Aflibercept 8 mg Meets Primary Endpoints in Two Global Pivotal Trials for DME and wAMD, with a Vast Majority of Patients Maintained on 12- and 16-week Dosing Intervals

91% and 89% of diabetic macular edema (DME) patients were rapidly initiated and maintained on 12- and 16-week dosing intervals (without need for regimen modification) through week 48, respectively

79% and 77% of wet age-related macular degeneration (wAMD) patients were rapidly initiated and maintained on 12- and 16-week dosing intervals (without need for regimen modification) through week 48, respectively

Safety of aflibercept 8 mg consistent with the established safety profile of EYLEA® (aflibercept) Injection

TARRYTOWN, NY, USA I September 8, 2022 I Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the primary endpoints were met in two pivotal trials investigating novel aflibercept 8 mg with 12- and 16-week dosing regimens in patients with diabetic macular edema (DME) and wet age-related macular degeneration (wAMD). The PHOTON trial in DME and the PULSAR trial in wAMD both demonstrated that aflibercept 8 mg 12- and 16-week dosing regimens achieved non-inferiority in vision gains compared to the EYLEA 8-week dosing regimen. In these trials, the safety of aflibercept 8 mg was consistent with the established safety profile of EYLEA. Regeneron and Bayer will submit these data to regulatory authorities in countries around the world.

"These pivotal aflibercept 8 mg trials demonstrated that nearly 90% of patients with diabetic macular edema and almost 80% of patients with wet age-related macular degeneration were able to maintain a 16-week dosing regimen," said David Brown, M.D., FACS, Director of Research at Retina Consultants of Texas in the U.S. and a trial investigator. "These unprecedented durability data coupled with a safety profile consistent with that of EYLEA support aflibercept 8 mg as a potential new standard-of-care in these diseases."

"These groundbreaking results are excellent news for patients. These outcomes have shown that aflibercept 8 mg not only improved vision with less frequent injections, but also demonstrated a similar safety profile to EYLEA," said Jean-François Korobelnik, M.D., Ph.D., Professor of Ophthalmology and Head of the Department of Ophthalmology at University Hospital of Bordeaux in France and a trial investigator.

PHOTON (N=658) and PULSAR (N=1,009) are double-masked, active-controlled pivotal trials that are being conducted in multiple centers globally. At 48 weeks, >90% of patients in all dosing groups in both trials completed the treatment period with efficacy results as follows:

 

EYLEA

8-week regimen

aflibercept 8 mg

12-week regimen

aflibercept 8 mg

16-week regimen

PHOTON (DME) n=167 n=328 n=163
Mean observed BCVA improvement 9.2 letters 8.8 letters 7.9 letters
Least squares mean difference in BCVA improvement,
primary endpoint (non-inferiority p-value)*
 

-0.57

(p<0.0001)

-1.44

(p=0.0031)

Mean observed BCVA at 48 weeks 71.0 letters 72.6 letters 69.8 letters
Patients maintained on dosing interval (without need for
regimen modification)
  91 % 89 %
≥2-step DRSS improvement, key
secondary endpoint^
27 % 29 % 20 %
 
PULSAR (wAMD) n=336 n=335 n=338
Mean observed BCVA improvement 7.6 letters 6.7 letters 6.2 letters
Least squares mean difference in BCVA improvement,
primary endpoint (non-inferiority p-value)*
 

-0.97

(p=0.0009)

-1.14

(p=0.0011)

Mean observed BCVA at 48 weeks 66.5 letters 66.9 letters 66.3 letters
Patients maintained on dosing interval (without need for
regimen modification)
  79 % 77 %
Patients without fluid in central subfield at
16 weeks, key secondary endpoint
52 %

63 %

(one-sided superiority p=0.0002)

BCVA: best corrected visual acuity; DRSS: diabetic retinopathy severity scale; N/A: not applicable

*Non-inferiority (1-sided) p-values are for the difference in least squares mean compared to EYLEA with margin of 4 letters

