- No indication that drug product or manufacturing issues contributed to rare events of retinal vasculitis
- Confirmed seven total events of non-occlusive/occlusive retinal vasculitis since launch; more than 68,000 SYFOVRE vials distributed to date
- Zero events were reported in clinical trials, following more than 23,000 clinical trial injections to date
WALTHAM, MA, USA I July 29, 2023 I Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) (“the Company”) today provided an update on its review of rare events of retinal vasculitis reported in real-world treatment with SYFOVRE® (pegcetacoplan injection) for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
“The safety of patients has always been – and continues to be – our top priority at Apellis,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer of Apellis. “Following 68,000 commercial vials distributed and 23,000 clinical trial injections to date, these events continue to be very rare. Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events. We will continue to collaborate with the retina community to deliver a safe, effective treatment for GA and look forward to sharing long-term clinical data on SYFOVRE tomorrow at the ASRS Annual Scientific Meeting.”
Apellis has been conducting a thorough evaluation following these reported events, including a review of the SYFOVRE manufacturing process and drug product and of the safety data from the Company’s Phase 3 clinical trials of SYFOVRE. There were no changes in the formulation of the product between Phase 3 clinical trials and commercial supply.
Based on this review, there is no indication that drug product or manufacturing issues contributed to these events, and there were no new safety findings in the clinical trials upon secondary review. Specifically:
- No manufacturing related issues impacting product quality were identified
- No quality issues and no contaminants (e.g., endotoxins) were discovered
- No single manufacturing lot was implicated
- No indication of drug related immunogenicity was observed in the clinical trial data
- Zero events of retinal vasculitis were reported by investigators or identified by an independent reading center in the Phase 3 clinical trials. In addition:
- Apellis re-reviewed all intraocular inflammation (IOI) cases and confirmed no vasculitis events
- External retina/uveitis specialists re-reviewed all severe IOI cases and further confirmed no vasculitis events
Apellis is working closely with the retina community as it continues to investigate potential contributing factors and plans to continue to provide updates.
Apellis also provided an update on the events of retinal vasculitis reported to date:
- Since launch, Apellis has in total seven confirmed events of retinal vasculitis (4 occlusive, 3 non-occlusive) as determined by Apellis’ internal safety committee and external retina/uveitis specialists. Two of these events followed injections in April, two in May, and three in June.
- Apellis is also evaluating one reported event of retinal vasculitis, which the Company has not confirmed.
Apellis can only review and confirm cases that have been reported directly to the Company and will continue to submit all reported adverse events to the U.S. Food and Drug Administration (FDA) consistent with reporting guidelines for drug manufacturers.
As of July 29, 2023, more than 68,000 vials of SYFOVRE have been distributed since FDA approval, including commercial vials shipped and sample vials distributed to physician practices. In addition, more than 23,000 SYFOVRE injections have been administered in clinical trials to date.
Seven oral presentations on SYFOVRE and GA will be presented at the American Society of Retina Specialists (ASRS) Annual Scientific Meeting which is being held July 28 to August 1 in Seattle. Highlights will include new 30-month safety and efficacy data of SYFOVRE in patients with GA from the GALE long-term extension study.
SYFOVRE was approved by the FDA on February 17, 2023 based on positive results from the Phase 3 OAKS and DERBY studies at 24 months across a broad and clinically diverse population of more than 1,200 patients.
About the GALE Long-Term Extension Study
GALE (n=792) is a Phase 3, multicenter, open-label, extension study to evaluate the long-term efficacy and safety of SYFOVRE® (pegcetacoplan injection) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The objectives of the study are to evaluate the long-term incidence and severity of ocular and systemic treatment emergent adverse events as well as change in the total area of GA lesions as measured by fundus autofluorescence. More than 80-percent of participants who completed the OAKS and DERBY studies entered the GALE study.
About the Phase 3 OAKS and DERBY Studies
OAKS (n=637) and DERBY (n=621) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of SYFOVRE® (pegcetacoplan injection) with sham injections across a broad and heterogenous population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The studies evaluated the efficacy of monthly and every-other-month SYFOVRE in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence. In Phase 3 studies at 24 months, both every-other-month and monthly SYFOVRE reduced GA lesion growth with increasing effects over time and showed a well-demonstrated safety profile.
