A comparative-effectiveness test of three popular drugs used to treat a common diabetic eye disorder found all three drugs improved eyesight among diabetics with mild vision loss, but the most expensive drug delivered the best outcomes among subjects with the worst vision.
The results of the National Institutes of Health-funded study, published this week in the New England Journal of Medicine, could better inform doctor-patients decisions about treatment for diabetic macular edema, or DME, a condition which affects some 750,000 Americans and for which 7.7 million diabetics are at risk.
Those at risk have a condition called diabetic retinopathy, a disease that can cause abnormal blood vessels to grow in the retina. DME occurs when fluid leaks from those blood vessels and distorts vision in the macula, the part of the retina that looks straight ahead. The three drugs cited in the randomized trial are all injected into the eye and target a substance called vascular endothelial growth factor, or VEGF, which causes the leakage.
The cost of the three drugs varies significantly. Medicare will pay $1,960 for an injection of Regeneron Pharmaceuticals' Eylea (aflibercept); $1,200 for Genentech's Lucentis (ranibizumab); and $70 for Avastin (bevacizumab), also made by Genentech, which is a member of the Roche Group.
The cost of vision-related drug treatments came under scrutiny after the CMS released data on payments made to individual physicians, and many ophthalmologists were found to be among Medicare's highest-paid specialists. A closer look found that a significant portion of their pay was linked to prescribing Lucentis.
The NEJM report showed that all three drugs work, but they work differently.
"The results clearly remove any doubts about anti-VEGF drugs' efficacy in treating DME—all three drugs improved vision substantially,” Dr. Lloyd Aiello, a co-author of the study and a Harvard Medical School professor of ophthalmology, said in a news release. “Physicians now have robust data to help them counsel patients and make informed decisions regarding treatment options."
During the year-long study, patients injected with Avastin and Lucentis received an average of ten injections, while those getting Eylea received an average of nine. Laser treatments had been the common method for treating DME prior to the three drugs' adoption. Laser treatments were performed on patients in the study who had “persistent DME” even after receiving injections. These included 36% of Eylea patients, 46% of those receiving Lucentis, and 56% of Avastin patients.
All patients with mild vision loss—those whose eyesight was measured between 20/32 and 20/40 at the start of the trial—experienced some vision improvement and were able, on average, to read an extra one to two lines on an eye chart, according to the NIH. More significant differences emerged for patients whose eyesight was measured at 20/50 or worse at the trial's start.
Eylea patients in that group were able to read an average of almost four extra lines on the chart, while Lucentis patients improved by almost three lines. The average improvement for Avastis patients was 2.5 lines.
Regeneron trumpeted the results in a news release that quoted its chief scientific officer, Dr. George Yancopoulos. saying how “in this independent, government-funded diabetic macular edema study, Eylea provided significantly greater efficacy, despite fewer injections and fewer laser treatments than comparators.”
Regeneron reported Feb. 10 that 2014 sales of Eylea increased 48% over 2013 to $2.78 billion, including $1.74 billion in the states and $1.04 billion outside the U.S.
“We look forward to another strong year of Eylea growth, driven by expanded use in diabetic macular edema,” Dr. Leonard Schleifer, Regeneron president and CEO, wrote in the company's earnings report. Regeneron also noted that Eylea was approved in November by the Japanese Ministry of Health, Labour, and Welfare for treating DME and last month was recommended for approval by the European Medicines Agency's Committee for Medicinal Products for Human Use.
Dr. Daniel Martin, chairman of the Cleveland Clinic's Cole Eye Institute, and Maureen Maguire, a University of Pennsylvania professor of ophthalmology, wrote an accompanying editorial to the NEJM article describing “powerful forces” that affect physicians' drug choices. These include drug company rebates that reward choosing more expensive drugs and CMS reimbursement policies that provide higher payments to doctors who prescribe more expensive drugs.
“Given the large difference in cost to patients per dose … bevacizumab (Avastin) should be considered as first-line therapy in patients with a visual acuity of 20/40 or better,” Martin and Maguire wrote. “We believe that all financial incentives and logistic barriers to providing the least expensive drug, among drugs equivalent in safety and efficacy, should be eliminated so that patients may benefit fully from the results of this Diabetic Retinopathy Clinical Research Network trial as well as those from other comparative trials.”
The study involved 660 patients with an average age of 61 who received treatments at 89 clinical sites between Aug. 22, 2012 and Aug. 28, 2013. Injections were given every four weeks until vision improved to 20/20 or better. Rates of serious adverse events, hospitalizations and major cardiovascular events among patients were all below 1%.
Regeneron published results of the study (PDF) in October.
Follow Andis Robeznieks on Twitter: @MHARobeznieks