Phase III Data Show Port Delivery System With Ranibizumab Enabled Over 98% of Patients to Go Six Months Between Treatments for Neovascular Age-Related Macular Degeneration

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) today announced detailed results from the Phase III Archway study evaluating its investigational Port Delivery System with ranibizumab (PDS) for the treatment of neovascular or “wet” age-related macular degeneration (nAMD), a leading cause of blindness in the U.S.1 In Archway, 98.4% of PDS patients were able to go six months without needing additional treatment and achieved vision outcomes equivalent to patients receiving monthly ranibizumab eye injections, a current standard of care.2 In the study, PDS was generally well-tolerated, with a favorable benefit-risk profile.2 PDS is a permanent refillable eye implant, approximately the size of a grain of rice, which continuously delivers a customized formulation of ranibizumab over a period of months. PDS is the first nAMD therapy to achieve positive Phase III results for this extended length of time between treatments.3 These new data will be discussed virtually during the 38th Annual Meeting of the American Society of Retina Specialists (ASRS) on Sunday, July 26, 2020. A recorded presentation of these data is now available to ASRS attendees through the meeting web portal.

“Based on the Archway results, PDS could potentially reduce the number of treatments from as many as 12 per year to two per year for neovascular AMD patients, without sacrificing efficacy,” said Carl Regillo, M.D., Chief of Retina Service at Wills Eye Hospital in Philadelphia and an Archway study investigator. “While effective therapies exist for this condition, I know from clinical experience that it can be difficult for patients and caregivers to commit to frequent treatments, and patients who are not treated frequently enough may be at risk of losing vision.”

The current standard of care for nAMD requires patients to visit their ophthalmologist as often as monthly for eye injections of anti-vascular endothelial growth factor (VEGF) therapy to help maintain vision gains or prevent vision loss.4 This high treatment burden with anti-VEGF therapy can lead to under-treatment of nAMD and, potentially, less than optimal vision outcomes.4,5

“For over a decade, we have been working to develop new treatments that better address the unmet needs of people living with neovascular AMD,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Based on these data, we believe that the continuous delivery mechanism enabled by PDS may offer effective, reliable results while also alleviating the treatment burden. We are excited to share the data with regulatory authorities with the aim of bringing this new treatment option to patients as soon as possible.”

Patients in Archway received either PDS refilled every six months with a customized formulation of ranibizumab or monthly ranibizumab 0.5 mg eye injections. Patients in the study had received prior treatment with anti-VEGF therapy and were confirmed anti-VEGF responders. The primary endpoint of the study measured the change from baseline in best-corrected visual acuity (BCVA) averaged over Week 36 and Week 40. In the PDS arm, patients gained an average of 0.2 eye chart letters in visual acuity from baseline, with 98.4% (n=244/248) of patients maintaining the fixed six-month refill schedule within the first refill period. Patients treated monthly with ranibizumab injections gained an average of 0.5 letters in visual acuity from baseline. According to pre-specified study criteria, PDS was shown to be non-inferior and equivalent to monthly ranibizumab injections. In addition, PDS controlled retinal thickness as effectively as monthly ranibizumab, with patients in both arms achieving a mean change in center point thickness within 10 µm from baseline. Safety data from the study support a favorable benefit-risk profile for PDS. The PDS implant insertion surgery and refill-exchange procedures were generally well-tolerated by patients and the systemic safety of PDS was comparable to monthly ranibizumab injections.2

In addition to Archway, the Portal long-term extension study is investigating the long-term safety and tolerability of PDS for the treatment of nAMD.6 PDS is also being studied in the Phase III Pagoda trial for the treatment of diabetic macular edema, a vision-threatening complication of diabetes.7 The Pagoda trial is actively recruiting patients.

Results from the Archway study will be submitted to health authorities around the world, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), for consideration of regulatory approval for the treatment of nAMD.

