Friday, Mar 25, 2011

Second Lucentis Phase III Study Meets Primary Endpoint for Improved Vision in Patients with Diabetic Macular Edema (DME)

Results Consistent with Data Released Last Month Showing Patients with DME Who Received Lucentis Achieved Significant Improvement in Vision

South San Francisco, Calif. -- March 25, 2011 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the second of two Phase III trials evaluating Lucentis® (ranibizumab injection) in patients with diabetic macular edema (DME) met its primary endpoint. The primary endpoint of the study, known as RIDE, showed that after 24 months a significantly greater number of patients who received Lucentis, compared to those who received placebo (sham) injections, were able to read at least 15 additional letters on an eye chart than they could at the start of the study. The safety results were consistent with previous Lucentis Phase III trials and no new significant safety findings were observed. Further analyses of the data are ongoing. Topline results from the RIDE study will be presented at the EURETINA Congress in London on May 29, 2011.

DME is an eye condition characterized by swelling of the retina, which can occur in patients with type 1 or type 2 diabetes and can cause blurred vision, severe vision loss and blindness.1 DME is a leading cause of blindness among the working-age population in most developed countries,2 and there are currently no U.S. Food & Drug Administration (FDA) approved medications to treat DME.

"This data adds to the considerable body of clinical evidence showing that patients with DME who received Lucentis had significant improvement in vision," said Hal Barron, M.D., chief medical officer and head, Global Product Development. "Lucentis may provide physicians and patients with a potential option for DME, and we look forward to sharing the data from this study and a previous Phase III trial with the FDA and medical community."

In February, Genentech announced that the RISE study, the first of the two Phase III studies evaluating Lucentis in patients with DME, had met the same primary endpoint. Topline results from RISE were presented March 10 at the Macula Society Meeting and showed that patients with DME who received Lucentis experienced rapid and sustained improvement in vision beginning at day seven, which was sustained at 24 months. RIDE and RISE are identical Phase III studies designed to support a marketing application to the FDA for a potential new indication for Lucentis in DME.

RIDE Study Results
At 24 months, 33.6 percent of patients (42/125) who received 0.3 mg Lucentis and 45.7 percent of patients (58/127) who received 0.5 mg Lucentis were able to read at least 15 more letters on the eye chart than they were at baseline, compared to 12.3 percent of patients (16/130) who received sham injections. The difference between each Lucentis dose group and the sham injection group was statistically significant. The study was not designed to compare the Lucentis doses with each other.

In the study, changes in vision were measured by best-corrected visual acuity (BCVA), which is the best possible vision a person can achieve with corrective lenses, based on reading a standardized eye chart.

Key secondary endpoints met statistical significance and included average eye chart reading scores over time and changes in retinal swelling.

Safety
A preliminary analysis of the 24-month data from the RIDE study showed an ocular and systemic safety profile consistent with previous Lucentis Phase III trials.

Common ocular adverse events that occurred more frequently in the Lucentis dosing groups than in the sham injection group included conjunctival hemorrhage, eye pain, eye irritation, vitreous floaters, retinal exudates and increased intraocular pressure.

Patients receiving Lucentis in the RIDE study experienced fewer adverse events associated with diabetic retinopathy compared with the sham injection group including vitreous hemorrhage, retinal neovascularization and iris neovascularization.

Among non-ocular or systemic serious adverse events in the RIDE study, 1.6 percent of patients in the sham injection group, 1.6 percent of patients in the 0.3 mg Lucentis dose group and 2.4 percent of patients in the 0.5 mg Lucentis dose group had a stroke (cerebrovascular accident). A total of 4.7 percent of patients in the sham injection group, 5.6 percent of patients in the 0.3 mg Lucentis dose group and 2.4 percent of patients in the 0.5 mg Lucentis dose group experienced a heart attack (myocardial infarction). Two patients in the sham injection group, four patients in the 0.3 mg Lucentis dose group and six patients in the 0.5 mg Lucentis dose group died during the study. Three of the six deaths in the 0.5 mg Lucentis dose group were from non-vascular causes.

