Ranibizumab (Genentech)

The FDA has accepted Roche's application for its eye implant Susvimo to treat patients with diabetic retinopathy and diabetic macular edema. After storming the market with its longer-acting macular degeneration shot Vabysmo, Roche is laying the groundwork to expand the reach of its other eye disease innovation—refillable implant Susvimo. On Thursday, Roche not only announced that the FDA has accepted its application for Susvimo to treat diabetic retinopathy (DR) and diabetic macular edema (DME), the company also unveiled results that demonstrate Susvimo’s durability against both disorders. Data from the phase 3 Pavilion (DR) and Pagoda (DME) studies show that Susvimo sustained its efficacy for two years while maintaining its safety profile. Roche’s subsidiary Genentech shared the results Thursday at the American Society of retina Specialists (ASRS) annual meeting in Stockholm, Sweden. On Wednesday at the ASRS, Genentech also presented results from a Vabysmo study, which showed that after four years of treatment more than 90% of patients had no sign of DME and that nearly 80% were able to extend their dosing intervals to every three to four months. Vabysmo, which was approved in 2022 to treat wet-age-related macular edema (AMD) and DME, entered the market as a longer-acting competition to Regeneron and Bayer’s Eylea. The original Eylea has a staying power of two months until the companies answered in August 2023 with a high-dose version that can be given up to once every four months.  As for Susvimo, the unique product appears back on track. It was initially approved for AMD in October 2021 but was recalled by the company a year later because of a manufacturing issue. Earlier this month, Roche said that the FDA had signed off on its re-launch. In the long-term results of the Pavilion study, DR patients—who were refilled with Susvimo every nine months through a span of two years—maintained the progress they showed during their first year of treatment. Additionally, 80% of patients achieved a two-step or greater improvement in the 12-step diabetic retinopathy severity scale (DRSS), the primary tool used to measure the progression of the disorder. In the long-term results of the Pagoda study, DME patients—who received refills of Susvimo every six months for a span of two years—continued to maintain the improvements seen in their vision through one year, which equated to gaining two more lines on an eye chart. Additionally, 95% of those on Susvimo did not need additional treatment with supplemental injections. “These efficacy and safety results demonstrate that Susvimo can deliver robust vision outcomes over two years for people with diabetic eye diseases that can cause vision loss,” Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of global product development, said in a release. “If approved by the FDA, Susvimo could bring a new treatment paradigm for diabetic eye diseases.” A large market awaits if Susvimo can earn its label expansion. In the United States, there are 7.7 million with DR. The disorder can progress into DME, which affects 750,000 in the U.S. The FDA-accepted application was based on the one-year results of the Pavilion and Pagoda studies. While uptake of Susvimo was slow during its initial launch, the same can’t be said of Vabysmo, which generated sales of 847 million Swiss francs ($933 million) in the first quarter for a 108% year-over-year increase. Meanwhile, Regeneron tallied worldwide sales of Eylea at $2.25 billion, which was a 1% decline from the first quarter of 2023.   Earlier this month, the FDA gave a thumbs up for Vabysmo to be provided in a prefilled syringe. The nod gives doctors a more convenient, ready-to-use alternative to drawing the medicine from a vial.

