CRUISE Phase III trial results: Ranibizumab safe, effective for macular edema

New York-Safety and efficacy analyses based on 6-month data collected in CRUISE, a prospective, randomized, sham-controlled, double-masked phase III trial, indicate a tremendously promising role of anti-vascular endothelial growth factor therapy with intravitreal ranibizumab (Lucentis, Genentech) in the treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO), said David M. Brown, MD, at the 2009 Retina Congress. He is director of clinical research at Retina Consultants of Houston and an attending retina surgeon at The Methodist Hospital in Houston.

Mean change in best corrected visual acuity (BCVA) from baseline to 6 months represents the primary efficacy endpoint for the phase III trial, and the results showed a clinically and statistically significant benefit of ranibizumab treatment compared with the control group. At month 6, patients receiving ranibizumab 0.3 mg and 0.5 mg experienced mean BCVA gains from baseline of 12.7 letters and 14.9 letters, respectively, compared with 0.8 letters for the control group.

Of particular note, at 6 months, almost half of the patients in the ranibizumab 0.3 mg (46.2%) and 0.5 mg (47.7%) groups achieved a BCVA improvement of at least 15 letters compared with 16.9% of those in the control group, Dr. Brown said.

The 1-year trial is ongoing, but after the primary endpoint at 6 months, patients who received sham treatment became eligible to receive ranibizumab 0.5 mg, whereas patients receiving ranibizumab will continue with their original treatment assignment. All injections, however, will be administered on an as-needed basis according to protocol-specified OCT and VA criteria.

Favorable safety profile

The 6-month data from CRUISE together with results from a phase III study of ranibizumab for treatment of branch RVO (BRAVO) will form the basis of a supplemental biologics license application being submitted to gain FDA approval.

"The favorable safety profile seen at 6 months combined with the overwhelming improvements achieved in vision and OCT measurement of ME suggest all existing treatments for CRVO will be relegated to second-line status," Dr. Brown said. "However, while the responses to ranibizumab are amazing and the data seem to speak for themselves, determining the place of ranibizumab in patient care will ultimately depend on whether the safety and efficacy demonstrated so far are validated by the 12-month data."

The CRUISE patient population had an average age of about 68 years, just over half were males, and about 85% were Caucasian. In all three treatment arms, mean BCVA at study entry was about 20/100 and mean central foveal thickness was about 670 µm.

At day 7, both ranibizumab groups had a mean BCVA gain of almost 2 lines (~9 letters) compared with a 1.1-letter gain in the sham-treated group. In both ranibizumab groups, central foveal thickness was reduced by about 400 µm at 7 days and about 440 µm by month 6. Central foveal thickness also decreased in the sham-treated group, but the improvement in edema occurred more gradually and the net change was about 165 µm at 6 months.

Adverse events

The ocular and systemic safety data in CRUISE reflected the results collected in the MARINA and ANCHOR pivotal trials of ranibizumab for the treatment of choroidal neovascularization secondary to age-related ME, Dr. Brown said.

"The safety review showed that two patients in each ranibizumab arm had worsening of an existing cataract. Rates of other ocular side effects were higher in the sham arm than in the ranibizumab groups," he said.

A single serious ocular adverse event occurred in the sham injection group, a case of vitreous hemorrhage, but no serious ocular adverse events occurred in any patients treated with ranibizumab. One patient in each treatment arm experienced a nonocular serious adverse event, either myocardial infarction or acute coronary syndrome.