About RIDE
RIDE is a multicenter, randomized, double-masked, sham injection-controlled, 36-month (sham injection-controlled for 24 months) Phase III study designed to assess the efficacy and safety profile of Lucentis in 382 patients with DME. Patients were randomized to receive monthly injections of either 0.3 mg Lucentis (n=125), 0.5 mg Lucentis (n=127) or monthly sham injections (n=130). The RIDE study was not designed to compare the two doses of Lucentis, but each dose against the sham injection group.

Beginning at three months, macular laser rescue treatment was made available to all patients, if needed, based on pre-specified criteria. After month 24, patients in the sham injection group were eligible to receive monthly injections of 0.5 mg Lucentis, and all patients will continue to be followed and dosed monthly for a total of 36 months. The study then continues in an open-label extension phase.

About DME
DME is swelling of the retina that occurs in people with diabetes, who suffer from a complication called diabetic retinopathy. Diabetic retinopathy is the most common diabetic eye disease and is characterized by damage to the blood vessels of the retina, the nerve layer at the back of the eye.1 In DME, the damaged blood vessels leak fluid into the central portion of the retina, called the macula, causing it to swell. The macula is the part of the eye responsible for sharp central vision.1 The fovea is at the center of the macula.

Approximately 26 million people in the U.S. have diabetes, and 1.9 million new cases are diagnosed in people aged 20 and older each year.3 Up to 10 percent of all people with diabetes will develop DME during their lifetime, and up to 75,000 new cases of DME are estimated to develop each year.4

The current standard of care for DME is laser surgery that helps seal the leaky blood vessels to slow the leakage of fluid and reduce the amount of fluid in the retina.1,5

About Lucentis
Lucentis is a vascular endothelial growth factor (VEGF) inhibitor which was first approved by the FDA for the treatment of neovascular (wet) age-related macular degeneration (AMD) in June 2006. Lucentis was also approved by the FDA for macular edema following retinal vein occlusion (RVO) on June 22, 2010. Lucentis was approved in 2011 for treatment of visual impairment due to DME in Europe, where it is marketed by Novartis.

Lucentis is designed to bind to and inhibit VEGF, 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 wet AMD, these blood vessels grow under the retina and leak blood and fluid, causing rapid damage to the macula. In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula.

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.

In two Phase III clinical trials studying macular edema following RVO, both studies showed that Lucentis administered monthly demonstrated an early (day seven) and sustained vision improvement of three lines or more on the study eye chart during the six-month study.

Lucentis Safety
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. Lucentis should not be used in patients who have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.

Although not common, Lucentis patients have had eye- and non-eye-related blood clots (heart attacks, strokes and death). Some patients have increases in eye pressure within one hour of an injection. Serious side effects include inflammation inside the eye and, rarely, problems related to the injection procedure, such as developing a cataract. These can make a patient's vision worse. The most common side effects to the eye are increased redness in the whites of the eye, eye pain, small specks in vision and the feeling that something is in the eye. The most common non-eye-related side effects are nose and throat infections, headache and respiratory (lung) infections. If a patient's eye becomes red, sensitive to light, painful or there is a change in vision, patients should call or visit their eye doctor right away.

Please visit http://www.lucentis.com for the Lucentis full prescribing information and additional important safety information.

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

About Genentech
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 member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

References:

1National Eye Institute. Health Information. Available at: http://www.nei.nih.gov/health/diabetic/retinopathy.asp.

2Ciulla TF, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening and novel therapies. Diabetes Care. 2003;26:2653-2664.

3American Diabetes Association. Statistics. Available at: http://www.diabetes.org/diabetes-statistics.jsp.

4Ali, F.A. A review of diabetic macular edema. Digital Journal of Ophthalmology, vol. 3, no. 6, 1997. Available at: http://www.djo.harvard.edu/site.php?url=/physicians/oa/387.

5Macular Edema, Diabetic; emedicine from WebMD, Medscape Specialties: Opthalmology/Retina; Updated: Oct 7, 2010. Available at: http://emedicine.medscape.com/article/1224138-overview.