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today two-year data from the Phase III Pagoda and Pavilion studies evaluating Susvimo ® (ranibizumab injection) 100 mg/mL for the treatment of diabetic macular edema (DME) and diabetic retinopathy (DR), respectively, the two leading causes of vision loss in adults with diabetes. Susvimo is the first and only refillable eye implant that provides continuous delivery of a customized formulation of ranibizumab via the Port Delivery Platform. The results build on the primary one-year analyses of the Pagoda and Pavilion studies, with Susvimo demonstrating sustained efficacy over two years and safety consistent with the known safety profile for Susvimo in people with DME and DR. Detailed results were presented at the American Society of Retina Specialists (ASRS) 2024 Annual Meeting in Stockholm, Sweden. Additionally, the U.S. Food and Drug Administration (FDA) has accepted Genentech’s supplemental Biologics License Application (sBLA) for Susvimo for the treatment of DME and DR. The filing acceptance is based on the one-year results from the Phase III Pagoda and Pavilion studies, which showed that both studies met their primary endpoint. To date, Susvimo is approved in the U.S. for the treatment of wet, or neovascular, age-related macular degeneration (AMD). “These efficacy and safety results demonstrate that Susvimo can deliver robust vision outcomes over two years for people with diabetic eye diseases that can cause vision loss,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “If approved by the FDA, Susvimo could bring a new treatment paradigm for diabetic eye diseases. We hope to bring this option to people with diabetic macular edema and diabetic retinopathy as soon as possible to help maintain their vision and potentially their independence.” One-year primary data supporting U.S. sBLA in DME and DR Treatment for DME typically involves regular eye injections every one to four months. In Pagoda, people with DME who received Susvimo refilled every six months achieved non-inferior visual acuity gains compared with those receiving monthly 0.5 mg ranibizumab intravitreal injections. Approximately 95% of patients treated with Susvimo did not need additional treatment with supplemental injections during the primary analyses study period (64 weeks). In Pavilion, people with DR who received Susvimo refilled every nine months achieved superior improvements on the Diabetic Retinopathy Severity Scale (DRSS) compared with participants under monthly clinical observation. No individuals treated with Susvimo needed additional treatment with supplemental injections during the primary analyses study period (52 weeks), compared to 60% in the control arm. Two-year Pagoda and Pavilion results presented at ASRS In Pagoda, people with DME receiving Susvimo refilled every six months through approximately two years (112 weeks) continued to maintain improvements in vision gains seen at one year (9.8 eye chart letters). A gain of 9.8 eye chart letters is similar to gaining two more lines on an eye chart. Approximately 95% of individuals did not need additional treatment with supplemental injections. Anatomically, Susvimo showed sustained improvements in central subfield thickness (CST) through week 112. Reduction in CST, a measure of retinal drying, is an indicator of swelling from fluid in the back of the eye caused by unstable, leaky blood vessels. The safety data were consistent with the known safety profile for Susvimo in people with DME, with no new safety signals observed. In people treated with Susvimo, no cases of endophthalmitis were reported up to one year and the rate of endophthalmitis through week 112 was 0.7%, compared to 0.8% in the control arm. Refills of Susvimo were resumed in affected participants after successful resolution of endophthalmitis. In Pavilion, people with DR receiving Susvimo refilled every nine months through approximately two years (100 weeks) maintained DRSS improvements seen at one year. Specifically, at week 100, 80% of Susvimo participants achieved a two-step or greater improvement on the DRSS from pre-implant baseline, and participants who received Susvimo from week 64 either maintained or improved their DRSS score from pre-implant baseline. A two-step or greater improvement in the DRSS is a clinically relevant measure of the decrease in risk for developing vision-threatening complications secondary to diabetes. Approximately 98% of participants treated with Susvimo did not need additional treatment with supplemental injections. The safety data were consistent with the known safety profile for Susvimo in people with DR, with no new safety signals observed. In people treated with Susvimo, no cases of endophthalmitis were reported up to one year and the rate of endophthalmitis through week 100 was 0.8%. One participant with DR developed endophthalmitis and continued receiving treatment with Susvimo refills after successful resolution. Genentech is committed to helping people access the medicines they are prescribed and offers comprehensive services for people prescribed Susvimo to help minimize barriers to access and reimbursement. Patients can call 833-EYE-GENE for more