Friday, Jun 2, 2006
South San Francisco, Calif. -- June 2, 2006 --Genentech, Inc. (NYSE: DNA) announced today that a Phase IIIb clinical study of a quarterly dosing regimen of the investigational drug Lucentis (ranibizumab) for the treatment of wet age-related macular degeneration (AMD) met its primary efficacy endpoint by preventing vision loss as measured by mean change in visual acuity from baseline to month 12. In this study, called PIER, patients receive Lucentis (0.3 mg or 0.5 mg respectively) or sham injections once per month for the first three months followed thereafter by doses once every three months for a total of 24 months. One-year data from this study were presented today at the Retinal Physician Symposium in the Bahamas. The pivotal Phase III studies of Lucentis (MARINA and ANCHOR) evaluate a monthly treatment schedule.
In the PIER study, patients treated with Lucentis, on average, demonstrated an initial increase in mean visual acuity compared to baseline after three monthly injections. At month three, patients treated with Lucentis, on average, gained 2.9 letters and 4.3 letters (0.3 mg and 0.5 mg dose groups, respectively) compared to a loss of 8.7 letters among patients in the sham group. After the first three monthly injections, patients treated with Lucentis received additional doses at months five, eight and 11. On average, patients treated with Lucentis returned to baseline visual acuity by month 12, while patients in the sham group experienced significant vision loss. At month 12, patients treated with Lucentis lost 1.6 letters and 0.2 letters (0.3 mg and 0.5 mg) compared to a loss of 16.3 letters in the sham group, on average [p less than or equal to 0.0001].
"The results of the Lucentis pivotal studies have changed the expectations for the treatment of wet AMD," said Hal Barron, M.D., Genentech senior vice president, Development and chief medical officer. "While the PIER regimen provided a 16-letter benefit compared to sham, the data suggest that treating patients on a quarterly basis may be less effective than monthly or individualized dosing. Data from ongoing Phase IIIb studies and emerging results from our Investigator Sponsored Trials should help us learn more about the optimal dosing regimen for patients."
Consistent with earlier trials of Lucentis, common side effects that occurred more frequently in the Lucentis groups than in the control group at one year were mild to moderate and included conjunctival hemorrhage, eye pain and increased intraocular pressure. There were no reported cases of endophthalmitis, serious intraocular inflammation or other key ocular serious adverse events. There were no deaths, myocardial infarctions or cerebral vascular events in the first year of the study.
The one-year data from this study were submitted to the U.S. Food and Drug Administration (FDA) for consideration as the FDA reviews the Biologics License Application (BLA).
Additional one-year study findings include:
About the Filing
Genentech submitted a BLA to the FDA for Lucentis on December 29, 2005 and was granted a Priority (six-month) Review. The FDA has until the end of June 2006 to take action on the filing. The submission was based on one-year clinical efficacy and safety data from two pivotal Phase III trials, MARINA and ANCHOR, as well as one-year clinical data from the Phase I/II FOCUS trial. Two-year data from the MARINA study and one-year data from the PIER study were submitted to the FDA after the initial BLA submission. Data from these studies demonstrate that Lucentis is the first investigational therapy to have improved vision in patients with wet AMD in two pivotal Phase III clinical trials. In addition, Lucentis is the first investigational therapy to have demonstrated a clinical benefit compared to verteporfin (Visudyne®) photodynamic therapy (PDT) in a head-to-head clinical study (ANCHOR).
About the Study
PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovasularization with or without Classic CNV Secondary to Age-Related Macular Degeneration) is a study of 184 patients in the United States with predominantly classic, minimally classic or occult with no-classic wet AMD. In this study, patients were randomized 1:1:1 to receive Lucentis (0.3 mg or 0.5 mg) or sham injections once a month for the first three months followed thereafter by doses once every three months for a total of 24 months. Exclusion criteria included prior subfoveal laser treatment, PDT or experimental treatments for wet AMD. Visual acuity was measured using the Early Treatment of Diabetic Retinopathy (ETDRS) chart, the standard method of quantifying visual acuity.
AMD is a major cause of painless central visual loss and is the leading cause of blindness for people over the age of 60. The National Eye Institute estimates that there are 1.7 million people with AMD in the United States alone and that this prevalence will grow to 2.95 million by 2020. AMD occurs in two forms: dry and wet.
