Saturday, Oct 27, 2018
South San Francisco, CA -- October 27, 2018 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive results from the Phase II STAIRWAY study which explored the extended durability of faricimab (RG7716) in the treatment of wet age-related macular degeneration (AMD), a leading cause of blindness in people aged 60 and over in the United States.3 At 52 weeks, faricimab patients dosed either every 16 weeks or every 12 weeks demonstrated sustained vision outcomes comparable to ranibizumab dosed every four weeks. Results of the study were presented as a late-breaking oral presentation during the 2018 American Academy of Ophthalmology’s (AAO) 122nd Annual Meeting in Chicago, Illinois.1
“Because current anti-VEGF monotherapies for wet AMD are burdensome, requiring frequent clinic visits for eye injections, some people are under-treated and experience subsequent declining vision over time,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The STAIRWAY data show the potential of faricimab to allow fewer injections while achieving and sustaining the same visual gains seen with a current standard of care. Based on these data, we will be initiating a global Phase III program for faricimab in wet AMD.”
STAIRWAY is a 52-week study that assessed two extended dosing regimens of faricimab 6.0 mg given every 16 weeks or every 12 weeks, compared to ranibizumab 0.5 mg every four weeks. At week 24 (three months after the last of four loading doses), patients randomized to faricimab every 16 weeks were switched to 12-week dosing if they were shown to have active disease, per pre-defined criteria. At week 24, 65 percent (n=36/55) of people treated with faricimab had no active disease, highlighting the potential of 16-week dosing in nearly two-thirds of patients. Initial vision gains, as measured by Best Corrected Visual Acuity (BCVA), were fully maintained through to week 52 with 16- and 12-week dosing regimens. People treated with faricimab dosed every 16 weeks experienced a mean improvement of 11.4 chart letters from baseline, compared to 10.1 letters in patients treated with faricimab dosed every 12 weeks and 9.6 letters in patients treated with ranibizumab 0.5 mg dosed every four weeks. The three treatment regimens were similar in both the proportion of patients gaining more than 15 letters and avoiding a loss of more than 15 letters. Comparable reductions in central retina thickness were also observed in people treated with both dosing intervals of faricimab and those treated with ranibizumab.1 In STAIRWAY, the rates of ocular and systemic adverse events observed with faricimab were similar to the rates observed with ranibizumab. No new safety signals were observed. The overall safety profile of faricimab appears consistent with the safety profile reported in patients with wet AMD who receive intravitreal anti-VEGF therapies.1
In addition, data on the investigational Port Delivery System with ranibizumab (PDS) in patients with wet AMD were also presented at the AAO Annual Meeting, comprising further data from the Phase II Ladder study, and the trial design of the Phase III Archway study.2 The small, refillable eye implant, which is slightly longer than a grain of rice, is designed to allow most people with wet AMD to go six months without needing a refill.
Top line results presented earlier this year showed the majority of PDS patients – including approximately 80 percent of patients in the high-dose PDS group – went six months or longer between the implantation and the first required refill of the device. Importantly, patients in the high-dose PDS group achieved similar visual outcomes as ranibizumab 0.5 mg dosed every four weeks.4 Based on the data of the Phase II Ladder program, the pivotal Phase III Archway clinical trial and the Portal label extension study were initiated in September 2018. These studies will evaluate the efficacy and safety of the PDS 100 mg/mL concentration in patients with wet AMD at a fixed dosing interval of 24 weeks.5, 6
Faricimab and the PDS are the two most advanced investigational treatments in Genentech and Roche’s robust ophthalmology pipeline. In addition to Archway, two pivotal Phase III studies for faricimab are currently open and enrolling: RHINE (NCT03622593) and YOSEMITE (NCT03622580). These two studies are designed to investigate the efficacy and safety of faricimab compared with aflibercept in people with diabetic macular edema (DME).7, 8 Based on STAIRWAY, a global Phase III program for faricimab in wet AMD is anticipated to commence in 2019.
Follow Genentech on Twitter via @genentech and keep up to date with AAO 2018 Congress news and updates by using the hashtag #AAO2018.
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.3 Wet AMD 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 wet AMD.9
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.
Current standards of care for wet AMD target vascular endothelial growth factor (VEGF) alone, which effectively addresses blood vessel leakage, but only partially addresses the inflammation associated with the condition. In addition, people receiving anti-VEGF therapy may need as often as monthly eye injections. This high treatment burden can lead to under-treatment of wet AMD and, potentially, less than optimal vision outcomes.10, 11 There is a significant unmet need for efficacious, longer-lasting therapies for people with this condition.
