NeurMedix, LLC, a San Diego based privately held clinical stage
pharmaceutical company announced that it has received authorization
from the U.S. Food and Drug Administration’s (FDA) Office of
Neuroscience, Division of Neurology I, to initiate a pivotal phase
3 clinical trial in Alzheimer’s disease with its lead clinical drug
candidate, NE3107, 17α-ethynyl-androst-5-ene-3,7,17-triol. NE3107
is a small molecule, orally administered, anti-inflammatory,
insulin-sensitizing agent with a novel mechanism of action. The
clinical trial, a Phase 3, randomized, double-blind,
placebo-controlled, parallel group, multicenter study of NE3107 in
subjects who have mild to moderate Alzheimer’s disease
(NCT04669028) will be conducted at approximately thirty clinical
sites in the U.S.
The trial will evaluate twice daily 20 mg oral
NE3107 versus placebo for 30 weeks beginning with dose titration of
5 mg BID in weeks 1 and 2 and 10 mg BID in weeks 3-4, with 20 mg
BID for weeks 5-30. Approximately 316 patients will be randomized
with a 1:1 ratio of active to placebo. Inclusion/exclusion criteria
are structured to help select only AD patients and exclude subjects
with cognitive impairment secondary to other medical conditions.
Stable regime of approved AD co-medication is permitted, and
continued use of glycemic control medications stable for three
months prior to randomization is permitted. The co-primary
endpoints are mean change from baseline to week 30 in ADAS-Cog 12
comparing the NE3107 group to the placebo group, and mean change
from baseline to week 30 in ADCS-CGIC comparing the NE3107 group to
the placebo group. Secondary endpoints include additional tests of
neuropsychological deficits, measures of glycemic control, and
inflammation.
The rationale for the trial is based on growing
scientific evidence linking inflammation and insulin resistance to
Alzheimer’s disease dementia and progression. The recently coined
term, “type 3 diabetes,” underscores the close link between
Alzheimer’s disease and insulin resistance that develops from
inflammatory inactivation of the insulin signaling pathway in the
brains of Alzheimer’s patients. Inflammation has long been known as
a major driver of Alzheimer’s disease, but currently approved
anti-inflammatory agents, and potentially those in development, are
poorly suited to chronic use in Alzheimer’s due to one or more
factors relating to poor blood-brain barrier penetration, toxicity
and side effects, or mechanisms of action that are too narrow to be
effective against the multiplicity of inflammatory pathways that
are activated in the disease. NE3107 addresses these issues as a
highly blood brain barrier permeable drug, with very low potential
for toxicity that targets the major inflammation signaling
pathways, those mediated by extracellular signal regulated kinase
(ERK), nuclear factor kappa-light-chain-enhancer of activated B
cells (NF-κB), and tumor necrosis factor (TNF). The company
believes that NE3107’s combination of small molecule
characteristics and broad mechanism of action without
immunosuppressive effects provides advantages over protein-based
TNF inhibiting therapies, as well as antibodies against amyloid
beta and phospho-tau.
Commenting on the announcement, Terren Peizer,
Chairman and CEO, and majority shareholder of NeurMedix and BioVie
Inc. (NASDAQ: BIVI), a clinical-stage company developing innovative
drug therapies for liver disease, stated, “It is well-known that
insulin resistance predicts neuroinflammation, and cognitive
decline, and that up to 81% of Alzheimer’s disease patients have
impaired glucose tolerance or type 2 diabetes (Diabetes 53 474
2004). We believe NE3107 reduces neuroinflammation and restores
insulin sensitivity, and thereby may halt the progression of
Alzheimer’s disease. Of the four indications that we hope to pursue
in the coming year, we believe that the application of NE3107 to
Alzheimer’s disease has a very high probability of success as it
uniquely addresses all of the known pathways of Alzheimer’s
disease. The FDA’s authorization of this pivotal phase 3 clinical
trial is an important milestone in our pursuit of a life changing,
safe, and efficacious intervention for this largest unmet medical
need. Having followed the evolution of the science, the drug
development, and capital investment in excess of $85 Million in
NE3107, it’s gratifying for the NeurMedix team to have the
opportunity to validate and deliver meaningful benefits to this
important patient population.”
