New Two-Year Data for Genentech’s Vabysmo and Susvimo Reinforce Potential to Maintain Vision With Fewer Treatments for People With Two Leading Causes of Vision Loss

‒ In the YOSEMITE and RHINE studies in diabetic macular edema, at least 60% of eligible Vabysmo patients could extend treatment to every four months at two years, compared to 50% at year one –

‒ Almost 80% of eligible Vabysmo patients could extend treatment to every three months or longer in both studies –

‒ In the Archway study in wet age-related macular degeneration, 95% of Susvimo patients maintained a six-month treatment schedule at two years –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that new two-year data from its Phase III studies of Vabysmo™ (faricimab-svoa) and Susvimo™ (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant will be presented at Angiogenesis, Exudation and Degeneration 2022 on Feb. 12. These longer-term results from the Vabysmo YOSEMITE and RHINE studies in diabetic macular edema (DME) and the Susvimo Archway study in wet, or neovascular, age-related macular degeneration (AMD) further reinforce the potential to allow for longer time between treatments and fewer eye injections for people with these conditions, while still achieving and maintaining vision gains seen with previous standard-of-care injections. Wet AMD and DME are two leading causes of vision loss, together affecting nearly 2 million people in the U.S., which require treatment with eye injections as often as once a month.

“Results from these three studies reinforce the potential of Vabysmo and Susvimo to redefine standards of care and reduce treatment burden for people living with diabetic macular edema and wet AMD,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “These two first-of-their-kind treatments are the culmination of over a decade of pioneering research, aiming to better address the needs of people with retinal conditions.”

In the YOSEMITE and RHINE studies, at least 60% of people eligible for extended dosing with Vabysmo could be treated every four months at two years – a 10 percentage point increase since the primary analysis at one year – while achieving non-inferior vision gains versus aflibercept given every two months. Furthermore, nearly 80% of people eligible for extended dosing with Vabysmo could be treated every three months or longer. In the Archway study, Susvimo allowed 95% of people to go six months between treatments at two years – the fourth complete refill-exchange interval – while maintaining vision outcomes that were non-inferior to monthly ranibizumab injections. Across all three studies, with longer follow-up, Vabysmo and Susvimo continued to be generally well tolerated, with favorable benefit-risk profiles. Safety will continue to be monitored closely in the post-market setting.

Vabysmo is the first bispecific antibody for the eye approved by the U.S. Food and Drug Administration (FDA) and the only injectable eye medicine approved for treatments from one to four months apart in the first year following four initial monthly loading doses, based on evaluation of the patient’s anatomy and vision outcomes. Vabysmo is designed to block two disease pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A are thought to contribute to vision loss by destabilizing blood vessels, which may cause new leaky blood vessels to form and increase inflammation. While additional research continues, inhibition of both pathways has been shown in preclinical studies to have potentially complementary benefits, stabilizing vessels and thereby reducing vessel leakage and inflammation more than inhibition of VEGF-A alone.

Susvimo is the first wet AMD treatment in 15 years to provide an alternative to standard-of-care eye injections. By continuously delivering medicine into the eye through a refillable implant, Susvimo is the only FDA-approved treatment that may help people with wet AMD maintain their vision with as few as two treatments per year.

Vabysmo: YOSEMITE and RHINE Two-Year Results

In the YOSEMITE and RHINE studies, DME patients received Vabysmo, given either every two months or up to every four months using a treat-and-extend approach, or aflibercept given every two months. Two-year results showed Vabysmo patients maintained the vision improvements achieved in the first year and vision gains continued to be non-inferior to those achieved by aflibercept patients. In YOSEMITE, the average vision gains from baseline at two years were +10.7 eye chart letters in both the Vabysmo treat-and-extend and two-month arms, and +11.4 letters in the aflibercept arm. In RHINE, the average vision gains from baseline at two years were +10.1 and +10.9 letters in the Vabysmo treat-and-extend and two-month arms, respectively, and +9.4 letters in the aflibercept arm.

