TARRYTOWN, N.Y., Aug. 24, 2021 /PRNewswire/ --
Phase 3 trials in wet AMD and diabetic macular edema fully
recruited, with results expected in the second half of 2022
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)
today announced that an ongoing Phase 2 proof-of-concept trial
evaluating an investigational 8 mg dose of aflibercept met its
primary safety endpoint, with no new safety signals observed
compared to the currently-approved 2 mg dose of EYLEA®
(aflibercept) Injection in patients with wet age-related macular
degeneration (wet AMD). In this small trial involving 106 patients,
a higher proportion of patients in the aflibercept 8 mg group had
no retinal fluid (43.4%, n=23/53) compared to patients treated with
EYLEA 2 mg (26.4%, n=14/53) (p=0.067) at week 16, the primary
efficacy endpoint. At this timepoint patients had received three
initial doses (administered at weeks 0, 4 and 8), after which
dosing was extended.
Aflibercept 8 mg is currently being evaluated in two large Phase
3 trials in wet AMD and diabetic macular edema (DME), which are
expected to report results in the second half of 2022. The trials
will assess the safety and efficacy of aflibercept 8 mg for up to
two years, with visual acuity as the primary efficacy endpoint at
48 weeks, measured by the Early Treatment Diabetic Retinopathy
Study (ETDRS) Best Corrected Visual Acuity (BCVA). Both trials will
assess aflibercept 8 mg compared to EYLEA 2 mg, testing dosing
intervals of every 12 weeks and every 16 weeks.
"We are cautiously optimistic that these early data suggest that
a higher dose of aflibercept may potentially benefit patients with
wet AMD, and we look forward to Phase 3 data next year, which will
be crucial to understand its overall efficacy and safety," said
George D. Yancopoulos, M.D., Ph.D.,
President and Chief Scientific Officer of Regeneron. "Having worked
for nearly two decades in retinal disease, we know that large,
robust data sets are required to fully understand whether a
medicine can achieve three critical things: improved visual and
anatomic outcomes, convenient dosing, and a safety profile that is
consistent with EYLEA."
During the initial 16 weeks of the Phase 2 trial, adverse events
(AEs) in the study eye occurred in 17.0% (9 of 53) of aflibercept 8
mg patients and 22.6% (12 of 53) of EYLEA 2 mg patients. Serious
ocular AEs occurred in two patients overall, one in the aflibercept
8 mg group (retinal tear) and one in the EYLEA 2 mg group (visual
acuity reduced). There were no AEs of intraocular inflammation
(including occlusive retinal vasculitis), anti-platelet trialists'
collaboration (APTC)-defined arterial thromboembolic events or
deaths in either patient group.
Wet AMD is the leading cause of vision loss among people 50
years and older in the U.S. Existing anti-VEGF treatments including
EYLEA have helped change the course of disease for millions of
patients worldwide, and efforts to develop new medicines are
focused on further enhancing clinical effectiveness while extending
the time between treatment doses. This new, concentrated high-dose
aflibercept formulation enables a greater amount of medicine to be
administered with each treatment, potentially extending the time
between doses while retaining the efficacy and safety profile seen
with EYLEA 2 mg.
Aflibercept 8 mg is being jointly developed by Regeneron and
Bayer.
About the Phase 2 Trial
The Phase 2 randomized,
single-masked trial (NCT04126317) enrolled 106 treatment-naïve
patients with wet AMD. The trial was designed to investigate the
safety, efficacy and tolerability of high-dose aflibercept (8 mg)
compared to the existing approved dose of EYLEA (2 mg). Patients
were randomized into two groups, with one group receiving
aflibercept 8 mg (n=53) and the other group receiving EYLEA 2 mg
(n=53). Patients in both groups received three initial injections
(weeks 0, 4 and 8), before the primary endpoint was assessed at
week 16, after which dosing was extended to every 12 weeks, or more
frequently if required due to persistent or worsening disease.
Efficacy was assessed via the presence of retinal fluid in the
center subfield on optical coherence tomography (OCT) at this
timepoint. The trial will continue through week 44.
Trial participants were at least 50 years of age (mean: 77
years), baseline retinal thickness was 502.1 microns, and the BCVA
ETDRS letter score was between 24 to 78 in the study eye (mean: 59
letters).
About the Phase 3 Clinical Program
There are two ongoing pivotal trials to investigate the efficacy
and safety of aflibercept 8 mg versus EYLEA 2 mg. In DME,
Regeneron is sponsoring the Phase 2/3 multi-center, randomized,
double-masked PHOTON trial (NCT04429503). In wet AMD, Bayer is
sponsoring the Phase 3 multi-center, randomized, double-masked
PULSAR trial (NCT04423718) in treatment naïve patients. Across both
trials, patients are randomized into one of three treatment groups,
testing aflibercept 8 mg with dosing regimens at either 12- or
16-week intervals or EYLEA 2 mg with an 8-week dosing regimen.
EYLEA INDICATIONS AND IMPORTANT SAFETY INFORMATION
- 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.
- Patients may experience temporary visual disturbances after
intravitreal injection with EYLEA and the associated eye
examinations. Advise patients not to drive or use machinery until
visual function has recovered sufficiently.
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, hematologic
conditions, 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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SOURCE Regeneron Pharmaceuticals, Inc.