADCS-ADL, mean (SE) | 55 (0.6) | 57 (1.4) | 57 (1.2) | - | 56 (1.0) | 55 (0.5) | - |
Aβ42/40 ratio, | 0.095 | 0.085 (0.001) | 0.107 (0.001) | ** | 0.089 | 0.098 | ** |
mean (SE) | (0.001) | (0.002) | (0.001) | ||||
aPositive Precivity test; bNegative Precivity test; cFor females WHR>0.8 and for males WHR>0.95; Mann-Whitney *P <0.05, **P<0.01; Fisher’s Exact Test #<0.05, ## <0.01. | |||||||
About NE3107
NE3107 is an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds extracellular signal-regulated kinase. BioVie’s Phase 3 trial is the largest study to date to evaluate the safety and efficacy of NE3107 in patients with AD. NE3107 is the only anti-inflammatory agent currently in phase 3 development for AD. Consistent with the proposed anti-inflammatory and insulin-sensitizing properties of NE3107, this phase 3 study was designed to confirm the efficacy and safety of NE3107 treatment in patients with probable AD.
About BioVie
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the Company’s strategy, plans and objectives, such as statements regarding the Company’s anticipated timeline for announcing results from the NE3107 Phase 3 potential pivotal trials. Forward-looking statements may generally be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although
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