TARRYTOWN, N.Y., March 30, 2020 /PRNewswire/ --
Results from separate positive Phase 3 trial of
Praluent® (alirocumab) in patients with HoFH also
presented; FDA regulatory submission planned for Q2 2020
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)
announced that detailed Phase 3 results of evinacumab were
presented today as a late-breaking presentation at the American
College of Cardiology's Annual Scientific Session together with
World Congress of Cardiology (ACC.20). Evinacumab is an
investigational fully-human monoclonal antibody that binds to and
blocks the function of angiopoietin-like 3 (ANGPTL3), in patients
with homozygous familial hypercholesterolemia (HoFH). Regeneron
previously announced topline positive results of this trial in
August 2019.
HoFH is an inherited disease in which patients have severely
elevated levels of bad cholesterol (otherwise known as low-density
lipoprotein cholesterol, or LDL-C) and often experience early
atherosclerotic disease, sometimes suffering cardiac events in
their teenage years. Most patients with HoFH are less responsive
(or unresponsive) to standard lipid-lowering therapies, including
statins and PCSK9 inhibitors, which act mainly by inducing LDL
receptor function, leaving these patients with high unmet need.
Evinacumab acts by a different mechanism than other lipid-lowering
therapies, raising the possibility that it might offer patients
with HoFH profound LDL-C reductions. Supporting this possibility,
genetic research has shown that reduction of ANGPTL3 is associated
with decreased LDL-C levels, as well as significantly lower risk of
coronary artery disease.
In this Phase 3 trial, patients who added evinacumab to other
lipid-lowering therapies reduced their LDL-C by 49% from baseline
at 24 weeks compared to the placebo group, who received other
lipid-lowering therapies alone, the primary endpoint of the trial
(p<0.0001). Nearly all (95%) patients in the evinacumab arm
entered the trial on statins and 79% were on PCSK9 (proprotein
convertase subtilisin/kexin type 9) inhibitors. Nearly half of
evinacumab-treated patients reduced LDL-C to under 100 mg/dL
(nominal p=0.0203), despite entering the trial with average LDL-C
levels of 260 mg/dL on other lipid-lowering
therapies.
"As a doctor, it can be heart-wrenching to see HoFH patients
struggle to lower their potentially life-threatening LDL-C levels,
despite taking every medical treatment available to them," 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. "In
this trial, for the first time, evinacumab-treated HoFH patients
lowered their LDL-C to previously unattainable levels, with nearly
half achieving an LDL-C range that is considered 'normal' for
healthy adults."
"Despite medical advances, cardiovascular disease tragically
remains the number one cause of death for men and women worldwide.
Regeneron remains committed to advance medicines for people who
have significant unmet need, including those with HoFH, and we are
grateful to the patients and doctors who participated in our
trials," said George D. Yancopoulos,
M.D., Ph.D., Co-founder, President and Chief Scientific Officer of
Regeneron. "Our investments in genetic research and biology enable
us to identify completely new ways of targeting diseases.
Evinacumab, a first-of-its-kind antibody that works entirely
differently to other HoFH medicines, exemplifies the potential of
genetic-based research to revolutionize patient treatment."
Also shared today were Phase 3 results from another
late-breaking presentation, demonstrating the effect of
Praluent® (alirocumab) on patients with HoFH. The trial
met its primary endpoint, with Praluent-treated patients reducing
their LDL-C by over a third at week 12, compared to placebo
(p<0.0001). In addition, more than a quarter of patients reduced
their LDL-C by at least half (p=0.0017), despite entering the trial
with average LDL-C levels of 295 mg/dL while being on other
lipid-lowering therapies and/or apheresis. No new safety signals
were identified in the trial. The use of Praluent in patients with
HoFH is investigational and the safety and efficacy have not been
evaluated by any regulatory authority.
Detailed ELIPSE HoFH Results
In the Phase 3
ELIPSE HoFH trial, 65 patients were randomized to receive either
evinacumab 15 mg/kg intravenously every four weeks (n=43) plus
other lipid-lowering therapies, versus lipid-lowering therapies
alone (placebo, n=22). At baseline, LDL-C was 260 mg/dL in the
evinacumab group and 247 mg/dL in the placebo
group.
The ELIPSE HoFH trial met its primary endpoint, with
evinacumab-treated patients reducing their LDL-C from baseline by
49% compared to placebo at week 24 (47% reduction evinacumab, 2%
increase placebo, p<0.0001). At the same time point, compared to
baseline evinacumab-treated patients also experienced:
- Average LDL-C decreased by 132 mg/dL compared to placebo (135
mg/dL reduction evinacumab, 3 mg/dL reduction placebo,
p<0.0001).
- 47% achieved LDL-C less than 100 mg/dL, compared to 23% in the
placebo arm (nominal p=0.0203).
- More than three-fourths (84%) reduced their LDL-C by at least
30% and more than half (56%) reduced their LDL-C by at least 50%,
compared to 19% and 5% for placebo, respectively (p<0.0001 and
p=0.0003).
- Significant reductions were also observed in other key
secondary endpoints including levels of apolipoprotein B (ApoB),
non-high-density lipoprotein cholesterol (non-HDL-C), total
cholesterol and triglycerides, compared to placebo (p<0.0001 for
all).
- Similar levels of LDL-C 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.
In the trial, evinacumab was generally well-tolerated. During
the double-blind treatment period, 66% of evinacumab patients and
81% of placebo patients experienced at least one adverse event
(AE). During the double-blind treatment period, 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.
Detailed results from this trial will be used as the basis of
regulatory submissions around the world, with the U.S. Food and
Drug Administration (FDA) submission expected to be completed by
mid-2020.