About Geographic Atrophy (GA)
Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a leading cause of blindness worldwide, impacting more than one million Americans and five million people worldwide.1,2 It is a progressive and irreversible disease caused by the growth of lesions, which destroy the retinal cells responsible for vision. The vision loss caused by GA severely impairs independence and quality of life by making it difficult to participate in daily activities. On average, it takes only 2.5 years for GA lesions to start impacting the fovea, which is responsible for central vision.3
About SYFOVRE® (pegcetacoplan injection)
SYFOVRE® (pegcetacoplan injection) is the first and only approved therapy for geographic atrophy (GA). By targeting C3, SYFOVRE is designed to provide comprehensive control of the complement cascade, part of the body’s immune system. SYFOVRE is approved in the United States for the treatment of GA secondary to age-related macular degeneration.
Marketing applications are currently under review with five regulatory agencies worldwide. A decision in the EU is expected in early 2024, and decisions in Canada, Australia, Switzerland, and the United Kingdom are expected in the first half of 2024.
U.S. Important Safety Information for SYFOVRE® (pegcetacoplan injection)
CONTRAINDICATIONS
- SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation
WARNINGS AND PRECAUTIONS
- Endophthalmitis and Retinal Detachments
- Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
- Neovascular AMD
- In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
- Intraocular Inflammation
- In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
- Increased Intraocular Pressure
- Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.
ADVERSE REACTIONS
- Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.
- To report suspected adverse reactions, contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see accompanying full Prescribing Information for more information.
About Apellis
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first and only therapy for geographic atrophy, a leading cause of blindness around the world. With nearly a dozen clinical and pre-clinical programs underway, we believe we have only begun to unlock the potential of targeting C3 across many serious diseases. For more information, please visit http://apellis.com or follow us on Twitter and LinkedIn.
1Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta analysis. Ophthalmology 2012;119:571–580.
2Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.
3 Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
SOURCE: Apellis Pharmaceuticals
Post Views: 453
- No indication that drug product or manufacturing issues contributed to rare events of retinal vasculitis
- Confirmed seven total events of non-occlusive/occlusive retinal vasculitis since launch; more than 68,000 SYFOVRE vials distributed to date
- Zero events were reported in clinical trials, following more than 23,000 clinical trial injections to date
WALTHAM, MA, USA I July 29, 2023 I Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) (“the Company”) today provided an update on its review of rare events of retinal vasculitis reported in real-world treatment with SYFOVRE® (pegcetacoplan injection) for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
“The safety of patients has always been – and continues to be – our top priority at Apellis,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer of Apellis. “Following 68,000 commercial vials distributed and 23,000 clinical trial injections to date, these events continue to be very rare. Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events. We will continue to collaborate with the retina community to deliver a safe, effective treatment for GA and look forward to sharing long-term clinical data on SYFOVRE tomorrow at the ASRS Annual Scientific Meeting.”
Apellis has been conducting a thorough evaluation following these reported events, including a review of the SYFOVRE manufacturing process and drug product and of the safety data from the Company’s Phase 3 clinical trials of SYFOVRE. There were no changes in the formulation of the product between Phase 3 clinical trials and commercial supply.
Based on this review, there is no indication that drug product or manufacturing issues contributed to these events, and there were no new safety findings in the clinical trials upon secondary review. Specifically:
- No manufacturing related issues impacting product quality were identified
- No quality issues and no contaminants (e.g., endotoxins) were discovered
- No single manufacturing lot was implicated
- No indication of drug related immunogenicity was observed in the clinical trial data
- Zero events of retinal vasculitis were reported by investigators or identified by an independent reading center in the Phase 3 clinical trials. In addition:
- Apellis re-reviewed all intraocular inflammation (IOI) cases and confirmed no vasculitis events
- External retina/uveitis specialists re-reviewed all severe IOI cases and further confirmed no vasculitis events
Apellis is working closely with the retina community as it continues to investigate potential contributing factors and plans to continue to provide updates.
