TARRYTOWN, N.Y., Feb. 8, 2020 /PRNewswire/ --
New data highlight importance of proactive EYLEA treatment as
more than half of untreated patients in PANORAMA developed
vision-threatening events over two years
High-dose aflibercept development program underway with Phase
3 trials planned for 2020
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)
announced positive two-year results from the Phase 3 PANORAMA trial
evaluating EYLEA® (aflibercept) Injection 2 mg (0.05 mL)
in patients with moderately severe to severe non-proliferative
diabetic retinopathy (NPDR). The data were presented today for the
first time at the Angiogenesis, Exudation, and Degeneration 2020
meeting in Miami, Florida.
The two-year pre-specified exploratory data demonstrate that
untreated moderately severe and severe NPDR can lead to
vision-threatening events, which includes vision-threatening
complications (VTCs; proliferative diabetic retinopathy or anterior
segment neovascularization) and center-involved diabetic macular
edema (CI-DME). Based on a Kaplan-Meier analysis, more than half
(58%) of patients in the untreated sham arm developed a VTC or
CI-DME within two years of entering the trial, while EYLEA
treatment was shown to reduce the likelihood of these
vision-threatening events by at least 75% (nominal
p<0.0001).
"These data reinforce that regular EYLEA treatment can be highly
effective at reducing the risk of new vision-threatening events
among patients with moderately severe to severe non-proliferative
diabetic retinopathy," said Charles C.
Wykoff, M.D., Ph.D., PANORAMA investigator, retina surgeon
and ophthalmologist with Retina Consultants of Houston. "The PANORAMA trial shows that more
than half of all untreated patients developed vision-threatening
events over two years, underscoring the value of treating patients
proactively and regularly."
The two-year results also showed a greater benefit for EYLEA
patients treated at regular intervals compared to patients who
received EYLEA treatment less frequently. Per the protocol, the
group of trial patients who received EYLEA every 8 weeks in the
first year were switched to receive it when their doctor determined
they needed it (called pro re nata, or PRN) in the second year
(i.e., the 8-week/PRN group). The proportion of these patients with
a >2-step improvement from
baseline in Diabetic Retinopathy Severity Scale (DRSS) scores
decreased in the second year (80% improvement at 52 weeks and 50%
at 100 weeks).* By comparison, in patients who continued to receive
EYLEA every 16 weeks (i.e., the 16-week group), the >2-step DRSS
scores remained consistent (65% at 52 weeks vs. 62% at 100 weeks).*
In the second year, patients received an average of 1.8 injections
in the 8-week/PRN group (out of a possible 6); a review of data
from the independent reading center of investigator PRN
decisions suggests that some of these patients may have been
under-dosed based on the protocol rules of the trial.
Patients in the 16-week group received 2.6 injections (out of
a possible 3) in the second year.
During the 2-year PANORAMA trial, adverse events were consistent
with the known profile of EYLEA. Serious ocular adverse events in
the study eye occurred in 2% and 0% of the EYLEA 8-week/PRN and
16-week groups, respectively, and 2% of patients in the sham group.
Ocular inflammation occurred in 2% and 1% of patients in the EYLEA
treatment groups, respectively, and 1% of patients in the sham
group. Anti-platelet trialists' collaboration (APTC)-defined
arterial thromboembolic treatment emergent events occurred in 3%
and 6% of patients in the EYLEA treatment groups, respectively, and
5% of patients in the sham group.
*p<0.0001 at 52 weeks; nominal p<0.0001 at 100 weeks, as
all prespecified endpoints at 100 weeks are considered
exploratory.
High-Dose Aflibercept Update
Also presented
today was the rationale for high-dose (8 mg) aflibercept clinical
trials. A Phase 2 trial (CANDELA) evaluating high-dose aflibercept
in wet age-related macular degeneration (wet AMD) is currently
enrolling. Phase 3 trials planned to start in 2020 in wet AMD
(PULSAR, sponsored by Bayer) and DME (PHOTON, sponsored by
Regeneron) will evaluate dosing intervals of 12 weeks and
longer.
"Through millions of injections and eight pivotal Phase 3
trials, EYLEA has built a substantial body of evidence and safety
profile. High-dose aflibercept will hopefully build on this
standard-of-care therapy and represents our ongoing commitment to
ophthalmologic research and development," said George D. Yancopoulos, M.D., Ph.D., President
and Chief Scientific Officer at Regeneron. "We are eager to explore
the potential of high-dose aflibercept to deliver sustained vision
gains and extended duration of action in patients with wet AMD and
DME."
The potential use of high-dose aflibercept is currently under
clinical development and the safety and efficacy for this use have
not been fully evaluated by any regulatory authority.
About the PANORAMA trial
The U.S. Food and Drug
Administration (FDA) approval of EYLEA to treat diabetic
retinopathy was based on six-month and one-year results from
PANORAMA, a randomized, multi-center, controlled Phase 3 trial that
enrolled 402 patients and was designed to investigate EYLEA for the
improvement of moderately severe to severe NPDR without DME,
compared to sham injection. PANORAMA is the first prospective trial
to study whether vascular endothelial growth factor (VEGF)
inhibition can also help prevent worsening disease in patients with
NPDR without DME.
Details on trial design included:
- Three treatment arms – an observational sham injection
group and two EYLEA treatment groups. EYLEA was dosed every eight
weeks (following five initial monthly doses) or every 16 weeks
(following three initial monthly doses and one 8-week interval). At
week 52, the 8-week interval group switched to as needed (PRN)
dosing determined by the investigator. All patients were followed
to week 100.
- Primary endpoint – the primary endpoint was the
proportion of patients who experienced a 2-step or greater
improvement in the DRSS score from baseline for the combined EYLEA
treatment groups at week 24, and for each EYLEA treatment group
separately (every 8-week group and every 16-week group) at week 52.
The DRSS is a systematic grading scale to assess diabetic
retinopathy severity based on photographs of the retina.
- Secondary endpoints – the secondary endpoints included
assessment of whether EYLEA reduced the risk of worsening disease –
specifically progression to PDR (including anterior segment
neovascularization [ASNV]) or the development of CI-DME – as well
as change in visual acuity, through week 52.
- Exploratory endpoints – all prespecified endpoints at
week 100 (year two) are considered exploratory.
One-year results from PANORAMA were previously reported in
October 2018 and February 2019. A separate ongoing trial sponsored
by the Diabetic Retinopathy Clinical Research Network known as
Protocol W is also evaluating EYLEA for the treatment of NPDR in
patients without DME.
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 a stage of the
disease in which abnormal blood vessels grow onto the surface of
the retina and potentially cause severe, vision-threatening
complications such as proliferative diabetic retinopathy and
anterior segment neovascularization.
DME can occur at any stage of diabetic retinopathy 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 diabetic retinopathy without DME.
About EYLEA® (aflibercept)
Injection
EYLEA® (aflibercept) Injection is a
vascular endothelial growth factor (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 number one prescribed
FDA-approved anti-VEGF treatment across its approved indications
and is supported by a robust body of research that includes seven
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 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.
Regeneron Forward-Looking Statements and Use of Digital
Media
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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,"
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success of Regeneron's Products and product candidates (such as
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