TARRYTOWN, N.Y., Feb. 11, 2022 /PRNewswire/ --
Trial met primary safety endpoint and no new safety signals
seen through week 44
Results favored aflibercept 8 mg in visual acuity, drying and
other anatomical measures through week 44
Phase 3 results in wet age-related macular degeneration and
diabetic macular edema expected in the second half of 2022
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today
announced results from its Phase 2 proof-of-concept trial
evaluating an investigational 8 mg high dose of aflibercept
compared to the currently-approved 2 mg dose of EYLEA®
(aflibercept) Injection in patients with wet age-related macular
degeneration (wet AMD). The results will be presented at the
Angiogenesis (Angiogenesis, Exudation, and Degeneration) 2022
annual meeting on Saturday, February
12.
As previously announced, more patients treated with aflibercept
8 mg had no retinal fluid at week 16, when the primary efficacy
endpoint was assessed. At this timepoint, 43% (n=23/53) had no
fluid in the macula compared to 26% for EYLEA (n=14/53) (p=0.0667);
and 51% (n=27) had no fluid in the center subfield compared to 34%
for EYLEA (n=18) (p=0.0770). At week 16, patients in both
treatment groups had received three initial doses (administered at
weeks 0, 4 and 8), after which dosing was extended to every 12
weeks. In new results presented for the first time, aflibercept 8
mg continued to show numeric improvements in anatomical and vision
outcomes compared to EYLEA through 44 weeks.
"These Phase 2 data in wet AMD demonstrate the exciting
potential for aflibercept 8 mg to maintain dryness and improve
vision compared to the standard-of-care EYLEA," said Dr.
David Brown, Director of Research at
Retina Consultants of Texas. "This
is the first time we have seen a promising trend towards sustained
improved vision over EYLEA in wet AMD. I look forward to seeing the
results of the Phase 3 program investigating extended dosing of
aflibercept 8 mg."
Eyes treated with aflibercept 8 mg were more likely to be dry in
the center subfield on optical coherence tomography (OCT) compared
to EYLEA at every timepoint measured throughout the trial after the
initial monthly dosing period. At week 44 when the trial ended, key
anatomical and vision changes included:
- 40% (n=21/53) of patients treated with aflibercept 8 mg did not
have fluid in the center subfield compared to 28% (n=15/53) of
patients treated with EYLEA (nominal p=0.2185).
- Twice as many patients treated with aflibercept 8 mg (32%,
n=17/53) had no macular fluid compared to patients treated with
EYLEA (15%, n=8/53) (nominal p=0.0395), as measured by spectral
domain OCT. Measuring macular fluid provides an evaluation of a
larger area of the retina compared to the center subfield and may
provide a better understanding of the anatomical effects of
treatment in wet AMD.
- 7.9 average letter improvement from baseline in the aflibercept
8 mg group, compared to 5.1 letters in the EYLEA group, as measured
by Early Treatment Diabetic Retinopathy Study (ETDRS) letters
(nominal p=0.1957).
- Nearly half (47%) of aflibercept 8 mg patients achieved at
least a 10-letter gain (2 lines on a vision test) and more than a
quarter (28%) achieved more than 15 letters (3 lines on a vision
test), compared to 35% and 18% for patients treated with EYLEA,
respectively.
Through 44 weeks, adverse events (AEs) in the study eye occurred
in 38% (n=20/53) of both aflibercept 8 mg and EYLEA patients. There
were no serious AEs of intraocular inflammation (including
occlusive retinal vasculitis), and no anti-platelet trialists'
collaboration (APTC)-defined arterial thromboembolic events. The
most common ocular AEs that occurred more frequently in the
aflibercept 8 mg group were vitreous detachment (4 aflibercept 8
mg, 2 EYLEA), conjunctival hemorrhage (3 aflibercept 8 mg, 2 EYLEA)
and retinal tear (2 aflibercept 8 mg, 0 EYLEA). There was one
patient death in the aflibercept 8 mg unrelated to treatment.
"After more than two decades of following the science in retinal
diseases, we are very proud of our legacy helping millions of
patients to retain or improve their vision with EYLEA, which has
set a very high bar for any new treatment," said George D. Yancopoulos, M.D., Ph.D., President
and Chief Scientific Officer at Regeneron. "The results of this
Phase 2 trial for aflibercept 8 mg are promising and we look
forward to seeing the results from the Phase 3 program, which we
hope will show that aflibercept 8 mg can deliver clinical outcomes
that, at a minimum, will be comparable to standard-of-care EYLEA,
but allow for extended dosing regimens."
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.
Aflibercept 8 mg is being jointly developed by Regeneron and
Bayer. This new, concentrated high-dose aflibercept formulation
enables a greater amount of medicine to be administered with each
treatment, and could potentially extend the time between doses
while retaining the efficacy and safety profile seen with EYLEA.
Aflibercept 8 mg is currently under clinical development and its
safety and efficacy have not been fully evaluated by any regulatory
authority.
About the Phase 2 Trial
The Phase 2 randomized,
single-masked CANDELA trial (NCT04126317) enrolled 106
treatment-naïve patients with wet AMD. The trial was designed to
investigate the safety, efficacy and tolerability of aflibercept 8
mg compared to the currently-approved 2 mg dose of EYLEA. Patients
were randomized into two groups, with one group receiving
aflibercept 8 mg (n=53) and the other group receiving EYLEA (n=53).
Patients in both groups received three initial intravitreal
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 at this timepoint.
Trial participants were at least 50 years of age (mean: 77
years), mean baseline retinal thickness was 502.1 microns, and the
best corrected visual acuity (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. In diabetic macular
edema (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 with an 8-week
dosing regimen.
IMPORTANT EYLEA SAFETY INFORMATION AND INDICATIONS
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).
CONTRAINDICATIONS
- EYLEA 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.
WARNINGS AND PRECAUTIONS
- 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.
ADVERSE REACTIONS
- 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 an
intravitreal injection with EYLEA and the associated eye
examinations. Advise patients not to drive or use machinery until
visual function has recovered sufficiently.
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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