The dry form is associated with atrophic cell death of the central retina or macula, which is required for fine vision used for activities such as reading, driving or recognizing faces. The wet form is caused by growth of abnormal blood vessels, also known as choroidal neovascularization (CNV) or ocular angiogenesis, under the macula. These vessels leak fluid and blood and cause scar tissue that destroys the central retina. This results in a deterioration of sight over a period of months to years.
Lucentis (ranibizumab) is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that is believed to play a critical role in angiogenesis (the formation of new blood vessels). Lucentis is designed to block new blood vessel growth and leakiness, which lead to wet AMD disease progression and vision loss. Lucentis is being developed by Genentech and the Novartis Ophthalmics Business Unit for diseases or disorders of the eye. Genentech retains commercial rights in the United States and Canada, and Novartis has exclusive commercial rights for the rest of the world.
About Lucentis Pivotal Phase III Studies
Lucentis has been studied in two randomized, controlled, double-masked Phase III clinical trials. Together, these trials evaluate Lucentis for the treatment of all types of wet AMD.
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD) is a Phase III study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 2:1 to receive intravitreal Lucentis injections or sham injections. Patients treated with Lucentis were further randomized to receive either a 0.3 mg or 0.5 mg dose of Lucentis once a month for two years. Two-year data from this study were presented in May 2006.
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) is a Phase III study comparing two different doses of Lucentis (0.3 mg and 0.5 mg) to Visudyne® in 423 patients. One-year data from this study were presented in January 2006. The trial is ongoing in the United States, Europe and Australia.
At one year in both studies:
At two years, the improvement in vision (as measured by visual acuity endpoints) among patients treated with Lucentis in the MARINA study was maintained while there was further deterioration of vision among patients in the control group. At least 90 percent of those treated with Lucentis at year two maintained or improved vision compared to approximately 53 percent in the control arm.
MARINA Two-Year Safety Profile
Consistent with year-one safety findings, common side effects that occurred more frequently in the Lucentis groups than in the control group at year two were mild to moderate and included conjunctival hemorrhage, increased intraocular pressure and vitreous floaters. Serious ocular adverse events in the MARINA study that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis (cumulative 1.3 percent or less over two years) and intraocular inflammation (cumulative 1.7 percent or less over two years). Among non-ocular serious adverse events, the combined cumulative rate of cerebral vascular events and myocardial infarctions at two years was 3 percent (7/236) in the sham injection group, 4.6 percent (11/238) in the 0.3 mg Lucentis group and 4.2 percent (10/239) in the 0.5 mg group.
ANCHOR One-Year Safety Profile
An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common ocular adverse side effects that occurred more frequently in the Lucentis arms than in the control group were mild to moderate and included conjunctival hemorrhage, increased intraocular pressure, eye pain and vitreous floaters. Serious ocular adverse events that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis and intraocular inflammation (each reported in less than 1 percent of patients per group). Among non-ocular serious adverse events, the frequency of cerebral vascular events was less than 1 percent of patients per group. The frequency of myocardial infarctions was slightly higher in patients treated with 0.5 mg of Lucentis (2.1 percent) than in the other two arms (0.7 percent).
Phase IIIb SAILOR Study
Genentech is enrolling patients with all subtypes of new or recurrent active subfoveal wet AMD in a Phase IIIb study called SAILOR. This study makes Lucentis available to eligible patients in advance of the FDA's decision on the Lucentis BLA. SAILOR (Safety Assessment of Intravitreal Lucentis fOR AMD) is designed to evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for three months and thereafter as needed based on re-treatment criteria. The study is being conducted at more than 100 sites in the United States and will enroll up to 5,000 patients before the FDA's response to the BLA. Those interested in additional information about the study can call toll-free 1-888-662-6728.
Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. In 1989, Napoleone Ferrara, M.D., and a team of scientists at Genentech conducted seminal work in the field, which resulted in the identification and cloning of a gene termed Vascular Endothelial Growth Factor (VEGF), now known as VEGF-A. The VEGF-A protein is believed to play a critical role in angiogenesis and serves as one of the key contributors to physiological or pathological conditions that can stimulate the formation of new blood vessels. The process of angiogenesis is normally regulated throughout development and adult life, and the uncontrolled growth of new blood vessels is an important contributor to a number of pathologic conditions, including wet AMD.
Founded 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products and licenses several additional products to other companies. The company has headquarters in South San Francisco, California and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.