TARRYTOWN, N.Y., Aug. 14, 2019 /PRNewswire/ --
Adding evinacumab reduced LDL cholesterol by 49% in patients
with homozygous familial hypercholesterolemia, compared to
lipid-lowering therapies alone
Evinacumab was generally well-tolerated, and all evinacumab
patients completed the six-month treatment period
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
positive pivotal Phase 3 results for evinacumab, an investigational
angiopoietin-like 3 (ANGPTL3) antibody, in patients with homozygous
familial hypercholesterolemia (HoFH). Patients with HoFH have
severely elevated levels of bad cholesterol (otherwise known as
low-density lipoprotein cholesterol, or LDL cholesterol), and often
experience early atherosclerotic disease, sometimes suffering
cardiac events as early as their teenage years.
On average, patients entered the trial with LDL cholesterol
levels of 255 mg/dL, despite treatment with other lipid-lowering
therapies, including maximally-tolerated statins, PCSK9 (proprotein
convertase subtilisin/kexin type 9) inhibitors, ezetimibe, LDL
apheresis and lomitapide. The trial met its primary endpoint,
showing that adding evinacumab to other lipid-lowering therapies
decreased LDL cholesterol by 49% on average, compared to
lipid-lowering therapies alone.
"Currently HoFH patients face limited choices in reducing their
LDL cholesterol, including therapies that are time-consuming like
LDL apheresis, or that may have side effect concerns. Despite
recent therapeutic advances, there is still a significant unmet
need to lower the LDL cholesterol of many patients with HoFH. On
average, evinacumab reduced patients' LDL cholesterol in half and
was generally well-tolerated in the trial," said George D. Yancopoulos, M.D., Ph.D., President
and Chief Scientific Officer of Regeneron. "These results raise the
potential that evinacumab may have value for other patients with
severe, refractory hypercholesterolemia, where we have a trial
ongoing."
In 2017, the U.S. Food and Drug Administration (FDA) granted
Breakthrough Therapy designation for evinacumab for the
treatment of hypercholesterolemia in patients with HoFH.
Regeneron scientists discovered the angiopoietin gene family
more than two decades ago. Human genetics research published in
The New England Journal of Medicine in 2017 by
scientists from the Regeneron Genetics Center found that patients
whose ANGPTL3 gene did not function properly (called a "loss-of
function mutation") have significantly lower levels of key
blood lipids, including LDL cholesterol, and this is associated
with a significantly lower risk of coronary artery disease.
"People born with homozygous familial hypercholesterolemia – the
rare and most severe form of FH – are in urgent need of additional
therapies to lower life-threatening cholesterol levels. HoFH causes
aggressive heart disease even in childhood, and today's treatments
often are not enough for these individuals," said Katherine Wilemon, Founder and Chief Executive
Officer, FH Foundation. "These evinacumab Phase 3 results bring
hope to those who need it most. The FH Foundation is grateful to
the researchers who advanced this science and the individuals who
participated in this clinical trial."
The Phase 3 trial was designed to assess the effect of
evinacumab on LDL cholesterol and other lipid-related endpoints.
Results from the evinacumab group at week 24 included:
- 49% reduction in LDL cholesterol from baseline, compared to
placebo (47% reduction for evinacumab compared to a 2% increase for
placebo, p<0.0001), the primary endpoint.
- 132 mg/dL absolute change in LDL cholesterol from baseline,
compared to placebo (135 mg/dL reduction for evinacumab compared to
a 3 mg/dL reduction for placebo, p<0.0001).
- 47% achieved LDL cholesterol levels less than 100 mg/dL,
compared to 23% for placebo (nominal p=0.0203).
- Similar levels of LDL cholesterol-lowering were also observed
in the most difficult-to-treat patients who often don't respond to
certain other therapies, described as "null/null" or
"negative/negative" patients.
- Evinacumab also reduced apolipoprotein B (ApoB), non-HDL
cholesterol and total cholesterol compared to placebo.
LDL cholesterol reductions were observed from the first
assessment at week 2, and were maintained throughout the 24-week
double-blind treatment period.
In the trial, evinacumab was generally well-tolerated. During
the double-blind treatment period, 66% of evinacumab patients and
81% of placebo patients experienced an 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). During the double-blind
treatment period there was no difference in the incidence of
nausea, abdominal pain or diarrhea between treatment groups, and
there were no deaths, major adverse cardiovascular events or
hepatic disorders.
HoFH is a serious, rare, genetic condition and affects
approximately 1,300 people in the U.S. Detailed results from this
trial will be presented at a future medical meeting, and data will
be submitted to regulatory authorities, starting with the FDA in
2020.
About Evinacumab
Evinacumab is an investigational,
fully-human, monoclonal antibody that specifically binds to
angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 acts as an inhibitor
of lipoprotein lipase and endothelial lipase, and appears to play a
central role in lipoprotein metabolism. It is currently being
studied in patients with HoFH (Phase 3), refractory
hypercholesterolemia (Phase 2) and severe hypertriglyceridemia
(Phase 2).
About the ELIPSE HoFH Trial
ELIPSE HoFH is an ongoing
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 is reduction of LDL cholesterol with
evinacumab 15 mg/kg compared to placebo after 24 weeks. Secondary
endpoints evaluate safety, tolerability and pharmacokinetics (PK),
as well as the efficacy of evinacumab on LDL cholesterol goal
attainment and other lipid parameters (including ApoB and non-HDL
cholesterol) and whether patients met criteria for needing LDL
apheresis. The trial was not powered to evaluate the effect of
evinacumab on cardiovascular events.
The average age of patients entering the trial was 42 years
(range: 12 to 75). In the evinacumab treatment group, 98% of
patients were on statins, 81% were on PCSK9 inhibitors, 75% were on
ezetimibe, 33% were on LDL apheresis and 26% were on lomitapide. In
addition, 35% of evinacumab patients had the most severe,
"null/null" form of HoFH.
The trial has three treatment periods: 1) up to an eight-week
run-in period; 2) a 24-week double-blind treatment period (DBTP);
3) and an ongoing, 24-week, open-label treatment period (OLTP).
During the OLTP portion of the trial, which is ongoing, all
patients receive evinacumab, regardless of treatment assignment in
the DBTP.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading
biotechnology company that invents life-transforming medicines for
people with serious diseases. Founded and led for 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
disease, allergic and inflammatory diseases, cancer, cardiovascular
and metabolic diseases, infectious diseases, pain and rare
diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune® which produces optimized fully-human
antibodies, and 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.
Forward-Looking Statements and Use of Digital
Media
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involve risks and uncertainties relating to future events and the
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or the "Company"), and actual events or results may differ
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