Two Phase III Lucentis studies show promise for RVO

October 14, 2009

Two Phase III studies of Lucentis (ranibizumab injection) in macular oedema due to retinal vein occlusion (RVO), have shown, 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 at the Retina Congress 2009 meeting.

Two Phase III studies of Lucentis (ranibizumab injection) in macular oedema due to retinal vein occlusion (RVO), have shown, 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 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, MD, 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 (FVF4165g) BRAVO is a multicentre, randomized, double-masked, sham injection-controlled Phase III study of 397 patients designed to assess the safety and efficacy profile of Lucentis in macular oedema 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 (FVF4166g) CRUISE is a multicentre, 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.

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.