Importantly, 60% (n=162/270) of Vabysmo treat-and-extend patients in YOSEMITE and 64.5% (n=185/287) in RHINE achieved four-month dosing at two years. This is an increase over one-year results, which showed 52.8% (n=151/286) of Vabysmo treat-and-extend patients in YOSEMITE and 51% (n=157/308) in RHINE achieved four-month dosing. An additional 18.1% (n=49/270) of Vabysmo treat-and-extend patients in YOSEMITE and 13.6% (n=39/287) in RHINE achieved three-month dosing. Combined, almost 80% of Vabysmo treat-and-extend patients were able to go three months or longer between treatments at the end of the second year. Across study arms, Vabysmo showed consistent two-step or better improvement in diabetic retinopathy according to the Early Treatment Diabetic Retinopathy Study – Diabetic Retinopathy Severity Score (ETDRS-DRSS). At two years, 42.8% of Vabysmo treat-and-extend patients in YOSEMITE and 44.3% in RHINE achieved a two-step or better improvement from baseline. In the two-month Vabysmo arms, 51.4% and 53.5% of patients in YOSEMITE and RHINE, respectively, achieved a two-step or better improvement in diabetic retinopathy severity. Vabysmo given at intervals of up to four months continued to demonstrate greater reductions in central subfield thickness (CST) compared to aflibercept given every two months in both studies. Safety results were consistent across study arms, with no cases of retinal vasculitis or retinal occlusive events.

One-year results from the YOSEMITE and RHINE studies and the TENAYA and LUCERNE studies in wet AMD were recently published in The Lancet.

Susvimo: Archway Two-Year Results

Wet AMD patients in Archway received either Susvimo refilled every six months or monthly ranibizumab 0.5 mg eye injections. Two-year results showed vision was maintained by Susvimo patients and continued to be non-inferior to that achieved with monthly ranibizumab injections. Susvimo patients averaged -1.1 eye chart letters in visual acuity from baseline at two years, while monthly ranibizumab patients averaged -0.5 letters from baseline. In addition, 95% of Susvimo patients were able to go six months without needing additional treatment in the second, third and fourth refill-exchange intervals. In Archway, Susvimo was generally well tolerated, with a favorable benefit-risk profile. The most common adverse events of special interest (≥5%) were cataract, conjunctival bleb and vitreous hemorrhage. The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely.

In addition to Archway results, two-year interim data from the ongoing Phase III Portal study will be presented at the Angiogenesis meeting. Portal is an extension study evaluating the long-term safety and efficacy of Susvimo in wet AMD.

Vabysmo is approved by the FDA for the treatment of wet AMD and DME. Susvimo is approved by the FDA for the treatment of people with wet AMD who have previously responded to at least two anti-VEGF injections. Vabysmo is currently under review by the European Medicines Agency for the treatment of wet AMD and DME and Susvimo is under review for the treatment of wet AMD. Submissions to other regulatory authorities around the world are ongoing.

Genentech has a robust Phase III clinical development program for Vabysmo and Susvimo. For Vabysmo, the program includes AVONELLE-X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and tolerability of Vabysmo in wet AMD, and RHONE-X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and tolerability of Vabysmo in DME. Additionally, the COMINO and BALATON trials are also underway, evaluating the efficacy and safety of Vabysmo in people with macular edema following retinal vein occlusion.

For Susvimo, the clinical development program includes the Portal, Pagoda, Pavilion and Velodrome studies. Portal is an extension study evaluating the long-term safety and efficacy of Susvimo in wet AMD. Pagoda is evaluating Susvimo for the treatment of DME, while Pavilion is a study of Susvimo in diabetic retinopathy without DME. Velodrome is evaluating Susvimo refilled every nine months in wet AMD.

About the YOSEMITE and RHINE Studies

YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomized, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of Vabysmo™ (faricimab-svoa) compared to aflibercept in 1,891 people with diabetic macular edema (940 in YOSEMITE and 951 in RHINE). The studies each have three treatment arms: Vabysmo 6.0 mg administered up to every four months after four initial monthly doses using a treat-and-extend approach; Vabysmo 6.0 mg administered at two-month intervals after six initial monthly doses; and aflibercept administered at fixed two-month intervals after five initial monthly doses. Dosing schedule for patients within the treat-and-extend arm was determined by central subfield thickness (CST) and visual acuity. In all three arms, sham injections were administered at study visits when treatment injections were not scheduled to maintain the masking of investigators and participants.

The primary endpoint of the studies is the average change in best-corrected visual acuity (BCVA) 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 one year, averaged over weeks 48, 52 and 56. Secondary endpoints include: safety; the percentage of participants in the treat-and-extend arm receiving Vabysmo every one, two, three and four months, at week 52; the percentage of participants achieving a two-step or greater improvement from baseline in diabetic retinopathy severity at week 52; the percentage of participants achieving a gain, and the percentage avoiding a loss, of 15 letters or more in BCVA from baseline over time; change in CST from baseline over time; and percentage of patients with absence of intraretinal fluid over time.

