Evidence supports P. gingivalis as a driver of
Alzheimer’s in easily identified patient population
Successful identification of target population
and therapeutic dose inform next steps
Cortexyme, Inc. (Nasdaq: CRTX) will present additional data from
its Phase 2/3 GAIN Trial at the 14th Clinical Trials on Alzheimer's
Disease Conference (CTAD 2021) as a part of the meeting’s
Late-Breaking Readout Roundtable program today, Thursday, November
11, 2021, at 11:35 a.m. Eastern Time taking place in Boston,
Massachusetts, as well as virtually. The presentation will expand
on previously reported top-line results that demonstrated the
relationship between the reduction of Porphyromonas gingivalis (P.
gingivalis) infection and the slowing of cognitive decline in
Alzheimer’s disease with atuzaginstat treatment in a prespecified
population of patients based on diagnosis of infection.
The 643-participant 48-week GAIN Trial was the first large study
to test the efficacy of an oral small-molecule targeting P.
gingivalis for disease modification in mild to moderate Alzheimer’s
patients. While not meeting statistical significance on its
co-primary cognitive and functional endpoints in the overall
cohort, the study data showed that treatment with atuzaginstat
slowed decline compared to placebo on the majority of clinical
endpoints in prespecified populations that were selected based on
P. gingivalis infection markers.
The GAIN Trial results showed that the 40 mg BID arm
demonstrated equivalent or better efficacy across key endpoints
compared to the higher dose, 80 mg BID, as well as a superior
safety profile. Trends to benefit at 40 mg BID were seen with
multiple prespecified analytic approaches, including on ADAS-Cog11,
CDR-SB, MMSE, and NPI, with increasing separation from placebo
throughout the study consistent with disease modification. Benefits
were not seen on ADCS-ADL at either dose. Changes in P. gingivalis
DNA levels in saliva correlated significantly with clinical
outcomes during and at the end of treatment, demonstrating that
reduced P. gingivalis bacterial load resulted in better clinical
outcomes. A trend to slowing of the primary biomarker endpoint of
hippocampal atrophy was seen in treatment groups, but did not reach
significance.
“Our ability to identify the right population in historically
hard to treat mild to moderate Alzheimer’s patients, along with
finding an efficacious dose with a differentiated safety profile,
is important progress toward a breakthrough treatment for
Alzheimer’s disease,” said Michael Detke, MD, PhD, Cortexyme’s
chief medical officer. “We saw clinically significant effects
ranging from 30% to 50% slowing on ADAS-Cog11 and CDR-SB measures.
The benefits on these widely accepted scales provide an informative
foundation for a confirmatory study. This landmark study materially
advances our understanding of P. gingivalis as an upstream driver
of Alzheimer’s disease progression, and we look forward to sharing
additional study data as it becomes available over the coming
months.”
“The GAIN Trial achieved several significant advancements for
the Alzheimer’s field, first by clinically confirming that P.
gingivalis is a key upstream driver of disease progression.
Further, the data demonstrated a compelling risk-benefit profile
with a clinically significant treatment response in an easily
identifiable population of patients,” said Marwan Sabbagh, MD,
FAAN, lead investigator of the GAIN Trial and Professor of
Neurology at the Barrow Neurological Institute. “I am particularly
encouraged by GAIN’s identification of a target population, which
is consistent with the heterogeneous nature of Alzheimer’s disease
and comparable to treatment advancements based on diagnosis of
infectious disease, like HIV dementia and personalized medicine
common in other therapeutic areas, like oncology. When coupled with
the convenience of oral dosing, atuzaginstat offers the potential
to fill a huge gap in the underserved mild to moderate Alzheimer’s
population in as many as half of those patients. I was gratified to
act as the lead investigator for this important study that will
hopefully be part of our arsenal of treatments for Alzheimer’s in
the not-so-distant future.”