Christopher Reading PhD, Chief Scientific
Officer of NeurMedix, added: “Inflammation-driven systems
dysregulation has been well-described in Parkinson’s and
Alzheimer’s diseases. It was recently reported in the journal
Diabetes Care that increases in coefficients of variation (CVs) of
fasting glucose and HbA1c were independently associated with an
increased risk of Alzheimer’s disease (Diabetes Care 40 1210 2017),
suggesting that our previous findings that NE3107 decreases system
dysregulation should bode well for the Phase 3 trial.”
The protocol was developed in collaboration with
a team from a leading global contract research organization (CRO),
Worldwide Clinical Trials (Worldwide), led by Dr. Michael Murphy,
MD, PhD, Worldwide’s Chief Medical and Scientific Officer. Dr.
Murphy is a widely recognized expert in translational research,
strategic program development, and facilitation of
commercialization during clinical development, with greater than 30
years of experience in Alzheimer's drug development and clinical
trial design. The trial will be managed by Cognitive Research
Corporation (CRC, St. Petersburg, FL), a full-service CRO with a
proven track record in assessing both the efficacy and safety of
products across a wide range of indications, and primarily focused
on CNS research in psychiatric and neurologic therapeutic areas.
NeurMedix expects to enroll the first patient in May 2021.
Previous clinical studies with NE3107 conducted
in the FDA Division of Metabolism and Endocrinology Products
demonstrated anti-inflammatory and insulin sensitizing activity in
subjects with evidence of systemic inflammation. Publication of
these results reported that NE3107 increased insulin-stimulated
glucose disposal and HDL cholesterol, and decreased C-reactive
protein (CRP, a measure of systemic inflammation) in impaired
glucose tolerance subjects (Obesity 21 E343 2013). A subsequent
publication summarized inflammatory, hematologic and metabolic
parameters from placebo-treated subjects with increasing metabolic
dysregulation included healthy volunteers, impaired glucose
tolerant subjects, dyslipidemia patients, metformin-treated and
treatment-naïve type 2 diabetes patients, and described the effects
of inflammation on metabolic and hematological homeostasis. The
publication reported that inflammation associated with increasing
metabolic dysregulation increased the CVs of clinical laboratory
tests for inflammatory, hematologic and metabolic parameters,
demonstrating inflammation-driven systems dysregulation. In the
type 2 diabetes study, advanced type 2 diabetic subjects on placebo
showed statistically random effects for erythroid, glucose and
HbA1c fluctuations. After 84 days of NE3107 treatment, NE3107
significantly decreased insulin resistance, postprandial glucose
and HbA1c in obese, inflamed patients. In addition, NE3107
significantly decreased variances in tests for hyperglycemia
(fasting glucose, fructosamine), erythroid (HbA1c), dyslipidemia
(triglycerides), endocrine (insulin, leptin), inflammatory
(monocyte chemoattractant protein-1 [MCP-1]), and homeostasis
(homeostatic model assessment of pancreatic beta cell function
[HOMA %B] and insulin resistance [HOMA IR]) parameters, compared to
placebo (Mediators Inflamm 2013 814989). The conclusion being that
the anti-inflammatory action of NE3107 restored homeostasis to the
dysregulated parameters.
About NeurMedix, LLC
NeurMedix, Inc. is a clinical-stage
biopharmaceutical company that engages in developing products for
the treatment of neurological and neuro-degenerative disorders and
certain cancers. The company’s product candidates have successfully
completed 11 pre-clinical, and 6 Phase I, Phase I/II, and Phase II
clinical studies in various inflammatory diseases indicating its
broad anti-inflammatory effect without evidence of
immunosuppression. In addition to Alzheimer’s disease, NeurMedix
plans to enter clinical trials for the treatment of Parkinson’s
disease and several oncological indications later this year. In
excess of $85 million has been invested in developing NE3107. The
company’s focus is on diseases with significant unmet medical needs
and commercial potential in order to expedite FDA review, minimize
capital requirements and optimize shareholder value.
Contact:Bruce MackleLifeSci Advisors, LLC(929)
469-3859
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