Cerenis Therapeutics Announces Last Patient Dosed in CARAT Phase II Study

Cerenis Therapeutics (Euronext: CEREN- ISIN: FR0012616852), an international biopharmaceutical company dedicated to the discovery and development of innovative HDL (good cholesterol) therapies for treating
cardiovascular and metabolic diseases, announces the dosing of the last patient in the global Phase II CARAT study. CARAT is designed to assess the therapeutic efficacy of CER-001, a pre-beta HDL mimetic, in post-acute coronary syndrome (ACS) patients.
Enrollment in CARAT was completed in August 2016 and the last patient
has now received the final infusion of CER-001 or placebo. The last
patients will undergo intravascular ultrasound (IVUS) imaging of the
coronary arteries in the coming weeks and the final follow-up safety
visit is expected to occur at the end of the month. Data analysis will
commence thereafter and the Company expects to report topline results no
later than the first quarter of 2017.
Dr. Jean-Louis Dasseux, founder and CEO of Cerenis, commented: “We are
delighted to have completed patient dosing and to be nearing the end of
the clinical portion of CARAT. Of note, we have reached this stage of
the study ahead of schedule. Data collection and analysis will involve
imaging of 301 patients who were randomized to either CER-001 or placebo
over nine weeks, followed by 30 days of observation, including a
follow-up IVUS conducted two weeks after dosing. The design of the CARAT
trial and the selection of the optimal dose were based on multiple
successful previous studies, and we look forward to announcing topline
results no later than the first quarter of 2017”.
Despite secondary prevention measures, the persistent risk of recurrence
of a heart attack for patients who have experienced an ACS event remains
very high and represents a significant and unmet medical need. By
enabling the rapid regression of atherosclerotic plaque, CER-001 could
potentially provide an opportunity to reduce the risk of recurrent
cardiovascular events during the first few months following an ACS
event. Hence CER-001, in addition to long-term LDL-C lowering
treatments, could produce further reductions in morbidity and mortality
and become the new standard of care for treating patients following an
ACS.
About the CARAT Study
CARAT is a double-blind, placebo-controlled Phase II study designed to
assess the impact of CER-001 on the regression of atherosclerotic plaque
in post-ACS patients by measuring the percent atheroma volume (PAV)
using IVUS imaging of the coronary arteries. The primary endpoint is the
percentage change from baseline in PAV compared with placebo in a study
population with an estimated baseline PAV ≥30% in the target coronary
artery.
A total of 301 patients were randomized to either 3 mg/kg of CER-001 or
placebo in a 1:1 ratio on Day 1 and weekly thereafter for a total of 10
infusions, followed by a 30-day observation period, including a
follow-up IVUS two weeks post-dose. The study was conducted at 35 sites
in Australia, Hungary, the Netherlands and the United States under the
supervision of a prestigious steering committee. Prof. Stephen Nicholls
of the Heart Health Research team at SAHMRI (South Australian Health and
Medical Research Institute, Adelaide, Australia) is the principal
investigator.
The CARAT study draws on findings from prior clinical trials,
particularly the positive data presented in November 2015 at the
American Heart Association Scientific Congress by the Prof. Stephen
Nicholls, to establish whether CER-001 promotes plaque regression in
patients following an ACS. The 3 mg/kg dose was selected as optimal
taking into account clinical and preclinical findings that confirm a
larger number of CER-001 administrations at a low dose are more
effective at plaque regression than a smaller number of high-dose
administrations.¹
Periodic safety reviews were performed during the treatment period by a
data safety monitoring board (DSMB), which included surveillance of
laboratory testing and on-treatment safety events. To date no safety or
tolerability issues have been identified in patients enrolled in the
CARAT trial.
About CER-001
CER-001 is an engineered complex of recombinant human apolipoprotein A-1
(apoA-I), the major structural protein of HDL, and phospholipids. It is
designed to mimic the structure and function of natural, nascent HDL,
also known as pre-beta HDL. Its mechanism of action is to increase
apoA-I and the number of HDL particles transiently, to stimulate the
removal of excess cholesterol and other lipids from tissues including
the arterial wall and to transport them to the liver for elimination
through a process called Reverse Lipid Transport. Previous Phase II
studies have provided important data demonstrating the efficacy of
CER-001 in regressing atherosclerosis in several distinct vascular beds
in patients representing the entire spectrum of cholesterol homeostasis.
The totality of the data to date indicates that CER-001 performs all of
the functions of natural pre-beta HDL particles and has the potential to
be the best-in-class HDL mimetic.
About Post-Acute Coronary Syndrome
Approximately 12% of ACS patients experience a recurrent cardiovascular
event within one year of the initial event.² The risk of
recurrence is especially high during the first two months, during which
time over half of the deaths and major cardiac events occur.
The target post-ACS population for CER-001 is estimated to be
approximately 2.8 million patients per year for North America and Europe.
About Cerenis Therapeutics
Cerenis Therapeutics is an international biopharmaceutical company
dedicated to the discovery and development of innovative HDL therapies
for the treatment of cardiovascular and metabolic diseases. HDL is the
primary mediator of the reverse lipid transport, or RLT, the only
natural pathway by which excess cholesterol is removed from arteries and
is transported to the liver for elimination from the body. Cerenis is
developing a portfolio of HDL therapies, including HDL mimetics for the
rapid regression of atherosclerotic plaque in high-risk patients such as
post-ACS patients and patients with HDL deficiency, and drugs that
increase HDL for patients with a low number of HDL particles to treat
atherosclerosis and associated metabolic diseases. Cerenis is well
positioned to become a leader in HDL therapeutics, with a broad
portfolio of programs being developed. Since its inception in 2005, the
company has been funded by top-tier investors including Sofinnova
Partners, HealthCap, Alta Partners, EDF Ventures, Daiwa Corporate
Investment, TVM Capital, Orbimed, IRDI/IXO Private Equity and Bpifrance.
In March 2015 Cerenis completed an IPO on Euronext raising €53.4m.
Please visit www.cerenis.com.
¹ Kataoka Y, et al. Greater regression of coronary
atherosclerosis with the pre-beta high-density lipoprotein mimetic
CER-001 in patients with more extensive plaque burden. Circulation 2015;
132: A12156.
² Cornel, J. et al., for the PLATO study group. Prior smoking
status, clinical outcomes, and the comparison of ticagrelor with
clopidogrel in acute coronary syndromes-insights from the PLATelet
inhibition and patient Outcomes (PLATO) trial. Am Heart J 2012, 164, 3,
334–342.e1.