About the Archway Study

Archway (NCT03677934) was a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of Susvimo™ (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant administered via the Susvimo eye implant, refilled every six months at fixed intervals, compared to monthly intravitreal injections of ranibizumab 0.5 mg in 415 people living with wet, or neovascular, age-related macular degeneration. Patients enrolled in Archway were responders to prior treatment with anti-vascular endothelial growth factor (VEGF) therapy. In both study arms, patients were treated with at least three anti-VEGF injections within the six months prior to their Archway screening visit. The primary endpoint of the study was the change in best-corrected visual acuity (BCVA) score from baseline at the average of Week 36 and Week 40. Secondary endpoints include safety, overall change in vision (BCVA) from baseline and change from baseline in center point thickness over time.

About Diabetic Macular Edema

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 Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a condition that affects the macula, the part of the eye that provides sharp, central vision needed for activities like reading, and is a leading cause of blindness for people aged 60 and over in the U.S. Wet, or neovascular, AMD is an advanced form of the disease that can cause rapid and severe vision loss. Approximately 11 million people in the U.S. have some form of AMD, and of those, about 1.1 million have wet AMD.

Wet AMD is caused by growth of abnormal blood vessels, also referred to as choroidal neovascularization (CNV), into the macula. These vessels leak fluid and blood and cause scar tissue that destroys the central retina. This process results in a deterioration of sight over a period of months to years.

About Vabysmo™ (faricimab-svoa)

Vabysmo (faricimab-svoa) is the first bispecific antibody approved for the eye. It targets and inhibits two disease pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A contribute to vision loss by destabilizing blood vessels, causing new leaky blood vessels to form and increasing inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilize blood vessels.

Vabysmo U.S. Indications

Vabysmo (faricimab-svoa) is a prescription medicine given by injection into the eye, used to treat adults with neovascular (wet) age‑related macular degeneration (AMD) and diabetic macular edema (DME).

Important Safety Information

Contraindications

Vabysmo is contraindicated in patients who have an infection in or around their eye, have active swelling around their eye that may include pain and redness, or are allergic to Vabysmo or any of the ingredients in Vabysmo.

Warnings and Precautions

• Injections like the one for Vabysmo can cause an eye infection (endophthalmitis) or separation of layers of the retina (retinal detachment). Patients should seek medical care if they experience increasing eye pain, vision loss, sensitivity to light, or redness in the white of the eye.
• Vabysmo may cause a temporary increase in pressure in the eye (intraocular pressure), which occurs 60 minutes after the injection.
• Although not common, Vabysmo patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes (thromboembolic events). In clinical studies for wet AMD during the first year, 7 out of 664 patients treated with Vabysmo reported such an event. In DME studies during the first year, 25 out of 1,262 patients treated with Vabysmo reported such an event.

Adverse Reactions

The most common adverse reaction (≥5%) reported in patients receiving Vabysmo was blood on the white of the eye (conjunctival hemorrhage, 7%). These are not all the possible side effects of Vabysmo.

Pregnancy, Lactation, Females and Males of Reproductive Potential

• Based on how Vabysmo interacts with your body, there may be a potential risk to an unborn baby. Patients should use birth control before their first injection, during their treatment with Vabysmo, and for 3 months after their last dose of Vabysmo.
• It is not known if Vabysmo passes into breast milk. Patients should talk to their healthcare provider about the best way to feed their baby if they receive Vabysmo.

Patients may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information in the full Vabysmo Prescribing Information.

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 is different from the ranibizumab intravitreal injection, a medicine marketed as Lucentis^® (ranibizumab injection), which is FDA-approved to treat wet age-related macular degeneration (AMD) and other retinal diseases.

Susvimo Indication

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 three-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. In clinical trials, 2.0% of patients receiving an implant experienced at least one 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.
• 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 inflammation in their eye, or have had an allergic reaction to ranibizumab or any of its 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 refill of Susvimo.
• If patients are breastfeeding or plan to breastfeed. Susvimo is not recommended during breastfeeding. It is not known if Susvimo passes into breast milk.

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.

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

Patients should not use Lucentis if they have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.

Lucentis is a prescription medication given by injection into the eye, and it has side effects. Some Lucentis patients have had detached retinas and serious infections inside the eye. If your eye becomes red, sensitive to light, or painful, or if there is a change in vision, call or visit your eye doctor right away.

Some patients have had increased eye pressure before and within 1 hour of an injection.

Uncommonly, Lucentis patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes.

Fatal events were seen more often in patients with DME and DR with Lucentis compared with patients who did not receive Lucentis. Although there were only few fatal events which included causes of death typical of patients with advanced diabetic complications, these events may be caused by Lucentis.

Some Lucentis patients have serious side effects related to the injection. These include serious infections inside the eye, detached retinas, and cataracts. The most common eye-related side effects are increased redness in the white of the eye, eye pain, small specks in vision, and increased eye pressure. The most common non–eye related side effects are nose and throat infections, anemia, nausea and cough.

Patients may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see Lucentis full Prescribing Information,

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