Across critical safety measures, the rates in the 40 mg BID
treatment arm were either comparable to placebo or substantially
better than in the 80 mg BID arm. Most adverse events were mild to
moderate in severity. The most common were gastrointestinal, such
as diarrhea in up to 16% and nausea in 6% of participants treated
with atuzaginstat, versus 3% and 2% of placebo participants,
respectively. Atuzaginstat was associated with dose-related liver
enzyme elevations >3X the upper limit of normal: 2% on placebo,
7% on 40 mg BID, and 15% on 80 mg BID. These elevations alone were
not clinically significant and virtually all participants were
asymptomatic. Two participants in the 80 mg BID arm had concomitant
bilirubin elevations without alternative explanation. Lab changes
resolved while participants remained on drug or after withdrawal
without any known long-term adverse effects. Atuzaginstat treated
groups showed no increase in ARIA (amyloid-related imaging
abnormalities), including microhemorrhage and edema, or superficial
siderosis.
“The data generated from this first-of-its-kind study adds an
important new dimension to our understanding of Alzheimer’s
disease,” said Casey Lynch, Cortexyme’s chief executive officer,
co-founder, and chair. “The study was successful in accomplishing
many of our objectives, including identification of the appropriate
population for treatment and the therapeutic dose. We intend to
apply our learnings to progress an anticipated confirmatory study,
pending discussions with the FDA and global regulators.”
Accessing Cortexyme’s Late-Breaking Readout Roundtable at
CTAD 2021
Cortexyme’s late-breaking readout roundtable presentation at
CTAD 2021 will be accessible today, Thursday, November 11, 2021,
beginning at 11:35 a.m. Eastern Time via the company’s Investor
Relations website at ir.cortexyme.com, in addition to being
accessible to CTAD registered meeting attendees in-person and on
its virtual platform.
About Cortexyme
Cortexyme, Inc. (Nasdaq: CRTX) is a clinical stage
biopharmaceutical company pioneering upstream therapeutic
approaches designed to improve the lives of patients diagnosed with
Alzheimer’s and other degenerative diseases. Cortexyme’s lead
program targets a specific, infectious pathogen called P.
gingivalis found in the brain of Alzheimer’s patients and other
organs and tied to degeneration and inflammation in humans and
animal models. The company’s causation evidence for Alzheimer’s
disease and the mechanism of its novel therapeutic has been
independently replicated and confirmed by multiple laboratories
around the world, as well as published in peer-reviewed scientific
journals. To learn more about Cortexyme, visit www.cortexyme.com or
follow @Cortexyme on Twitter.
Forward-Looking Statements
Statements in this news release contain “forward-looking
statements” that are subject to substantial risks and
uncertainties. Forward-looking statements contained in this news
release may be identified by the use of words such as “anticipate,”
“expect,” “believe,” “will,” “may,” “should,” “estimate,”
“project,” “outlook,” “forecast,” “potential” or other similar
words. Examples of forward-looking statements include, among
others, the strategic development path for atuzaginstat, its
business plans, strategy, planned clinical trials and timeline,
prospects, and milestone expectations; the timing and success of
the company’s clinical trials and related data, including plans and
the ability to conduct a confirmatory study with respect to the
GAIN Trial; the potential of atuzaginstat to treat Alzheimer’s
disease; the timing of announcements and updates relating to its
clinical trials and related data; the potential therapeutic
benefits, safety and efficacy of the company’s product candidate or
library of compounds and statements about its ability to obtain,
and the timing relating to, further development of atuzaginstat,
regulatory submissions and interactions with regulators, and
related response and decisions, including with respect to the
company’s partial clinical hold, and approvals with respect to the
company’s drug product candidate. Forward-looking statements are
based on Cortexyme’s current expectations and are subject to
inherent uncertainties, risks, and assumptions that are difficult
to predict and could cause actual results to differ materially from
what the company expects. Further, certain forward-looking
statements are based on assumptions as to future events that may
not prove to be accurate. Factors that could cause actual results
to differ include, but are not limited to, the risks and
uncertainties described in the section titled “Risk Factors” in
Cortexyme’s Annual Report on Form 10-K filed with the Securities
and Exchange Commission (SEC) on March 1, 2021, its Quarterly
Report on Form 10-Q filed with the SEC on October 29, 2021, and
other reports as filed with the SEC. Forward-looking statements
contained in this news release are made as of this date, and
Cortexyme undertakes no duty to update such information except as
required under applicable law.
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version on businesswire.com: https://www.businesswire.com/news/home/20211111005705/en/
Stacy Roughan Cortexyme, Inc. Vice President, Corporate
Communications & Investor Relations ir@cortexyme.com
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