TARRYTOWN, N.Y., March 30, 2021 /PRNewswire/ --
Protocol W trial data confirm results from PANORAMA trial
showing EYLEA significantly reduced vision-threatening
complications and improved anatomic measures of diabetic
retinopathy
Although patients' overall vision was similar in the EYLEA
and sham groups at two years in Protocol W, a new analysis from
PANORAMA shows that delaying EYLEA treatment (sham group) was
associated with prolonged periods of vision loss
Two diabetic retinopathy trials (Protocol W and PANORAMA)
have now shown the benefit of EYLEA every 16 weeks following an
initial dosing period; Regeneron to discuss 16-week dosing interval
with U.S. FDA
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
JAMA Ophthalmology has published initial results from the
National Institutes of Health-sponsored Protocol W trial assessing
EYLEA® (aflibercept) Injection in patients with moderate
to severe non-proliferative diabetic retinopathy (NPDR), without
center-involved diabetic macular edema (CI-DME). At two years, the
primary outcome of the trial showed a 68% reduced risk of
developing vision-threatening complications (either proliferative
diabetic retinopathy [PDR] or CI-DME with vision loss) in patients
who received the EYLEA every-16-weeks dosing regimen. In
comparison, patients receiving sham injections were almost five
times more likely to experience disease progression requiring EYLEA
rescue therapy.
Although at the two-year time point of Protocol W, preventive
EYLEA treatment did not confer a significant difference in visual
acuity versus delayed EYLEA treatment following vision-threatening
complications (i.e., sham), a recent Regeneron follow-up analysis
in the similarly designed PANORAMA trial found that delaying EYLEA
treatment resulted in three times as many patients suffering
prolonged vision loss, compared to those receiving preventive EYLEA
treatment, during a two-year period. A similar analysis has not yet
been conducted for Protocol W.
"Blindness is one of the most feared consequences of diabetic
retinopathy, and we thank the National Eye Institute and the DRCR
Retina Network for conducting a well-controlled trial that provides
useful information to guide treatment in these patients," said
George D. Yancopoulos, M.D., Ph.D.,
President and Chief Scientific
Officer at Regeneron. "Protocol W confirms the landmark results of
the similarly-designed PANORAMA trial, underscoring the importance
of early and regular diabetic retinopathy treatment and the ability
of EYLEA to substantially reduce vision-threatening complications
and improve disease severity. Importantly, these results were
obtained with an every-16-weeks EYLEA dosing regimen, confirming
the efficacy with EYLEA seen in the PANORAMA trial."
In Protocol W, patients were randomly assigned to receive either
EYLEA (2 mg, n=200 eyes) every 16 weeks, after receiving four
initial doses at weeks 0, 4, 8 and 16, or sham (n=199 eyes).
Patients had excellent vision when they entered the trial, with
more than three-quarters of eyes having 20/20 visual acuity or
better (78% EYLEA, 81% sham). Rescue therapy (primarily EYLEA) was
administered to patients if they developed either PDR or
CI-DME.
Compared to sham, EYLEA-treated patients were:
- 68% less likely to develop CI-DME with vision loss or
PDR, the primary outcome measure at two years
(p<0.001).
-
- The cumulative probability of developing PDR or CI-DME with
vision loss was 16% with EYLEA versus 44% with sham. EYLEA patients
were 66% less likely to develop PDR (p<0.001) and 64% less
likely to develop CI-DME with vision loss (p=0.002).
- Three times more likely to experience at least a two-step
improvement in their DR severity score (DRSS). In total, 69
(45%) EYLEA patients experienced at least a two-step improvement,
versus 22 (14%) of those in the sham group (adjusted odds ratio
[OR]: 5.91; p<0.001).
- Five times less likely to require rescue therapy with
EYLEA due to PDR or DME (4% EYLEA, 19% sham). Other rescue
treatments were panretinal photocoagulation (PRP) (<1% EYLEA, 2%
sham), vitrectomy for PDR (<1% EYLEA, <1% sham) and
focal/grid laser treatment for DME (0% EYLEA, 2% sham).
In the retrospective PANORAMA analysis of vision outcomes over
two years, three times more patients in the sham group suffered
from prolonged vision loss (range: 6 weeks to 6 months), compared
to the EYLEA every-16-weeks dosing group (12 of 135 EYLEA, 38 of
133 sham). Results by loss of letters were as follows (as measured
by the Early Treatment Diabetic Retinopathy Study [ETDRS]
chart):
- ≥5 letter loss: 9% EYLEA versus 29% sham, nominal
p<0.0001.
