Basel, 10 March 2011
Phase III study of Lucentis showed rapid vision improvements sustained for two years in patients with diabetic macular edema
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that two-year results from a pivotal Phase III trial (RISE) showed patients with diabetic macular edema (DME) who received Lucentis® (ranibizumab injection) experienced rapid and sustained improvement in vision compared to those who received a placebo (sham) injection. According to the data, there was:
- A significantly greater number of people able to read at least 15 additional letters on the eye chart compared to baseline after 24 months (primary endpoint),
- Significant improvement in average eye chart reading scores at 24 months,
- Significant improvement in average eye chart reading scores demonstrated as early as seven days,
- Significantly decreased retinal swelling.
“There are no FDA-approved medicines to treat DME and these new data add to evidence showing that Lucentis can help improve vision soon after initiation of treatment,” said Dennis M. Marcus, M.D., Southeast Retina Center in Augusta, Ga., who presented the data today. “In the case of the RISE study, the significant improvements on day seven were maintained for two years.”
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 The safety results were consistent with previous experience and no new adverse events related to Lucentis were observed in the study.
The data from RISE, the first of two pivotal Phase III studies of Lucentis in DME, were presented today at the 34th Annual Macula Society Meeting in Boca Raton, Fla.
At 24 months, 44.8 percent of patients (56/125) who received 0.3 mg Lucentis and 39.2 percent of patients (49/125) who received 0.5 mg Lucentis were able to read at least 15 more letters on the eye chart than they were at the start of the study, compared to 18.1 percent of patients (23/127) who received sham injections. The difference between each Lucentis dose group and the sham injection group was statistically significant.
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 endpoint data presented include:
- At 24 months, patients receiving 0.3 mg Lucentis had a mean gain in BCVA of 12.5 letters from baseline and patients receiving 0.5 mg Lucentis had a mean gain of 11.9 letters, compared with a mean gain of 2.6 letters for the sham injection group.
- As early as seven days (first post-baseline time point), patients receiving Lucentis demonstrated a statistically significant mean gain in BCVA: 5.4 letters for the 0.3 mg group and 4.6 letters for the 0.5 mg group, compared with 1.6 letters in the sham injection group. Improvements in BCVA in the Lucentis groups over the sham injection group were statistically significant at all time points between seven days and 24 months.
- The study also evaluated changes in retinal anatomy, including central foveal thickness. At 24 months, patients receiving 0.3 mg and 0.5 mg Lucentis showed a mean decrease of 250.6 microns and 253.1 microns from baseline, respectively, in central foveal thickness compared to a mean decrease of 133.6 microns in the sham injection group. Statistically significant improvements in the Lucentis groups over the sham injection group were noted at just one month after dosing (first tested time point) and were observed at all evaluated time points over the 24-month period.
Central foveal thickness was measured using an optical coherence tomography scan, which provides a cross-sectional image of the retina and can help identify and evaluate characteristics of the retina and macula, such as thickness and the presence or absence of swelling (edema).
An analysis of the 24-month data from the RISE study showed a 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 control group included conjunctival hemorrhage, eye pain, eye irritation, vitreous floaters, foreign body sensation in the eye and increased intraocular pressure. Serious ocular events occurring in the RISE study included one case of endophthalmitis, one retinal tear and two traumatic cataracts in the Lucentis groups.
Patients receiving Lucentis experienced fewer adverse events associated with diabetic retinopathy including retinal neovascularization (13.8 percent in the sham injection group, 0.8 percent in the 0.3 mg Lucentis dose group and 4.0 percent in the 0.5 mg Lucentis dose group), vitreous hemorrhage (13 percent in the sham injection group and 3.2 percent in each of the Lucentis dose groups) and retinal hemorrhage (20.3 percent in the sham injection group, 12.8 percent in the 0.3 mg Lucentis dose group and 12.7 percent in the 0.5 mg Lucentis dose group).
Preliminary analysis indicates no new findings related to non-ocular or systemic safety. The incidence of serious adverse events potentially related to systemic VEGF inhibition was 10.6 percent of patients in the sham injection group, 5.6 percent of patients in the 0.3 mg Lucentis dose group and 11.9 percent of patients in the 0.5 mg Lucentis dose group. Among non-ocular serious adverse events in the RISE study, 1.6 percent of patients in the sham injection group, 0.8 percent of patients in the 0.3 mg Lucentis dose group and 4.0 percent of patients in the 0.5 mg Lucentis dose group had strokes (cerebrovascular accidents). A total of 2.4 percent of patients in the sham injection group, 1.6 percent of patients in the 0.3 mg Lucentis dose group and 3.2 percent of patients in the 0.5 mg Lucentis dose group experienced a heart attack (myocardial infarction). A total of 0.8 percent of patients in the sham injection group, 2.4 percent of patients in the 0.3 mg Lucentis dose group and 4.0 percent of patients in the 0.5 mg Lucentis dose group died during the study.
RISE 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 of Lucentis in 377 patients with DME. Patients were randomized to receive monthly injections of either 0.3 mg Lucentis (n=125), 0.5 mg Lucentis (n=125) or monthly sham injections (n=127). The RISE study was not designed to compare the two doses of Lucentis, but each dose against the control 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 control 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.
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 vision1. The fovea is at the center of the macula.
Approximately 26 million people in the United States (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
Lucentis is a vascular endothelial growth factor (VEGF) inhibitor which was first approved by the U.S. Food & Drug Administration (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. RISE and a second pivotal trial, RIDE, are two identical, parallel confirmatory studies designed to support application to the FDA for a potential new indication for Lucentis for DME. The results from RIDE are expected later in 2011.
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 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.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80’000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
1) National Eye Institute. Health Information. Available at: http://www.nei.nih.gov/health/diabetic/retinopathy.asp.
2) Ciulla TF, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening and novel therapies. Diabetes Care. 2003;26:2653-2664.
3) American Diabetes Association. Statistics. Available at: http://www.diabetes.org/diabetes-statistics.jsp.
4) Ali, 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.
5) Macular Edema, Diabetic; emedicine from WebMD, Medscape Specialits: Opthalmology/Retina; Updated: Oct 7, 2010. Available at: http://emedicine.medscape.com/article/1224138-overview.
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