CLINICAL TRIAL SPOTLIGHT

CATT Study Begins Enrolling

Ranibizumab vs bevacizumab in head-to-head comparison.

JERRY HELZNER, SENIOR EDITOR

On Feb. 1, investigators at more than 40 sites around the United States began enrolling the first of what ultimately will be approximately 1200 patients in the much-awaited Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) study.

The study is designed to determine whether there is any significant difference in efficacy and safety between FDA-approved ranibizumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech), an approved colorectal cancer therapy that has been widely used by retina specialists off-label to treat the wet form of AMD.

There have been many calls for such a study due to the fact that Lucentis costs approximately $1,950 an injection and Avastin can be given for less than $100 per treatment.

Genentech is not participating in the study. The company has taken the position that ranibizumab is FDA-approved, effective, and available, thus negating any need for the company to delve further into the usage of off-label alternatives.

INCLUSION CRITERIA

The 2-year, phase 3 study is being funded by the National Institutes of Health (NIH) at a cost of about $16 million. The study will include patients over 50 years of age with active subfoveal choroidal neovascularization (CNV) and subretinal hemorrhage and fibrosis over less than 50% of the total lesion area. Patients' visual acuity at baseline must fall in a range between 20/25 and 20/320 and they must have at least 1 drusen in either eye or late-stage AMD in the fellow eye.

The NIH provided the following justification for undertaking the CATT study:

"Ranibizumab (Lucentis) is the most effective treatment for neovascular AMD studied to date. Bevacizumab (Avastin) and ranibizumab are derived from the same monoclonal antibody. Following the encouraging clinical trial results with ranibizumab, several investigators began evaluating intravitreal bevacizumab for the treatment of CNV. Given its molecular similarity to ranibizumab, its low cost, and its availability, the interest in bevacizumab has been considerable. Bevacizumab has not been evaluated relative to ranibizumab.

"In addition, previous studies do not answer the question of whether a reduced dosing schedule is as effective as a fixed schedule of monthly injections. Treatment dependent on clinical response has the potential to reduce the treatment burden to patients as well as to reduce the overall cost of therapy."

The prime outcome measure of the CATT study is to determine the mean change in visual acuity (VA) for both ranibizumab and bevacizumab.

Secondary outcome measures include: number of treatments required; number of patients demonstrating a 3-line change in VA; change in subretinal and intraretinal fluid as shown by optical coherence tomography (OCT); change in lesion size as shown by fluorescein angiography; incidence of endophthalmitis, retinal detachment, cataract, and uveitis; incidence of adverse events, and cost.

STUDY IN 4 ARMS

The CATT study has been broken down into 4 distinct arms. According to the NIH, 1 group will be given 0.5 mg ranibizumab injections every 4 weeks for 1 year and then be re-randomized to either repeat the same schedule or receive variable dosing determined by signs of lesion activity. A second group will receive 1.25 mg bevacizumab every 4 weeks for 1 year and then be re-randomized to either the same schedule or variable dosing determined by signs of lesion activity. The other 2 groups would get either 0.5 mg ranibizumab or 1.25 mg bevacizumab on an as-needed basis for 2 years, with retreatments determined by signs of lesion activity.

In the recently completed PrONTO study using only ranibizumab, the use of OCT measurements to determine retreatment resulted in most patients requiring approximately 5 to 6 injections per year.

Before ranibizumab won approval in June 2006, numerous retina specialists who followed pioneering studies conducted by Philip Rosenfeld, MD, PhD, of the Bascom Palmer Eye Institute, began using bevacizumab to treat wet AMD. Since ranibizumab was approved, many doctors have switched to that drug, particularly for patients with good insurance coverage. RP