information. For people who qualify, Genentech offers patient assistance programs through Genentech Access Solutions. More information is also available at (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com . Visit https://www.Susvimo.com for additional information. About Diabetic Macular Edema (DME) Affecting approximately 750,000 people in the U.S., diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated. DME occurs when damaged blood vessels in the retina leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving. The number of people with DME is expected to grow as the prevalence of diabetes increases. About Diabetic Retinopathy (DR) Diabetic retinopathy (DR) affects approximately 7.7 million Americans and 93 million people globally, accounting for almost 5% of all cases of blindness. DR can lead to the development of DME, which is a leading cause of vision loss, affecting around 21 million adults worldwide. The longer a person has diabetes, especially if it is poorly controlled, the higher the risk of developing diabetic retinopathy and vision loss. Diabetic retinopathy occurs when blood vessels in the retina become damaged. This can cause vision loss or distortion when the abnormal vessels leak blood or fluid into the eye. About the Pagoda Study Pagoda ( NCT04108156 ) is a multicenter, randomized, active treatment-controlled, non-inferiority U.S.-based Phase III study evaluating the efficacy, safety and pharmacokinetics of Susvimo ® (ranibizumab injection) 100 mg/mL refilled every six months compared with monthly ranibizumab 0.5 mg intravitreal injections, in 634 people with diabetic macular edema. Participants were randomized 3:2 to receive either Susvimo refilled every six months or continued monthly intravitreal ranibizumab injections. In the Susvimo arm, participants received four loading doses of intravitreal ranibizumab before Susvimo implantation at week 16. The primary endpoint of the study is a change in best-corrected visual acuity score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline at the average of week 60 and week 64. Following primary analysis, participants who were initially randomized to intravitreal injections received Susvimo, with refills every 24 weeks. About the Pavilion Study Pavilion ( NCT04503551 ) is a multicenter, randomized, U.S.-based Phase III study evaluating the efficacy, safety and pharmacokinetics of Susvimo ® (ranibizumab injection) 100 mg/mL refilled every nine months compared with people under monthly clinical observation, in 174 people with diabetic retinopathy without center-involved diabetic macular edema. Participants were randomized 5:3 to receive either Susvimo with refills every nine months or monthly clinical observation, respectively. In the Susvimo arm, participants received two loading doses of intravitreal ranibizumab, before Susvimo implantation at week 4. The primary endpoint was the proportion of participants with at least a two-step improvement from baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale at week 52. Following the primary analysis, participants initially in the clinical observation arm received two ranibizumab loading doses before Susvimo implantation at week 64. About Susvimo ® (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant Susvimo ® (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant is a refillable implant surgically inserted into the eye during a one-time, outpatient procedure. Susvimo continuously delivers a customized formulation of ranibizumab over time. Susvimo is indicated for intravitreal use via the Susvimo eye implant only. Ranibizumab is a vascular endothelial growth factor (VEGF) inhibitor designed to bind to and inhibit VEGF-A, a protein that has been shown to play a critical role in the formation of new blood vessels and the leakiness of the vessels. Susvimo was previously called the Port Delivery System with ranibizumab in the U.S. The customized formulation of ranibizumab delivered by Susvimo is different from the ranibizumab intravitreal injection, a medicine marketed as Lucentis ® (ranibizumab injection), which is approved to treat wet, or neovascular, age-related macular degeneration (AMD) and other retinal diseases. Lucentis was first approved for wet AMD by the FDA in 2006. Susvimo U.S. Indications Susvimo (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD) who have previously responded to at least two intravitreal injections of a vascular endothelial growth factor inhibitor medication. Susvimo Important Safety Information WARNING: ENDOPHTHALMITIS The Susvimo implant has been associated with a 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. In clinical trials, 2.0% of patients receiving an implant experienced at least 1 episode of endophthalmitis. Warnings and Precautions: The Susvimo implant and the procedures associated with inserting, filling, refilling, and (if medically necessary) removing the implant can cause other serious side effects, including: An eye infection (endophthalmitis). Endophthalmitis is an infection of the eyeball that can cause permanent damage to your eye, including blindness. Endophthalmitis requires urgent (same-day) medical or surgical treatment. A missing layer on top of the