- ≥10 letter loss: 5% EYLEA versus 14% sham,
nominal p=0.0212.
- ≥15 letter loss: 3% EYLEA versus 8% sham,
nominal p=0.0672.
No new safety signals were identified in Protocol W, consistent
with the known safety profile of EYLEA. Ocular adverse events (AEs)
included endophthalmitis (n=3 EYLEA, n=0 sham). The rate of any
cardiovascular/cerebrovascular AEs was not significantly different
among the treatment groups (9% of patients treated with EYLEA in
one eye, 9% of patients treated with sham in one eye, and 8% of
patients treated with both EYLEA [one eye] and sham [other
eye]).
"Diabetic retinopathy is the leading cause of blindness among
working adults. However, vision loss is often preventable if
proactive measures are taken by patients and their doctors," said
Allen C. Ho, M.D., Attending Surgeon
and Director of Retina Research at Wills Eye Hospital in
Philadelphia, PA. "Past trials
have shown that early systemic and ocular intervention in diabetic
eye disease can lead to sustained improvements in visual acuity
over the long term, while undertreatment can put patients' vision
at risk. The latest data from Protocol W and PANORAMA support this
treatment philosophy by showing that an every-16-week EYLEA regimen
helped patients avoid vision-threatening complications and
prolonged periods of vision loss over two years. I look forward to
seeing additional Protocol W vision outcomes at four years."
EYLEA is the only vascular endothelial growth factor (VEGF)
inhibitor that is U.S. Food and Drug Administration (FDA) approved
with two dosing intervals for DR, allowing doctors to customize
treatment. In DR, EYLEA may be dosed every eight weeks following
five initial monthly injections, or every four weeks. EYLEA is not
approved for 16-week dosing as was studied in Protocol W.
About Protocol W
Protocol W is a four-year,
randomized, multi-center, controlled Phase 3 trial (n=399 eyes)
designed to determine the efficacy of EYLEA compared to sham in
preventing vision-threatening complications in high risk patients.
The primary outcome at two years was time to development of CI-DME
with vision loss or PDR. Key secondary outcomes included
development of any PDR or DME criteria based on reading center
assessment, as well as development of CI-DME with a ≥10% and ≥25
micron increase in center subfield thickness. Per the trial
protocol, Protocol W will continue for another two years, when the
second primary outcome will assess visual acuity outcomes between
the two groups at four years.
The Clinicaltrials.gov identifier for this trial is
NCT02634333. The trial was supported by the National Eye
Institute (NEI) and the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), with funding through the
Special Diabetes Program, through a cooperative agreement
(EY14231).
About Diabetic Retinopathy
Approximately eight
million people live with diabetic retinopathy, a disease
characterized by microvascular damage to the blood vessels in the
retina often caused by poor blood sugar control in people with
diabetes. The disease generally starts as NPDR and often has no
warning signs or symptoms. NPDR may progress to PDR, a stage of the
disease in which abnormal blood vessels grow onto the surface of
the retina and into the vitreous cavity, potentially causing severe
vision loss. DME can occur at any stage of DR as the blood vessels
in the retina become increasingly fragile and leak fluid,
potentially causing visual impairment. In the U.S., approximately
1.5 million adults are diagnosed with DME, while approximately 3.5
million people have DR without DME.
About EYLEA® (aflibercept)
Injection
EYLEA® (aflibercept) Injection is
a VEGF inhibitor formulated as an injection for the eye. It is
designed to block the growth of new blood vessels and decrease the
ability of fluid to pass through blood vessels (vascular
permeability) in the eye by blocking VEGF-A and placental growth
factor (PLGF), two growth factors involved in angiogenesis. In the
U.S., EYLEA is the market-leading, FDA-approved anti-VEGF treatment
for its approved indications and is supported by a robust body of
research that includes eight pivotal Phase 3 trials.
IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION
- EYLEA®(aflibercept) Injection is contraindicated in
patients with ocular or periocular infections, active intraocular
inflammation, or known hypersensitivity to aflibercept or to any of
the excipients in EYLEA.
- Intravitreal injections, including those with EYLEA, have been
associated with endophthalmitis and retinal detachments. Proper
aseptic injection technique must always be used when administering
EYLEA. Patients should be instructed to report any symptoms
suggestive of endophthalmitis or retinal detachment without delay
and should be managed appropriately. Intraocular inflammation has
been reported with the use of EYLEA.
- Acute increases in intraocular pressure have been seen within
60 minutes of intravitreal injection, including with EYLEA.
Sustained increases in intraocular pressure have also been reported
after repeated intravitreal dosing with VEGF inhibitors.