About STAIRWAY and faricimab
Faricimab is the first bispecific antibody designed specifically for intravitreal use to simultaneously bind to and neutralize both Angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) with high potency and specificity. In wet age-related macular degeneration (AMD), Ang-2 works synergistically with VEGF to drive pathologic blood vessel permeability and destabilization, abnormal blood vessel growth and fluid leakage, which contribute to vision loss. Ang-2 also plays an important role in multiple aspects of inflammation in wet AMD.12, 13
STAIRWAY (NCT03038880) is a Phase II, multicenter, randomized, comparator-controlled, parallel group clinical trial, investigating the efficacy, safety and pharmacokinetics of faricimab administered with extended dosing regimens in 76 treatment-naïve people with wet AMD.1
About Ladder, Archway and the Investigational Port Delivery System with ranibizumab (PDS)
The investigational Port Delivery System with ranibizumab (PDS) is a small, refillable device, slightly longer than a grain of rice, surgically implanted in the eye during a procedure performed under local anesthesia. The PDS is uniquely designed to continuously deliver a specialized formulation of ranibizumab over time. 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.
Ladder (NCT02510794) is a Phase II, multicenter, randomized, interventional, active treatment-controlled study designed to evaluate the efficacy and safety of the PDS in people with wet age-related macular degeneration (AMD) who have previously responded to treatment with anti-vascular endothelial growth factor (VEGF) therapies.4 Additional data analyses of the Ladder study are ongoing and will be presented at future medical meetings.
Archway (NCT03677934) will evaluate the efficacy and safety of the PDS 100 mg/mL in patients with wet AMD with a fixed dosing interval of 24 weeks.5 In the trial, patients will be randomized into one of two arms: Arm A will receive the PDS 100 mg/mL and refills at fixed 24-week intervals and Arm B will receive monthly intravitreal injections of ranibizumab 0.5 mg. The primary endpoint of Archway is the change from baseline in Best Corrected Visual Acuity (BCVA) at weeks 36 and 40.
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 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 Khanani AM, et al. Simultaneous Inhibition of VEGF and Ang-2 with Faricimab in Neovascular AMD: STAIRWAY Phase 2 Results. Presented at the 2018 American Academy of Ophthalmology (AAO) Annual Meeting; 2018 Oct 26; Chicago, United States.
2 Pieramici D, et al. Port Delivery System With Ranibizumab (PDS): From Dose Ranging in Ladder Phase 2 to Archway Phase 3 Study Design. Presented at the 2018 American Academy of Ophthalmology (AAO) Annual Meeting; 2018 Oct 27; Chicago, United States.
3 National Health Institute Medline Plus. Leading Causes of Blindness. Available at: https://medlineplus.gov/magazine/issues/summer08/articles/summer08pg14-15.html. Accessed October 2018.
4 Awh C, et al. Ladder trial of the Port Delivery System for ranibizumab: Initial study results. Presented at the 36th Annual Meeting of the American Society of Retina Specialists (ASRS); 2018 Jul 20-25; Vancouver, British Columbia, Canada.
5 ClinicalTrials.gov. A Phase III Study to Evaluate the Port Delivery System Implant With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (Archway). Available from: https://clinicaltrials.gov/ct2/show/study/NCT03677934. Accessed October 2018.
6 ClinicalTrials.gov. Extension Study for the Port Delivery System With Ranibizumab (Portal). Available from: https://clinicaltrials.gov/ct2/show/NCT03683251. Accessed October 2018.
7 ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants With Diabetic Macular Edema (RHINE). Available from: https://clinicaltrials.gov/ct2/show/NCT03622593. Accessed October 2018.
8 ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants With Diabetic Macular Edema (YOSEMITE). Available from: https://clinicaltrials.gov/ct2/show/NCT03622580. Accessed October 2018.
9 BrightFocus Foundation. Macular Degeneration: Essential Facts. Available at: http://www.brightfocus.org/macular/news/macular-essential-facts. Accessed October 2018.
10 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.
11 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.
12 Chakravarthy U BC, Brown D, Campochiaro P, et al. Phase 1 trial of anti–vascular endothelial growth factor/antiangiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration. Ophthalmology Retina. 2017; 1: 474-485.
13 Rangasamy S, Srinivasan R, Maestas J, et al. A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011; 52:3784-3791.