Two Expensive Diabetic Macular Edema Drugs Not Cost-effective

Marcia Frellick

June 09, 2016

Two drugs that are approximately 20 to 30 times more costly than bevacizumab (Avastin, Genentech) are not cost-effective for the treatment of diabetic macular edema (DME) compared with bevacizumab, according to a study published online June 9 in JAMA Ophthalmology.

The two drugs, aflibercept (2 mg; Eylea, Regeneron Pharmaceuticals) and ranibizumab (0.3 mg; Lucentis, Genentech), are both antivascular endothelial growth factor (VEGF) medicines.

Anti-VEGF drugs "revolutionized" treatment for DME, the most common cause of visual impairment in patients with diabetes, write Eric L. Ross, BA, from the Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, and colleagues.

However, the treatments come at a considerable cost, as they may be given nine to 11 times in the first year and an average of 17 times over the course of 5 years. Using 2015 wholesale acquisition costs, the costs per dose compare as follows: aflibercept is $1850, ranibizumab is $1170, and bevacizumab (repackaged at compounding pharmacies into 1.25-mg syringes) is approximately $60.

In the current study, the researchers calculated the incremental cost-effectiveness ratios (ICERs) of the three drugs. One-year trial data were used to calculate cost-effectiveness for 1 year for the three anti-VEGF drugs. Then the researchers used mathematical modeling to project 10-year cost-effectiveness.

They found that treatment costs of aflibercept and ranibizumab would have to drop by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100,000 per quality-adjusted life-year (QALY) compared with bevacizumab over the course of a 10-year period.

"For all participants, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per QALY and $1 730 000 per QALY, respectively," according to the article.

For a subgroup that had worse baseline vision, the ICERs were $1,870,000 per QALY and $2,450,000 per QALY, the authors found.

"From a societal perspective, bevacizumab as first-line therapy for DME would confer the greatest value, along with substantial cost savings vs the other agents," the authors conclude. In 2013, Medicare Part B expenditures for aflibercept and ranibizumab added up to $2.5 billion.

But for physicians and patients, the choice is more complex.

Weighing Drawbacks and Benefits

One coauthor, Lee Merrill Jampol, MD, professor of ophthalmology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, said there are several considerations.

One is that bevacizumab, a cancer drug, is not approved for DME, and in some countries or regions, its use is not allowed. Where bevacizumab is not allowed, aflibercept is not cost-effective relative to ranibizumab, the authors write.

Another consideration is that bevacizumab is not available in a single-dose form for injection in the eye, so it must be compounded into syringes from larger vials, which introduces the possibility for contamination.

"There have been compounding mistakes by pharmacies in the United States and elsewhere," Dr Jampol told Medscape Medical News. "People have gotten infections in the eye, but also in the spinal cord and other places."

Although incidences are rare, he said, "I think it's a real concern." He said patients and physicians should make sure the compounding is done by a safe, guaranteed pharmacy that has the proper equipment.

In addition, "You have to weigh the fact that in some cases [bevacizumab] is not as effective as the more expensive drugs," he said.

As previously reported by Medscape Medical News, a study coauthored by Dr Jampol found that aflibercept was more effective in patients with worse levels of initial visual acuity.

"At the end of 2 years the Eylea was still more effective than the Avastin, and the difference with Lucentis had narrowed, but was still there," Dr Jampol said.

"If the vision is 20/50 or worse in the eye, then Eylea has an advantage," he said. "If the vision is 20/40 or better...we found that the three drugs were the same."

Researchers have not determined how the drugs compare after 2 years, although they say it is unlikely that any differences in visual acuity achieved with the three agents during years 2 to 10 (the range of changes seen in previous studies) would change their relative cost-effectiveness.

"These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results," the authors write.

This study was supported by a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. Various coauthors report receiving grants from Jaeb Center for Health Research, the National Institutes of Health, Regeneron, and Genentech/Roche during the conduct of the study and grants from Bayer and Novartis outside the submitted work. A complete list of all Diabetic Retinopathy Clinical Research Network ( financial disclosures can be found at

JAMA Ophthalmol. Published online June 9, 2016. Full text

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