Intraocular pressure and the perfusion of the optic nerve head
should be monitored and managed appropriately.
- There is a potential risk of arterial thromboembolic events
(ATEs) following intravitreal use of VEGF inhibitors, including
EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial
infarction, or vascular death (including deaths of unknown cause).
The incidence of reported thromboembolic events in wet AMD studies
during the first year was 1.8% (32 out of 1824) in the combined
group of patients treated with EYLEA compared with 1.5% (9 out of
595) in patients treated with ranibizumab; through 96 weeks, the
incidence was 3.3% (60 out of 1824) in the EYLEA group compared
with 3.2% (19 out of 595) in the ranibizumab group. The incidence
in the DME studies from baseline to week 52 was 3.3% (19 out of
578) in the combined group of patients treated with EYLEA compared
with 2.8% (8 out of 287) in the control group; from baseline to
week 100, the incidence was 6.4% (37 out of 578) in the combined
group of patients treated with EYLEA compared with 4.2% (12 out of
287) in the control group. There were no reported thromboembolic
events in the patients treated with EYLEA in the first six months
of the RVO studies.
- Serious adverse reactions related to the injection procedure
have occurred in <0.1% of intravitreal injections with EYLEA
including endophthalmitis and retinal detachment.
- The most common adverse reactions (≥5%) reported in patients
receiving EYLEA were conjunctival hemorrhage, eye pain, cataract,
vitreous detachment, vitreous floaters, and intraocular pressure
increased.
INDICATIONS
EYLEA® (aflibercept)
Injection 2 mg (0.05 mL) is indicated for the treatment of patients
with Neovascular (Wet) Age-related Macular Degeneration (AMD),
Macular Edema following Retinal Vein Occlusion (RVO), Diabetic
Macular Edema (DME), and Diabetic Retinopathy (DR).
DOSAGE AND ADMINISTRATION
Diabetic Macular Edema (DME) and Diabetic Retinopathy
(DR)
- The recommended dose for EYLEA is 2 mg (0.05 mL) administered
by intravitreal injection every 4 weeks (approximately every 28
days, monthly) for the first 5 injections followed by 2 mg (0.05
mL) via intravitreal injection once every 8 weeks (2 months).
- Although EYLEA may be dosed as frequently as 2 mg every 4 weeks
(approximately every 25 days, monthly), additional efficacy was not
demonstrated in most patients when EYLEA was dosed every 4 weeks
compared to every 8 weeks. Some patients may need every 4 week
(monthly) dosing after the first 20 weeks (5 months).
Neovascular (Wet) Age-Related Macular Degeneration
(AMD)
- The recommended dose for EYLEA is 2 mg (0.05 mL) administered
by intravitreal injection every 4 weeks (approximately every 28
days, monthly) for the first 3 months, followed by 2 mg (0.05 mL)
via intravitreal injection once every 8 weeks (2 months).
- Although EYLEA may be dosed as frequently as 2 mg every 4 weeks
(approximately every 25 days, monthly), additional efficacy was not
demonstrated in most patients when EYLEA was dosed every 4 weeks
compared to every 8 weeks. Some patients may need every 4 week
(monthly) dosing after the first 12 weeks (3 months).
- Although not as effective as the recommended every 8 week
dosing regimen, patients may also be treated with one dose every 12
weeks after one year of effective therapy. Patients should be
assessed regularly.
Macular Edema Following Retinal Vein Occlusion (RVO)
- The recommended dose for EYLEA is 2 mg (0.05 mL) administered
by intravitreal injection once every 4 weeks (approximately every
25 days, monthly).
For more information, please see 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 nine FDA-approved treatments and numerous product candidates in
development, almost 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, hematology,
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.
