Aflibercept 8 mg Two-Year Results from Pivotal PHOTON Trial in Diabetic Macular Edema Presented at ASRS

89% and 84% of patients were maintained on ≥12- and ≥16-week dosing intervals, respectively, throughout the two-year period, while sustaining their vision and anatomic improvements

At two years, 44% of patients met the criteria for ≥20-week dosing intervals, including 27% who were eligible for 24-week dosing intervals

TARRYTOWN, N.Y., July 29, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the first presentation of positive two-year (96 weeks) results from the pivotal PHOTON trial investigating aflibercept 8 mg with 12- and 16-week dosing regimens, compared to EYLEA^® (aflibercept) Injection, in patients with diabetic macular edema (DME). The results were presented at the American Society of Retina Specialists (ASRS) annual meeting.

“At two years, the PHOTON trial demonstrates the substantial impact aflibercept 8 mg could have in reducing treatment burden for patients with diabetic macular edema,” said Diana V. Do, MD, Professor of Ophthalmology and Vice Chair for Clinical Affairs at the Byers Eye Institute, Stanford University and a trial investigator. “Maintaining two years of vision and anatomic improvements with as few as three or four injections per year, while not compromising safety, is impressive and could make a meaningful difference in the lives of the patients we treat.”

PHOTON (N=658) is a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept 8 mg extended dosing intervals compared to EYLEA. Patients receiving aflibercept 8 mg were initially randomized to either 12- (n=328) or 16-week (n=163) dosing intervals (after three initial monthly doses) compared to an 8-week dosing regimen for EYLEA (n=167) after five initial monthly doses. During the trial, patients receiving aflibercept 8 mg could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Patients were only able to extend their dosing intervals in the second year by 4-week increments up to 24-weeks, if pre-specified criteria were met.

The PHOTON trial met its primary endpoint last year with aflibercept 8 mg patients achieving clinically equivalent vision gains to EYLEA, with approximately 90% maintaining 12- and 16-week dosing regimens through the first year. Through two years, the mean number of injections administered were 9.5 for the 12-week aflibercept 8 mg group, 7.8 for the 16-week aflibercept 8 mg group, and 13.8 for the EYLEA group, with the vast majority of aflibercept 8 mg patients maintaining extended dosing intervals as first shared in June 2023:

• 89% of patients maintained ≥12-week dosing intervals, compared to 93% through one year
• 84% maintained ≥16-week dosing intervals, compared to 89% maintaining a 16-week dosing interval through one year, among those randomized at baseline to a 16-week dosing interval
• 44% met the criteria for ≥20-week dosing intervals at week 96, including 17% and 27% who were eligible for 20- and 24-week dosing intervals, respectively
  

The safety of aflibercept 8 mg continued to be similar to EYLEA through two years and remained consistent with the known safety profile of EYLEA from previous clinical trials for DME. Ocular treatment emergent adverse events (TEAE) occurring in 5% of patients in any treatment group, in decreasing frequency, were cataract, vitreous floaters and conjunctival hemorrhage. There were no cases of retinal vasculitis, occlusive retinitis or endophthalmitis. The rate of intraocular inflammation was 1.2% for both the EYLEA and aflibercept 8 mg groups. Anti-platelet trialists' collaboration-defined arterial thromboembolic TEAEs occurred in 7.2% of patients treated with EYLEA and 6.7% of patients treated with aflibercept 8 mg.

The full ASRS presentation is available on the Regeneron website. The two-year data from the pivotal PULSAR trial for aflibercept 8 mg in wet age-related macular degeneration (wAMD) are expected in the third quarter of 2023.

Aflibercept 8 mg is investigational, and its safety and efficacy have not been fully evaluated by any regulatory authority. Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG, with Regeneron sponsoring the PHOTON trial. 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 and aflibercept 8 mg following any regulatory approvals.

About the Aflibercept 8 mg Clinical Trial Program
PULSAR in wAMD and PHOTON in DME are double-masked, active-controlled pivotal trials that are being conducted in multiple centers globally. In both trials, patients were randomized into 3 treatment groups to receive either: aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or EYLEA every 8 weeks. The lead sponsors of the trials were Bayer for PULSAR and Regeneron for PHOTON.

Patients treated with aflibercept 8 mg in both trials had 3 initial monthly doses, and patients treated with EYLEA received 3 initial doses in PULSAR and 5 in PHOTON. During the trial, 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 were observed. Intervals could not be extended until the second year of the study. Patients in all EYLEA groups maintained a fixed 8-week dosing regimen throughout their participation in the trials.

About DME
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.

About Ophthalmology at Regeneron
At Regeneron, we relentlessly pursue groundbreaking innovations in eye care science to help maintain the eye health of the millions of Americans impacted by vision-threatening conditions. Over a decade ago, our breakthrough scientific research resulted in the development of EYLEA, a vascular endothelial growth factor (VEGF) inhibitor designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels in the eye. EYLEA has since brought fundamental change to the retinal disease treatment landscape and is supported by a robust body of research that includes eight pivotal Phase 3 trials, 11 years of real-world experience, and more than 64 million EYLEA injections globally.

Regeneron continues to advance our anti-angiogenesis expertise with new solutions with the aim of offering optimal flexibility for a broad group of patients and eye care professionals. This includes aflibercept 8 mg, which is being developed with the aim of extending the time between injections, while maintaining the vision gains, anatomic benefits and safety previously observed with EYLEA.

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), Diabetic Retinopathy (DR) and Retinopathy of Prematurity (ROP) (0.4 mg [0.01 mL]).

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 and/or caregivers should be instructed to report any signs and/or 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.
• In infants with ROP, reactivation of abnormal angiogenesis and tortuosity may occur following treatment with EYLEA. Infants should be monitored closely after injection with EYLEA until retinal vascularization has completed or until the examiner is assured that reactivation of ROP will not occur. Treatment with EYLEA will necessitate extended periods of ROP monitoring and additional EYLEA injections and/or laser treatments may be necessary.
• 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.
• In pre-term infants with ROP receiving EYLEA the most common adverse reactions (≥4%) reported were retinal detachment, conjunctival hemorrhage, and intraocular pressure increased. Adverse reactions established for adult indications are considered applicable to pre-term infants with ROP, though not all were observed in the clinical studies.
• 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, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to 9 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, 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.

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