SAILOR Points to Good Safety Profile for Ranibizumab
One-year data on the phase 3b SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) trial showed the drug was safe and was not associated with higher rate of stroke, according to principal investigator David S. Boyer, MD, at Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration 2008 meeting in Key Biscayne, Florida.
The study included approximately 4,300 patients with all subtypes of new or recurrent active subfoveal wet age-related macular degeneration (AMD) who were treated with 0.3 mg or 0.5 mg doses of intravitreal ranibizumab (Lucentis, Genentech). Results were based off of information gathered from cohort 1, which included 2,378 patients.
These data come almost 1 year after Genentech issued a letter to physician-users (a so-called "Dear Doctor" letter) in January 2007, noting safety concerns in the interim safety analysis of SAILOR. That preliminary data showed a four-fold difference in the rate of strokes in the group receiving the 0.5-mg (1.2%) than in the group receiving the 0.3-mg dose (0.3%) at an average follow-up of 230 days. Patients with previous history of stroke appeared to be at higher risk for stroke during the trial.
One-year results, however demonstrated that although the US Food and Drug Administration (FDA) approved dose of Lucentis (0.5 mg) trended toward a higher incidence of stroke (1.2% vs. 0.7% in the 0.3 mg dose group) the results were not statistically significant (P=.21). The stroke rate in the general US population (65 years of age or older) is 1.4%, according to Anne E. Fung, MD, who presented at the same meeting on the rates of arterial thromboembolic events in Medicare patients.
"I think that we over-analyzed the 6-month data; perhaps it was blown a bit out of proportion in comparison to all of the other studies out there at the time," Dr. Boyer said in a telephone interview with Retina Today. "Genentech reported the 6-month data, as it should have. But I think that [the results of SAILOR] are one of the reasons you wait for a year to get the complete data. We now see that there was no probable statistical significance — the numbers just caught up by the end of the trial. If we examined the data for a longer period of time, those numbers for the two dosing groups might even come closer in line to each other."
As SAILOR was a 1-year study, there are no further plans to continue the trial, Genentech spokeswoman Krysta Pellegrino told Retina Today. Results for the second SAILOR cohort (approximately 1,900 patients), however, will be available sometime this year.
Cost-containment Strategies Necessary for AMD Treatment
Breakthrough treatments have resulted in the sharp escalation of costs for AMD therapy when compared with standard therapy, but there are several promising areas for cost containment, said William E. Smiddy, MD. He presented the results of his study of the cost/line-year analysis of AMD treatments at the Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration 2008 meeting.
According to the study, the cost/line-year of monthly dosing of ranibizumab (Lucentis, Genentech) is highly disproportionate to the cost/line-year of standard therapy (photodynamic therapy [PDT]) and the comparable bevacizumab (Avastin, Genentech).
The gap between costs for these therapies remains disproportionate even when reduced treatment schedules are utilized because of the high cost of ranibizumab. Combination therapies, such as PDT and steroids and triple and quadruple therapies, may offer a reduced cost burden to physicians and patients. Results of clinical trials currently underway to evaluate combination therapy and the comparability of ranibizumab vs bevacizumab will help to map future strategy. The goal, said Dr. Smiddy, is to find possible areas of cost containment and lower treatment burden without losing the quality of treatment outcomes.
"The strategies that are seemingly most promising are currently utilizing less expensive antivascular endothelial cell growth factor (anti-VEGF) agents or combination therapies, but there are other areas where we can look for solutions to achieve cost containment without loss of quality," Dr. Smiddy said.These areas include less frequent dosing schedules, as-needed dosing, a reduction in drug costs, and new methods of drug delivery.
Twice the Risk of Heart Attack and Stroke Mortality for Patients with AMD
A new study published in the online version the British Journal of Ophthalmology finds a link between AMD and a higher risk for death following stroke and heart attack. The study enrolled 3,654 total patients, 49 years of age or older. Over the course of 10 years, patients were examined, and it was determined that patients who were younger than 75 years of age with early-stage AMD had twice the risk death from heart attack or stroke than patients without AMD. Patients who had late-stage AMD had an even higher risk: For heart attack, the risk of death was fivefold and for stroke the risk was tenfold.
Paul L. Mitchell, MD, lead investigator on the study, wrote that the vascular nature of the disease and risk factors that the AMD shares with cardiovascular disease, such as smoking and hypertension, may be why the risk of heart attack and stroke increases with age and progression of AMD.
NIH Launches Lucentis, Avastin Comparison Trials
The National Eye Institute (NEI) of the National Institute of Health (NIH) announced the start of a multicenter clinical trial to compare the relative safety and effectiveness of ranibizumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech).
"This clinical trial will evaluate whether the treatment burden for patients can be reduced without compromising effectiveness," said Paul A. Sieving, MD, PhD, Director of the NEI.
The Lucentis — Avastin Trial (CATT) will monitor the outcomes of 1,200 patients who will be treated with either:
- Injection of either bevacizumab or ranibizumab on a fixed schedule of once every 4 weeks for 1 year, with the patient randomly assigned to either an injection of Lucentis every 4 weeks, or on a variable schedule depending on their response to treatment, in the second year; or
- The injection of either bevacizumab or ranibizumab on a variable schedule.
The primary outcome measure will be change in visual acuity. Secondary outcome measures will include number of treatments, anatomical changes in the retina, adverse events, and cost.
The clinical trial will be conducted at 47 clinical centers across the country. For a list of enters, eligibility recruitments, and other information, go to: www.nei.nih.gov/CATT.
Phase 3 VEGF Trap-Eye for AMD Shows Promise
Data from the VIEW 1 study (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) were presented by Quan Dong Nguyen, MD, MSc, at the Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration 2008 meeting. The VEGF Trap-Eye (Regeneron Pharmaceuticals) has a high affinity for binding VEGF — greater than the affinity of either native receptor alone, in a molecule that is smaller than an antibody and penetrates all layers of the retina, according to Dr. Nguyen.
At the completion of the phase 1 study, the VEGF Trap-Eye demonstrated safety tolerability, and bioefficacy in eyes with neovascular AMD, as well as eyes with diabetic macular edema, Dr. Nguyen said. Additionally, dose response was demonstrated, with 2- and 4-mg doses showing more bioactivity than lower doses studied. The duration of that effect appears to be at least 8 weeks.
After reviewing the results of this and two other studies (ie, CLEAR-IT AMD 1 and CLEAR-IT 2 [Clinical Evaluation of Antiangiogenesis in the Retina Intravitreal AMD Clinical Trials]) researchers found no drug-related serious adverse events, and that the treatment of the VEGF Trap-Eye was generally well tolerated.
VEGF Trap-Eye met the primary endpoint of a statistically significant mean reduction in retinal thickness after 12 weeks compared with baseline, and quarterly dosing demonstrated (on average) a decrease in excess retinal thickness and an increase in visual acuity, Dr. Nguyen said.
Future studies to further determine the VEGF Trap-Eye's role as a therapy for choroidal neovascularization and retinal vascular diseases are the in the planning stages.
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