white part of the eye (conjunctival erosion). Conjunctival erosion is an area that becomes missing (defect) in the layer (conjunctiva) that covers the white part of the eye, which may result in exposure of the implant. Conjunctival erosion may require surgical treatment. An opening of the layer that covers the white part of the eye (conjunctival retraction). Conjunctival retraction is an opening or gaping in the layer (conjunctiva) that covers the white part of the eye, which may cause the implant to be exposed. Conjunctival retraction may require surgical treatment. Tear and separation of layers of the retina (rhegmatogenous retinal detachment). Rhegmatogenous retinal detachment is a tear and separation of one of the layers of the retina in the back of the eye that senses light. Rhegmatogenous retinal detachment requires surgical treatment. Implant movement (implant dislocation): This movement may require surgical treatment to correct. Implant damage: Damage to the implant that prevents continued treatment (refills) with Susvimo. If the implant is not able to be properly refilled, a patient’s wet AMD may be inadequately treated and a physician may remove the implant and/or change the treatment. Bleeding (vitreous hemorrhage): Vitreous hemorrhage is bleeding within the gel-like substance (vitreous) inside of your eye. This may require an additional eye surgery. Bump on top of the white layer of the eye (conjunctival bleb): Conjunctival bleb is a small bulge in the layer (conjunctiva) that covers the white part of the eye where the implant is inserted. This may be due to leakage of fluid from the inside of the eye. This may require medical or surgical treatment. Temporary decrease in vision after the Susvimo procedure. Who should not receive Susvimo? Patients who have an infection in or around their eye, have active swelling around your eye that may include pain and redness, or have had an allergic reaction to ranibizumab or any of the ingredients in Susvimo in the past. Information for patients who are of childbearing potential If patients are pregnant, think that they might be pregnant, or plan to become pregnant: It is not known if Susvimo will harm an unborn baby. Patients should use birth control (contraception) during treatment with Susvimo and for 12 months after the last dose of Susvimo. Adverse Reactions The most common adverse reactions were blood on the white of the eye (72%), redness in the white of the eye (26%), sensitivity to light (23%), and eye pain (10%). These are not all the possible side effects of Susvimo. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. Please see additional Important Safety Information in the full Susvimo Prescribing Information , including BOXED WARNING or visit https://www.Susvimo.com . About Lucentis ® (ranibizumab injection) Lucentis ® is a vascular endothelial growth factor (VEGF) inhibitor designed to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels. Lucentis is FDA-approved for the treatment of patients with wet age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR) and myopic choroidal neovascularization (mCNV). Lucentis was developed by Genentech, a member of the Roche Group. The company retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world. Outside the United States, Lucentis is approved in more than 120 countries to treat adult patients with wet AMD, and for the treatment of visual impairment due to DME, due to macular edema secondary to both branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), and due to choroidal neovascularization (CNV). Lucentis Important Safety Information Lucentis is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab or any of the excipients in Lucentis. Hypersensitivity reactions may manifest as severe intraocular inflammation. Intravitreal injections, including those with Lucentis, have been associated with endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. Increases in intraocular pressure have been noted both pre-injection and post-injection with Lucentis. Although there was a low rate of arterial thromboembolic events (ATEs) observed in the Lucentis clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). Fatal events occurred more frequently in patients with DME and DR at baseline treated monthly with Lucentis compared with control. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded. Retinal vasculitis and/or retinal vascular occlusion have been reported. Patients should be instructed to report any change in vision without delay. In the Lucentis Phase III clinical trials, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, and increased intraocular pressure. The most common non-ocular side effects included nasopharyngitis, anemia, nausea, and cough. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. For additional safety information, please see Lucentis full Prescribing Information, available here: http://www.gene.com/download/pdf/lucentis_prescribing.pdf . About Genentech in Ophthalmology Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases, including rare and inherited conditions. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com . All trademarks used or mentioned in this release are protected by law.