Regeneron Forward-Looking Statements and Use of Digital
Media
This press release includes forward-looking
statements that involve risks and uncertainties relating to future
events and the future performance of Regeneron Pharmaceuticals,
Inc. ("Regeneron" or the "Company"), and actual events or results
may differ materially from these forward-looking statements. Words
such as "anticipate," "expect," "intend," "plan," "believe,"
"seek," "estimate," variations of such words, and similar
expressions are intended to identify such forward-looking
statements, although not all forward-looking statements contain
these identifying words. These statements concern, and these
risks and uncertainties include, among others, the impact of
SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on
Regeneron's business and its employees, collaborators, and
suppliers and other third parties on which Regeneron relies,
Regeneron's and its collaborators' ability to continue to conduct
research and clinical programs, Regeneron's ability to manage its
supply chain, net product sales of products marketed or otherwise
commercialized by Regeneron and/or its collaborators (collectively,
"Regeneron's Products"), and the global economy; the nature,
timing, and possible success and therapeutic applications of
Regeneron's Products and product candidates being developed by
Regeneron and/or its collaborators (collectively, "Regeneron's
Product Candidates") and research and clinical programs now
underway or planned, including without limitation EYLEA®
(aflibercept) Injection; uncertainty of market acceptance and
commercial success of Regeneron's Products and Regeneron's Product
Candidates and the impact of studies (whether conducted by
Regeneron or others and whether mandated or voluntary), including
the study discussed in this press release, on the commercial
success of Regeneron's Products (such as EYLEA) and Regeneron's
Product Candidates; the likelihood, timing, and scope of possible
regulatory approval and commercial launch of Regeneron's Product
Candidates and new indications or dosing intervals for Regeneron's
Products, such as the 16-week dosing interval for EYLEA discussed
in this press release; safety issues resulting from the
administration of Regeneron's Products (such as EYLEA) and
Regeneron's Product Candidates in patients, including serious
complications or side effects in connection with the use of
Regeneron's Products and Regeneron's Product Candidates in clinical
trials; determinations by regulatory and administrative
governmental authorities which may delay or restrict Regeneron's
ability to continue to develop or commercialize Regeneron's
Products and Regeneron's Product Candidates; ongoing regulatory
obligations and oversight impacting Regeneron's Products, research
and clinical programs, and business, including those relating to
patient privacy; the availability and extent of reimbursement of
Regeneron's Products from third-party payers, including private
payer healthcare and insurance programs, health maintenance
organizations, pharmacy benefit management companies, and
government programs such as Medicare and Medicaid; coverage and
reimbursement determinations by such payers and new policies and
procedures adopted by such payers; competing drugs and product
candidates that may be superior to, or more cost effective than,
Regeneron's Products and Regeneron's Product Candidates; the extent
to which the results from the research and development programs
conducted by Regeneron and/or its collaborators may be replicated
in other studies and/or lead to advancement of product candidates
to clinical trials, therapeutic applications, or regulatory
approval; the ability of Regeneron to manufacture and manage supply
chains for multiple products and product candidates; the ability of
Regeneron's collaborators, suppliers, or other third parties (as
applicable) to perform manufacturing, filling, finishing,
packaging, labeling, distribution, and other steps related to
Regeneron's Products and Regeneron's Product Candidates;
unanticipated expenses; the costs of developing, producing, and
selling products; the ability of Regeneron to meet any of its
financial projections or guidance and changes to the assumptions
underlying those projections or guidance; the potential for any
license, collaboration, or supply agreement, including Regeneron's
agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries
Ltd. (or their respective affiliated companies, as applicable), to
be cancelled or terminated; and risks associated with intellectual
property of other parties and pending or future litigation relating
thereto (including without limitation the patent litigation and
other related proceedings relating to EYLEA, Dupixent®
(dupilumab), Praluent® (alirocumab), and
REGEN-COVTM (casirivimab with imdevimab)), other
litigation and other proceedings and government investigations
relating to the Company and/or its operations, the ultimate outcome
of any such proceedings and investigations, and the impact any of
the foregoing may have on Regeneron's business, prospects,
operating results, and financial condition. A more complete
description of these and other material risks can be found in
Regeneron's filings with the U.S. Securities and Exchange
Commission, including its Form 10-K for the year ended December 31, 2020. Any forward-looking
statements are made based on management's current beliefs and
judgment, and the reader is cautioned not to rely on any
forward-looking statements made by Regeneron. Regeneron does not
undertake any obligation to update (publicly or otherwise) any
forward-looking statement, including without limitation any
financial projection or guidance, whether as a result of new
information, future events, or otherwise.
Regeneron uses its media and investor relations website and
social media outlets to publish important information about the
Company, including information that may be deemed material to
investors. Financial and other information about Regeneron is
routinely posted and is accessible on Regeneron's media and
investor relations website (http://newsroom.regeneron.com) and its
Twitter feed (http://twitter.com/regeneron).
Contacts:
Media Relations
Taylor Ramsey
Tel: +1 (914) 409-2381
taylor.ramsey@regeneron.com
Investor Relations
Mark
Hudson
Tel: +1 (914) 355-0213
Mark.Hudson@regeneron.com
View original
content:http://www.prnewswire.com/news-releases/nih-sponsored-trial-finds-eylea-aflibercept-injection-reduced-vision-threatening-complications-by-68-after-two-years-in-diabetic-retinopathy-patients-301259081.html
SOURCE Regeneron Pharmaceuticals, Inc.