TARRYTOWN, N.Y., Aug. 19, 2020 /PRNewswire/ --
Patients with homozygous familial hypercholesterolemia (HoFH)
suffer from a severe form of early cardiovascular disease and are
inadequately served by currently available medications
Adding evinacumab to other lipid-lowering therapies cut bad
cholesterol levels in half in patients with HoFH, including for the
most difficult-to-treat patients who had nearly non-existent
LDL-receptor activity
Evinacumab is currently under Priority Review with the FDA;
decision expected by February 11,
2021
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today
announced that the New England Journal of Medicine
(NEJM) published positive results from the Phase 3 trial of
evinacumab in 65 patients with homozygous familial
hypercholesterolemia (HoFH). Evinacumab is an investigational
medicine that binds to and blocks the function of angiopoietin-like
3 (ANGPTL3), and is the first medicine of its kind to show efficacy
in patients with HoFH – including patients with little to no
low-density lipoprotein (LDL) receptor function.
Patients with HoFH have severely elevated levels of bad
cholesterol (low-density lipoprotein cholesterol, or LDL-C), which
increases their risk for premature atherosclerotic disease and
cardiac events as early as their teenage years. Treatment
guidelines recommend early and intensive LDL-C lowering, but
patients with HoFH are less responsive (or unresponsive) to
standard lipid-lowering therapies, including statins and PCSK9
(proprotein convertase subtilisin/kexin type 9) inhibitors.
As initially announced in a topline press release, the trial met
its primary endpoint, showing that patients who added evinacumab to
other lipid-lowering therapies (n=43) reduced their LDL-C from
baseline by 49% compared to lipid-lowering therapies alone
(placebo, n=22) at week 24 (47% reduction evinacumab, 2% increase
placebo, p<0.0001). At the same time point, evinacumab-treated
patients also decreased LDL-C from baseline by 132 mg/dL compared
to placebo (135 mg/dL reduction evinacumab, 3 mg/dL reduction
placebo, p<0.0001). As discussed in the NEJM publication,
genetic loss of ANGPTL3 has been associated with additional
lipid-lowering effects, including lowered triglycerides,
apolipoprotein B (ApoB), HDL and non-HDL cholesterol, and total
cholesterol. Evinacumab treatment mirrored these lipid-lowering
effects.
"The vast majority of my patients with HoFH never reach their
target LDL-C despite taking multiple lipid-lowering therapies, and
they remain at increased risk of premature heart
disease because of their persistently high LDL-C levels," said
Professor Derick J. Raal, MMED,
Ph.D., principal investigator and Professor & Head, Division of
Endocrinology & Metabolism at the University of the
Witwatersrand, South Africa. "If
approved, evinacumab will provide a major step forward for the
treatment of patients with HoFH who have significant unmet
needs."
Researchers also assessed in a post hoc analysis the effect of
evinacumab in patients with nearly non-existent (<2%)
LDL-receptor activity, whose mean baseline LDL-C levels were 258
mg/dL (n=10). Among these patients, evinacumab reduced LDL-C by 72%
from baseline compared to placebo (54% reduction evinacumab, 19%
increase placebo, nominal p=0.005).
During the double-blind treatment period, 66% of evinacumab
patients and 81% of placebo patients experienced at least one
adverse event (AE). AEs that occurred in at least 5% of patients
and more commonly with evinacumab were influenza-like illness (11%
evinacumab, 0% placebo) and rhinorrhea (7% evinacumab, 0% placebo).
There were no deaths, major adverse cardiovascular events or
discontinuations due to AEs.
"Today's publication further demonstrates how evinacumab,
through its novel mechanism of action, was able to reduce LDL-C
levels in patients with all forms of HoFH, even those with nearly
no LDL-receptor activity," said George D.
Yancopoulos, M.D., Ph.D., Co-founder, President and Chief
Scientific Officer at Regeneron. "This validates our genetic-based
approach, where Regeneron ANGPTL3 genetic research directly led to
evinacumab, which we hope can become the standard of care in the
treatment of HoFH."
Previous research published in NEJM in 2017 by the
Regeneron Genetics Center found that people with loss-of-function
mutations in their ANGPTL3 gene have significantly lower levels of
key blood lipids, including LDL-C. By blocking the ANGPTL3 protein,
evinacumab was designed to replicate this loss-of-function mutation
effect to lower LDL-C in people with HoFH.
In the U.S., the Biologics License Application (BLA) for
evinacumab is currently under Priority Review, with a target action
date of February 11, 2021. In 2017,
the U.S. Food and Drug Administration (FDA) granted Breakthrough
Therapy designation to evinacumab for the treatment of
hypercholesterolemia in patients with HoFH. Other regulatory
submissions are ongoing, including in the European Union, where the
European Medicines Agency's Committee for Medicinal Products for
Human Use (CHMP) recommended an accelerated assessment for
evinacumab based on the high unmet medical need and therapeutic
innovation demonstrated by the product. The safety and efficacy of
evinacumab have not been fully evaluated by any regulatory
authority.
About evinacumab and the ELIPSE HoFH Trial
Evinacumab is an investigational fully-human monoclonal antibody
that binds to and blocks the function of ANGPTL3 and is currently
being studied in patients with HoFH (ongoing Phase 3 extension
trial), refractory hypercholesterolemia (Phase 2) and severe
hypertriglyceridemia (Phase 2).
Regeneron invented evinacumab using the company's
VelocImmune® technology, a proprietary
genetically-engineered mouse platform endowed with a
genetically-humanized immune system to produce optimized
fully-human monoclonal antibodies. VelocImmune
technology has been used to create multiple FDA-approved
antibodies including Praluent® (alirocumab),
Dupixent® (dupilumab), Libtayo®
(cemiplimab-rwlc) and Kevzara® (sarilumab). Regeneron
previously used these technologies to rapidly develop a treatment
for Ebola virus infection, which is currently under review by the
FDA, and is now being used in efforts to create prophylactic and
treatment medicines for COVID-19.
ELIPSE (Evinacumab LIPid StudiEs) HoFH was a multi-national
Phase 3 randomized, double-blind, placebo-controlled,
parallel-group trial evaluating the efficacy and safety of
evinacumab 15 mg/kg administered intravenously every four weeks in
65 patients aged 12 years or older with HoFH (43 evinacumab, 22
placebo). The primary endpoint was reduction of LDL-C from baseline
with evinacumab compared to placebo at 24 weeks.
About Regeneron
Regeneron (NASDAQ:
REGN) is a leading biotechnology company that invents
life-transforming medicines for people with serious diseases.
Founded and led for over 30 years by physician-scientists, our
unique ability to repeatedly and consistently translate science
into medicine has led to seven FDA-approved treatments and numerous
product candidates in development, all of which were homegrown in
our laboratories. Our medicines and pipeline are designed to help
patients with eye diseases, allergic and inflammatory diseases,
cancer, cardiovascular and metabolic diseases, pain, infectious
diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our
proprietary VelociSuite® technologies,
such as VelocImmune, which uses unique
genetically-humanized mice to produce optimized fully-human
antibodies and bispecific antibodies, and through ambitious
research initiatives such as the Regeneron Genetics Center, which
is conducting one of the largest genetics sequencing efforts in the
world.
For additional information about the company, please
visit www.regeneron.com or follow @Regeneron on
Twitter.
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