New York — Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from two Phase III studies of Lucentis® (ranibizumab injection) in macular edema due to retinal vein occlusion (RVO), which showed, on average, patients given either of two doses of Lucentis had a clinically and statistically significant improvement in vision as measured by the primary endpoint of mean change from baseline in best-corrected visual acuity (BCVA) at six months compared to patients receiving sham injections. Results from both trials were presented today at the Retina Congress 2009 meeting.
Data from the BRAVO study in branch-RVO showed at month six, patients who received 0.3 mg of Lucentis had a mean gain from baseline BCVA of 16.6 letters and patients who received 0.5 mg of Lucentis had a mean gain of 18.3 letters (compared to 7.3 letters in patients receiving sham injections). In the CRUISE study in central-RVO, at month six, patients who received 0.3 mg of Lucentis had a mean gain from baseline BCVA of 12.7 letters and patients who received 0.5 mg of Lucentis had a mean gain of 14.9 letters (compared to 0.8 letters for patients receiving sham injections). In both trials, a statistically significant mean gain in BCVA was observed as early as day seven for both doses of Lucentis compared with sham. The studies were not designed to compare the two doses of Lucentis.
“RVO can lead to sudden loss of vision for which there are few treatment options,” said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. “As early as seven days after their first injection, patients who received monthly injections of Lucentis had, on average, a statistically significant improvement in their vision that lasted through six months.”
BRAVO is a multicenter, randomized, double-masked, sham injection-controlled Phase III study of 397 patients designed to assess the safety and efficacy profile of Lucentis in macular edema secondary to branch-RVO. Results at six months include:
- 55.2 percent (74/134) of patients who received 0.3 mg of Lucentis and 61.1 percent (80/131) who received 0.5 mg of Lucentis had their vision improved by 15 letters or more on the study eye chart (compared to 28.8 percent (38/132) of patients receiving sham injections).
- Mean gain in BCVA was observed beginning at day seven with a 7.6 and 7.4 letter gain in the 0.3 mg and 0.5 mg study arms of Lucentis, respectively (compared with 1.9 letters in the sham injection arm).
CRUISE is a multicenter, randomized, double-masked, sham injection-controlled Phase III study designed to assess the safety and efficacy profile of Lucentis. The study includes 392 patients with macular edema secondary to central-RVO and at six months showed:
- 46.2 percent (61/132) of patients given 0.3 mg of Lucentis and 47.7 percent (62/130) given 0.5 mg of Lucentis had their vision improved by 15 letters or more (compared to 16.9 percent (22/130) of patients receiving sham injections).
- Mean gain in BCVA was observed beginning at day seven with an 8.8 and 9.3 letter gain in the 0.3 mg and 0.5 mg study arms of Lucentis, respectively (compared with 1.1 letters in the sham injection arm).
An analysis of the six-month data from both studies showed a safety profile consistent with previous Lucentis Phase III trials in wet (neovascular) age-related macular degeneration (AMD). Common ocular adverse events in both studies that occurred more frequently in the Lucentis arms than in the control group included conjunctival hemorrhage, retinal exudates, and eye pain. Serious ocular adverse events were uncommon and in the BRAVO study included one case of retinal detachment/tear in the 0.3 mg dose group and one case of endophthalmitis in the 0.5 mg dose group. In the CRUISE study serious ocular adverse events were uncommon with one case of vitreous hemorrhage in the sham injection group. No cases of endophthalmitis were reported in any of the treatment arms during the six-month treatment period in CRUISE. Among non-ocular serious adverse events in the BRAVO study, one cerebrovascular accident occurred in the sham injection group and two events occurred in the 0.5 mg dose group: one cerebrovascular accident that resulted in death and one myocardial infarction. In CRUISE, non-ocular serious adverse events were uncommon and included one case of either myocardial infarction or acute coronary syndrome in each of the three groups. No cerebrovascular accidents or deaths occurred during the six-month treatment period in CRUISE.
About the Studies
Both BRAVO and CRUISE are 12-month studies consisting of a six-month, sham-controlled treatment period, followed by a six-month observation period (during which all participants are eligible to receive Lucentis as needed). During the first six-month period, participants in both trials received monthly injections of either 0.3 mg or 0.5 mg of Lucentis (n=265) or monthly sham injections (n=132). In the BRAVO study, all participants who met pre-specified criteria were eligible to receive rescue laser treatment during the first six-month period. The primary endpoint for both trials is the mean change from baseline in best-corrected visual acuity score at six months compared to sham.
RVO occurs when blood flow through a retinal vein becomes blocked, causing swelling (macular edema) and hemorrhages in the retina, which may result in vision loss. Sudden blurring or vision loss in all or part of one eye is common with RVO. RVO can affect people across a wide range of ages, from young, working-aged adults to the elderly.
There are two main types of RVO: branch-RVO, which affects an estimated 868,000 people, and central-RVO, which affects an estimated 259,000 people in the United Statesi. Branch-RVO occurs when one of the branches of the main vein of the eye becomes blocked. Central-RVO occurs when the main vein of the eye, located at the optic nerve, becomes blocked.
Lucentis is a vascular endothelial growth factor (VEGF) inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of neovascular (wet) AMD at a dose of 0.5 mg monthly by intravitreal injection. Lucentis is the only FDA-approved treatment for wet AMD proven to improve or maintain vision. In wet AMD clinical trials, Lucentis administered monthly demonstrated an improvement in vision of three lines or more on the study eye chart in up to 41 percent of patients at two years. Nearly all patients (90 percent) in those trials treated monthly with Lucentis maintained vision.
Lucentis is 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. In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula, which is the portion of the eye responsible for fine, detailed central vision.
Lucentis is a prescription medication given by injection into the eye. Lucentis has been associated with detached retina and serious eye infection and should not be used in patients who have an infection in or around the eye. Increases in eye pressure have been seen within one hour of an injection. Although uncommon, conditions associated with eye- and non-eye-related blood clots (arterial thromboembolic events) may occur. Serious side effects included inflammation inside the eye and, rarely, effects related to the injection procedure such as cataract. The most common non-eye-related side effects were nose and throat infection, headache, and respiratory and urinary tract infections. The most common eye-related side effects were the feeling that something is in a patient’s eye, and increased tears. If a patient’s eye becomes red, sensitive to light, painful, or has a change in vision, they should seek immediate care from their eye doctor. Please see the Lucentis Full Prescribing Information on http://www.lucentis.com.
Lucentis was discovered by Genentech and is being developed by Genentech and Novartis for diseases or disorders of the eye. Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a wholly-owned member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
iKlein R., et al. The epidemiology of retinal vein occlusion: The Beaver Dam Eye Study. And Genentech data on file.