^The aflibercept 8 mg 12-week group met the non-inferiority margin of 15%, while the 16-week group did not

The safety of aflibercept 8 mg was similar to EYLEA in both trials, and consistent with the well-established safety profile of EYLEA from previous clinical trials. In both trials, there were no new safety signals for aflibercept 8 mg and EYLEA, and no cases of retinal vasculitis, occlusive retinitis or endophthalmitis. Key safety results* were as follows:

 

EYLEA

8-week regimen

aflibercept 8 mg

12-week regimen

aflibercept 8 mg

16-week regimen

PHOTON (DME) n=167 n=328 n=163
Serious ocular adverse events 0.6 % 0.6 % 0.6 %
Intraocular inflammation 0.6 % 1.2 % 0 %
Serious non-ocular AEs 15.6 % 15.9 % 12.3 %
APTC events 3.6 % 2.4 % 3.7 %
Retinal vasculitis 0 % 0 % 0 %
Occlusive retinitis 0 % 0 % 0 %
Endophthalmitis 0 % 0 % 0 %
       
PULSAR (wet AMD) n=336 n=335 n=338
Serious ocular adverse events 0.6 % 1.8 % 1.5 %
Intraocular inflammation 0.6 % 1.2 % 0.3 %
Serious non-ocular AEs 13.7 % 10.1 % 9.5 %
APTC events 1.5 % 0.3 % 0.3 %
Retinal vasculitis 0 % 0 % 0 %
Occlusive retinitis 0 % 0 % 0 %
Endophthalmitis 0 % 0 % 0 %

APTC: antiplatelet trialists' collaboration

*Preliminary assessment as of data cutoff

"Over the last decade, EYLEA has become the standard-of-care for diabetic macular edema and wet age-related macular degeneration," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of aflibercept. "The results of these trials with our novel aflibercept 8 mg formulation demonstrated that a remarkably high percentage of patients were maintained on 12- and 16-week dosing intervals through week 48, suggesting aflibercept 8 mg has the potential to be as paradigm-changing as EYLEA."

Detailed efficacy and safety data from PHOTON and PULSAR are planned for presentation at an upcoming medical meeting.

Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG. In the U.S., Regeneron maintains exclusive rights to EYLEA and aflibercept 8 mg. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of EYLEA.

Aflibercept 8 mg is investigational, and its safety and efficacy have not been evaluated by any regulatory authority.

About the Aflibercept 8 mg Trial Program
In both PHOTON and PULSAR, patients with DME and wAMD were randomized into three treatment groups to receive either: aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or EYLEA every 8 weeks. Patients treated with aflibercept 8 mg in both trials had 3 initial monthly doses, and patients treated with EYLEA received 5 initial monthly doses in PHOTON and 3 in PULSAR. In the first year, patients in the aflibercept 8 mg groups could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression was observed. Intervals could not be extended until the second year of the study, with those results still to be assessed. Patients in all EYLEA groups maintained a fixed 8-week dosing regimen throughout their participation in the trials. The lead sponsors of the trials were Regeneron for PHOTON and Bayer for PULSAR.

About DME and wAMD
DME is a common complication in eyes of people living with diabetes. DME occurs when high levels of blood sugar lead to damaged blood vessels in the eye that leak fluid into the macula. This can lead to vision loss and, in some cases, blindness. Of the nearly 28 million American adults living with diabetes, an estimated 1.2 million have DME.

wAMD is a retinal disease that may affect people as they age. It occurs when abnormal blood vessels grow and leak fluid under the macula, the part of the eye responsible for sharp central vision and seeing fine detail. This fluid can damage and scar the macula, which can cause vision loss. An estimated 1.1 million Americans have wAMD, and this number is expected to double by 2050.

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).

For more information, please see full Prescribing Information.

About Regeneron 
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 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 more information, please visit www.Regeneron.com or follow @Regeneron on Twitter.

SOURCE: Regeneron Pharmaceuticals

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