Genentech Unveils Positive Phase II Results for the First-Ever Eye Implant to Achieve Sustained Delivery of a Biologic Medicine to Treat People With Wet Age-Related Macular Degeneration (AMD)

• Genentech’s investigational Port Delivery System with ranibizumab (PDS) is a small, refillable device, slightly longer than a grain of rice, surgically implanted in the eye and uniquely designed to continuously deliver a specialized formulation of the medicine, ranibizumab, over time
• People with wet AMD may need as often as monthly eye injections with the current standard of care
• The PDS is intended to reduce the burden of frequent eye injections by allowing people with wet AMD to go several months before needing a refill of the implant and address under-treatment that could lead to vision loss
• The majority of PDS patients went six months or longer between the implant of the device and the first required refill and patients in the high-dose PDS group achieved similar vision outcomes as monthly ranibizumab eye injections
• The PDS Phase III clinical development program is expected to begin later in 2018

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive, top line results from the Phase II LADDER study evaluating the efficacy and safety of its investigational Port Delivery System with ranibizumab (PDS) in people with wet age-related macular degeneration (AMD), a leading cause of blindness for people age 60 and over, in the United States.¹ The small, refillable eye implant, which is slightly longer than a grain of rice, is designed to allow people with wet AMD to go several months without needing to visit their ophthalmologist for treatment. The majority of PDS patients enrolled in the LADDER trial went six months or longer between implant of the device and the first, required refill. Vision outcomes in the high-dose PDS group were similar to monthly ranibizumab eye injections and were maintained throughout the study period. These data were presented by Carl C. Awh, M.D., of Tennessee Retina in Nashville, TN, at the 36^th Annual Meeting of the American Society of Retina Specialists (ASRS) in Vancouver, British Columbia, Canada.²

“If the PDS is successful, it could have a major impact on the way we treat people with wet AMD,” said Carl D. Regillo, M.D., FACS, Chief of Retina Service at Wills Eye Hospital in Philadelphia, PA and investigator for the LADDER study. “I believe that more consistent treatment could allow for better long-term vision outcomes in clinical practice.”

The current standard of care for wet AMD can be burdensome because it 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 and/or prevent vision loss. This high treatment burden with anti-VEGF therapy can lead to under-treatment of wet AMD and, potentially, less than optimal vision outcomes.^3,4

“LADDER is the first successful Phase II study of a long-acting delivery device for the treatment of wet AMD. We are highly encouraged by these results and the potential of the PDS, our first implantable, drug delivery program,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “With the PDS, we have an opportunity to make a positive impact by helping to potentially eliminate the burden of frequent treatments for people with wet AMD.”

LADDER study patients implanted with the PDS received one of three concentrations of ranibizumab: 10 mg/mL, 40 mg/mL or 100 mg/mL. For PDS patients receiving the 100 mg/mL dose (n=59), approximately 80 percent were able to go six months or longer until their first refill was required. Of the PDS patients receiving the 40 mg/mL (n=62) or the 10 mg/mL (n=58), 71.3 percent and 63.5 percent respectively, were able to go six months or longer before their first refill.

Secondary endpoints of the study included assessments of vision and anatomic outcomes when compared to monthly intravitreal ranibizumab 0.5 mg injections. Patients in the PDS 100 mg/mL arm achieved similar gains in Best Corrected Visual Acuity (BCVA) and similar reductions in central retina thickness compared to patients receiving monthly ranibizumab 0.5 mg injections.

The PDS is implanted during a surgical procedure. It is refilled using a customized needle in a minimally invasive office-based procedure. The results from this study will help determine the most appropriate dose and fixed treatment interval to study in the Phase III program to sustain optimal vision outcomes in clinical practice for patients with wet AMD.

Additional data analyses of the LADDER study are on-going and will be presented at future medical meetings. The PDS Phase III clinical development program is expected to begin later in 2018.

About Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a disease that impacts 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 Wet AMD is an advanced form of the disease that can cause rapid and severe vision loss.⁵ Approximately 11 million people in the United States have some form of AMD and of those about 1.1 million have wet AMD.⁵

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 the LADDER Study

LADDER (Long Acting DElivery of Ranibizumab; NCT02510794)⁶ is a Phase II study designed to evaluate the efficacy and safety of the Port Delivery System with ranibizumab (PDS) in people with wet age-related macular degeneration (AMD) who have previously responded to treatment with anti-vascular endothelial growth factor (VEGF) therapies. This multicenter, randomized, interventional, active treatment-controlled study enrolled 243 participants in approximately 50 sites across the United States. The primary objective of LADDER was to determine the time until a patient first required a refill of the implant, assessing the efficacy and safety of three different concentrations of ranibizumab compared to monthly intravitreal injections of ranibizumab 0.5 mg.

The PDS contains a special 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) and FDA-approved to treat wet AMD and other retinal diseases.

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 [phone].

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 the 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 National Health Institute Medline Plus. Leading Causes of Blindness. Available at: https://medlineplus.gov/magazine/issues/summer08/articles/summer08pg14-15.html. Accessed May 2018.
² LADDER Trial of the Port Delivery System for Ranibizumab: Preliminary Study Results. Presented by Awh, C on July 25, 2018 during the Late Breaking Abstract session at the 36^th Annual Meeting of the American Society of Retina Specialists (ASRS) in Vancouver, British Columbia, Canada.
³ Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. British Journal of Ophthalmology. 2015;99:220-226.
⁴ Rao P, Lum F, 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: 522-528
⁵ BrightFocus Foundation. Macular Degeneration: Essential Facts. Available at: http://www.brightfocus.org/macular/news/macular-essential-facts. Accessed May 2018.
⁶ Study of the Efficacy and Safety of the Ranibizumab Port Delivery System (RPDS) for Sustained Delivery of Ranibizumab in Participants With Subfoveal Neovascular Age-Related Macular Degeneration (AMD) (LADDER). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/study/NCT02510794. Accessed May 2018.