Detailed ODYSSEY HoFH Results
In the Phase 3
ODYSSEY HoFH trial, 69 patients were randomized to receive either
Praluent (n=45) plus other lipid-lowering therapies, excluding
other PCSK9 inhibitors, versus lipid-lowering therapies alone
(placebo, n=24). At baseline, LDL-C was 295 mg/dL in the Praluent
group and 260 mg/dL in the placebo group; nearly all (>95%)
patients were on a statin.
The trial met its primary endpoint, with Praluent-treated
patients experiencing a 36% reduction in LDL-C at week 12 compared
to placebo (27% reduction Praluent, 9% increase placebo,
p<0.0001). At the same time point, compared to baseline
Praluent-treated patients also experienced:
- Average LDL-C levels decreased by 72 mg/dL compared to placebo
(63 mg/dL reduction Praluent, 9 mg/dL increase placebo).
- More than half (57%) reduced their LDL-C by at least 30% and
more than a quarter (27%) reduced their LDL-C by at least half,
compared to 4% and 0% for placebo, respectively (p=0.0010 and
p=0.0017).
No serious AEs, permanent treatment discontinuations or deaths
were reported during the double-blind treatment period. During the
double-blind treatment period, the AE that occurred in at least 5%
of patients, and more commonly with Praluent, was diarrhea (7%
Praluent, 0% placebo). AEs that occurred in at least 5% of
patients, and more commonly with placebo, were upper respiratory
tract infection (4% Praluent, 8% placebo) and headache (4%
Praluent, 8% placebo).
Research into the use of Praluent in patients with HoFH is
investigational and the safety and efficacy for this use have not
been evaluated by any regulatory authority. Regeneron plans to
submit these data as the basis of regulatory submissions with the
FDA in the second quarter of 2020.
About evinacumab and the ELIPSE HoFH Trial
Evinacumab
is a fully-human antibody that blocks ANGPTL3 and was invented by
Regeneron using the company's proprietary
VelocImmune® technology that utilizes 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.
Evinacumab is currently being studied in patients with HoFH
(Phase 3), refractory hypercholesterolemia (Phase 2) and severe
hypertriglyceridemia (Phase 2). In 2017, the 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-C, and this is associated with a
significantly lower risk of coronary artery disease.
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 was reduction of
LDL-C from baseline with evinacumab compared to placebo at 24
weeks.
About Praluent and the ODYSSSEY HoFH Trial
Praluent® (alirocumab) inhibits the binding of PCSK9
(proprotein convertase subtilisin/kexin type 9) to the LDL receptor
and thereby increases the number of available LDL receptors on the
surface of liver cells to clear LDL, which lowers LDL-C levels in
the blood. Praluent was developed by Regeneron and Sanofi under a
global collaboration agreement and invented by Regeneron using the
company's proprietary VelocImmune® technology. In
December 2019, the companies
announced their intent to simplify the Praluent collaboration, with
Regeneron expected to gain sole U.S. rights and Sanofi expected to
gain sole ex-U.S. rights.
Praluent is approved in more than 60 countries worldwide,
including the U.S., Japan,
Canada, Switzerland, Mexico, Brazil and the EU. In the U.S., Praluent is
approved to reduce the risk of heart attack, stroke and unstable
angina requiring hospitalization in adults with established
cardiovascular disease. Praluent is also approved as an adjunct to
diet, alone or in combination with other lipid lowering therapies
(e.g., statins, ezetimibe), for the treatment of adults with
primary hyperlipidemia (including heterozygous familial
hypercholesterolemia) to reduce LDL-C.
Research into the use of Praluent in patients with HoFH remains
investigational, and the safety and efficacy for this use have not
been evaluated by any regulatory authority.
In the Phase 3 ODYSSEY HoFH trial, patients on
maximally-tolerated stains and/or apheresis were randomized to
receive either Praluent 150 mg subcutaneously every 2 weeks (n=45)
or placebo (n=24). The primary endpoint was reduction of LDL-C from
baseline with Praluent compared to placebo at 12 weeks.
Important Praluent Safety Information for the U.S.
Do
not use Praluent if you are allergic to alirocumab or to any of the
ingredients in Praluent.
Before you start using Praluent, tell your healthcare provider
about all of your medical conditions, including allergies, and if
you are pregnant or plan to become pregnant or if you are
breastfeeding or plan to breastfeed.
Tell your healthcare provider or pharmacist about any medicines
you take, including prescription and over-the-counter medicines,
vitamins or herbal supplements.
Praluent can cause serious side effects, including allergic
reactions that can be severe and require treatment in a hospital.
Stop using Praluent and call your healthcare provider or go to the
nearest hospital emergency room right away if you have any symptoms
of an allergic reaction including a severe rash, redness, hives,
severe itching, trouble breathing or swelling of the face, lips,
throat, or tongue.
The most common side effects of Praluent include: redness,
itching, swelling, or pain/tenderness at the injection site,
symptoms of the common cold, and flu or flu-like symptoms. Tell
your healthcare provider if you have any side effect that bothers
you or that does not go away.
Talk to your doctor about the right way to prepare and give
yourself a Praluent injection and follow the "Instructions For Use"
that comes with Praluent.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
Praluent is an injectable prescription medicine used:
- in adults with cardiovascular disease to reduce the risk of
heart attack, stroke, and certain types of chest pain conditions
(unstable angina) requiring hospitalization.
- along with diet, alone or together with other
cholesterol-lowering medicines in adults with high blood
cholesterol levels called primary hyperlipidemia (including a type
of high cholesterol called heterozygous familial
hypercholesterolemia), to reduce low-density lipoprotein
cholesterol (LDL-C) or bad cholesterol.
It is not known if Praluent is safe and effective in
children.
Please click here for the full Prescribing
Information.
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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