About the Archway Study8

Archway (NCT03677934) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of Port Delivery System with ranibizumab (PDS), refilled every six months at fixed intervals, compared to monthly intravitreal injections of ranibizumab 0.5 mg in 418 people living with neovascular age-related macular degeneration (nAMD). 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 is the 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 the average of week 36 and week 40. Secondary endpoints include safety; overall change in BCVA from baseline; and change from baseline in center point thickness over time.

About Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a condition that affects the part of the eye that provides sharp, central vision needed for activities like reading and is a leading cause of blindness for people age 60 and over in the U.S.1 Neovascular or “wet” AMD (nAMD) is an advanced form of the disease that can cause rapid and severe vision loss.9 Approximately 11 million people in the United States have some form of AMD and of those about 1.1 million have nAMD.9

Neovascular 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 Port Delivery System with ranibizumab (PDS)

Port Delivery System with ranibizumab (PDS) is a permanent refillable eye implant, approximately the size of a grain of rice, which is designed to continuously release a customized formulation of ranibizumab into the eye over time. Ranibizumab 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 and the leakiness of the vessels.10

PDS contains a customized formulation of ranibizumab not approved by the U.S. Food and Drug Administration (FDA). It is different from the ranibizumab intravitreal injection, a medicine marketed as Lucentis® (ranibizumab injection) which is FDA-approved to treat neovascular age-related macular degeneration (nAMD) and other retinal diseases.

By maintaining therapeutic drug concentration levels of ranibizumab with two refills per year, PDS may offer greater outcomes certainty in terms of vision gains and maintaining those gains for people living with nAMD. Additionally, by decreasing the need for frequent injections and physician visits, PDS may reduce the burden of treatment associated with standard anti-VEGF treatments.4 The Archway trial of PDS in nAMD is evaluating a regimen of PDS implantation followed by twice-yearly refills.

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 U.S. and Novartis has exclusive commercial rights for the rest of the world.

Outside the U.S., Lucentis is approved in more than 120 countries to treat adult patients with wet AMD, for the treatment of visual impairment due to DME, due to macular edema secondary to both branch retinal vein occlusion (BRVO), 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, 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. The company is also investigating platforms for sustained ocular drug delivery, including Port Delivery System with ranibizumab (PDS).

Genentech’s parent company, Roche, is investigating a bispecific antibody for the treatment of retinal eye diseases.

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.

1 Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures. Accessed June 2020.
2 Campochiaro, P, et al. Primary Analysis Results of the Phase 3 Archway Trial of the Port Delivery System With Ranibizumab for Patients With Neovascular AMD. American Society of Retina Specialists Annual Meeting; 2020 Jul 24-26.
3 Genentech Data on File.
4 Holz FG, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. The British Journal of Ophthalmology. 2015;99:220-6.
5 Rao P, et al. Real-World Vision in Age-Related Macular Degeneration Patients Treated with Single Anti–VEGF Drug Type for 1 Year in the IRIS Registry. Ophthalmology. 2018;125:522-28.
6 ClinicalTrials.gov. Extension Study for the Port Delivery System With Ranibizumab (Portal). Available from: https://clinicaltrials.gov/ct2/show/NCT03683251. Accessed June 2020.
7 ClinicalTrials.gov. This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab (Pagoda). Available from: https://clinicaltrials.gov/ct2/show/NCT04108156. Accessed June 2020.
8 ClinicalTrials.gov. A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (Archway) [Internet; cited 2020 June 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT03677934. Accessed June 2020.
9 BrightFocus Foundation. Macular Degeneration: Essential Facts. Available at: http://www.brightfocus.org/macular/news/macular-essential-facts. Accessed June 2020.
10 Wykoff, CC, et al. Optimizing anti-VEGF treatment outcomes for patients with neovascular age-related macular degeneration. Journal of Managed Care & Specialty Pharmacy, 2018; 24(2-a Suppl):S3-S15.

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