Apellis also provided an update on the events of retinal vasculitis reported to date:
- Since launch, Apellis has in total seven confirmed events of retinal vasculitis (4 occlusive, 3 non-occlusive) as determined by Apellis’ internal safety committee and external retina/uveitis specialists. Two of these events followed injections in April, two in May, and three in June.
- Apellis is also evaluating one reported event of retinal vasculitis, which the Company has not confirmed.
Apellis can only review and confirm cases that have been reported directly to the Company and will continue to submit all reported adverse events to the U.S. Food and Drug Administration (FDA) consistent with reporting guidelines for drug manufacturers.
As of July 29, 2023, more than 68,000 vials of SYFOVRE have been distributed since FDA approval, including commercial vials shipped and sample vials distributed to physician practices. In addition, more than 23,000 SYFOVRE injections have been administered in clinical trials to date.
Seven oral presentations on SYFOVRE and GA will be presented at the American Society of Retina Specialists (ASRS) Annual Scientific Meeting which is being held July 28 to August 1 in Seattle. Highlights will include new 30-month safety and efficacy data of SYFOVRE in patients with GA from the GALE long-term extension study.
SYFOVRE was approved by the FDA on February 17, 2023 based on positive results from the Phase 3 OAKS and DERBY studies at 24 months across a broad and clinically diverse population of more than 1,200 patients.
About the GALE Long-Term Extension Study
GALE (n=792) is a Phase 3, multicenter, open-label, extension study to evaluate the long-term efficacy and safety of SYFOVRE® (pegcetacoplan injection) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The objectives of the study are to evaluate the long-term incidence and severity of ocular and systemic treatment emergent adverse events as well as change in the total area of GA lesions as measured by fundus autofluorescence. More than 80-percent of participants who completed the OAKS and DERBY studies entered the GALE study.
About the Phase 3 OAKS and DERBY Studies
OAKS (n=637) and DERBY (n=621) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of SYFOVRE® (pegcetacoplan injection) with sham injections across a broad and heterogenous population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The studies evaluated the efficacy of monthly and every-other-month SYFOVRE in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence. In Phase 3 studies at 24 months, both every-other-month and monthly SYFOVRE reduced GA lesion growth with increasing effects over time and showed a well-demonstrated safety profile.
About Geographic Atrophy (GA)
Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a leading cause of blindness worldwide, impacting more than one million Americans and five million people worldwide.1,2 It is a progressive and irreversible disease caused by the growth of lesions, which destroy the retinal cells responsible for vision. The vision loss caused by GA severely impairs independence and quality of life by making it difficult to participate in daily activities. On average, it takes only 2.5 years for GA lesions to start impacting the fovea, which is responsible for central vision.3
About SYFOVRE® (pegcetacoplan injection)
SYFOVRE® (pegcetacoplan injection) is the first and only approved therapy for geographic atrophy (GA). By targeting C3, SYFOVRE is designed to provide comprehensive control of the complement cascade, part of the body’s immune system. SYFOVRE is approved in the United States for the treatment of GA secondary to age-related macular degeneration.
Marketing applications are currently under review with five regulatory agencies worldwide. A decision in the EU is expected in early 2024, and decisions in Canada, Australia, Switzerland, and the United Kingdom are expected in the first half of 2024.
U.S. Important Safety Information for SYFOVRE® (pegcetacoplan injection)
CONTRAINDICATIONS
- SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation
WARNINGS AND PRECAUTIONS
- Endophthalmitis and Retinal Detachments
- Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
- Neovascular AMD
- In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
- Intraocular Inflammation
- In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
- Increased Intraocular Pressure
- Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.
ADVERSE REACTIONS
- Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.
- To report suspected adverse reactions, contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see accompanying full Prescribing Information for more information.
About Apellis
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first and only therapy for geographic atrophy, a leading cause of blindness around the world. With nearly a dozen clinical and pre-clinical programs underway, we believe we have only begun to unlock the potential of targeting C3 across many serious diseases. For more information, please visit http://apellis.com or follow us on Twitter and LinkedIn.
1Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta analysis. Ophthalmology 2012;119:571–580.
2Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.
3 Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
SOURCE: Apellis Pharmaceuticals
Post Views: 453
