Eylea Maintains VA Gains at 96 Weeks
But reduced-dosing advantage ebbs in second year.
■ Regeneron Pharmaceuticals and Bayer HealthCare said that in an integrated two-year analysis of the VIEW 1 and VIEW 2 phase 3 studies comparing their 2 mg Eylea therapy for the treatment of wet AMD with 0.5 mg Lucentis, patients treated with Eylea averaged needing five fewer injections over 96 weeks than patients treated with Lucentis. However, the need for retreatment was almost the same for both drugs in the second year, except for those patients who required the most intense therapy.
The Eylea 2 mg every eight weeks regimen was recently approved by the FDA.
In the second year of the studies, patients were treated with the same dose per injection as in the first year and were evaluated monthly to determine need for retreatment. Patients were treated at least every 12 weeks. All year 2 analyses were considered exploratory.
In the integrated analysis of the 2,400-patient VIEW 1 and VIEW 2 studies, the visual acuity gain from baseline in the Eylea 2 mg every eight week group at week 96 was 7.6 letters compared to 8.4 letters at week 52, with an average of 11.2 injections over two years and 4.2 injections during the second year. The visual acuity gain from baseline in the monthly Lucentis group at week 96 was 7.9 letters compared to 8.7 letters at week 52, with an average of 16.5 injections over two years and 4.7 injections during the second year. The results of each of the VIEW 1 and VIEW 2 studies were consistent with the integrated analysis.
The overall fewer average number of injections in the second year in the Eylea 2 mg every eight week group compared to the Lucentis group (4.2 vs 4.7) was driven by the fact that fewer patients needed more intense therapy in the Eylea group and those patients required fewer injections.
The proportion of patients who required frequent injections (six or more) during the second year was lower in the Eylea 2 mg every eight week group compared to the Lucentisgroup (15.9% vs 26.5%). In the 25% of patients who required the greatest number of injections, patients in the Eylea 2 mg every eight week group required an average of 1.4 fewer injections in the second year compared to the Lucentis group (6.6 vs 8.0). In the 25% of patients in each group who had the fewest number of injections in the second year, the average number of injections was similar (approximately three for both groups, corresponding to the protocol-mandated minimum number of injections).
A generally favorable safety profile was observed for both Eylea and Lucentis. The incidence of ocular treatment-emergent adverse events was balanced across all treatment groups in both studies, with the most frequent events associated with the injection procedure, the underlying disease and/or the aging process. The most frequent ocular adverse events (>10% of patients for the overall study population) were conjunctival hemorrhage, eye pain, retinal hemorrhage and reduced visual acuity.
The most frequent serious nonocular adverse events were typical of those reported in this elderly population who receive intravitreal treatment for wet AMD; the most frequently reported events (greater than 1% of patients for the overall study population) were falls, pneumonia, myocardial infarction and atrial fibrillation. There were no notable differences among the study arms. The incidence of arterial thrombotic events as defined by the “Anti-Platelet Trialists” group criteria was 3.2% of patients for Lucentis and 3.3% of patients in the combined Eylea groups.
“These second-year results confirm the sustainability of the vision gains achieved by Eylea with a less than monthly dosing frequency Importantly, the second-year data demonstrated that for patients who needed more anti-VEGF treatment, this was achieved with fewer injections using Eylea,” said George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Laboratories.
The recommended dose for Eylea is 2 mg every eight weeks following three initial monthly injections, which demonstrated acuity gains approximately clinically equivalent to monthly Lucentis. Eylea is priced at $1,850 per dose — $100 below Lucentis, despite its more durable response.
Rising Medicare Costs for Wet AMD
Study examines per-patient payments in 1994 and 2006.
■ Researchers from the Duke Eye Center and Duke's Department of Economics have combined to attempt to quantify the increasing burden to Medicare for wet AMD by comparing per-patient costs prior to the introduction of anti-VEGF therapy to per-patient expenditures in a year in which anti-VEGF treatment was available.
In an article appearing in the December 2011 online edition of the American Journal of Ophthalmology, the researchers compared average perpatient Medicare costs from the 1994 wet AMD cohort to average costs from a matched sample of 2006 patients. The researchers note that new diagnoses of wet AMD more than doubled between 1994 and 2006.
Given that treatment options for wet AMD in 1994 were limited, the average per-patient cost to Medicare for eye care was $1,504. The average per-patient cost for eye care for the 2006 sample was $3,263. The researchers found that much of the increase for the latter year was due to anti-VEGF injections, increased number of visits and imaging studies. Anti-VEGF injections alone accounted for an average of $1,609 in Medicare perpatient payments in 2006.
Though the researchers noted the “remarkable clinical benefits” associated with the introduction of anti-VEGF treatment for wet AMD, they also assert that the increasing number of patients diagnosed with wet AMD, combined with the cost of administering anti-VEGF therapy, is placing a much greater financial burden on Medicare.
It should also be noted that 2006 was one of the first years in which anti-VEGF injections for wet AMD were available, so the figures for perpatient Medicare costs compiled by the Duke researchers may be low in comparison to succeeding years.
Microvascular Changes Predict Disability
Retinal disease linked to later functional impairment.
Samantha Stahl, Assistant Editor
■ Vascular diseases could be an early indicator for disability later in life, according to a recent study.
Researchers led by Dae Hyun Kim, MD, at the Beth Israel Deaconess Medical Center in Boston reported in Archives of Ophthalmology that people with two or more retinal signs were 45% more likely to develop functional impairment, reducing their ability to perform day-to-day activities.
The researchers did not find a direct association with any one sign, but noted that vascular disease, including lesions in large and small vessels, is linked to executive dysfunction. A cross-sectional analysis revealed that a higher burden of retinal signs was connected to worse mental and physical functioning.
Dr. Kim and colleagues looked at the Cardiovascular Health Study, a population-based cohort study of cardiovascular disease in nearly 6,000 older adults that began in 1989. Between 1997 and 1998, 1,998 study participants underwent retinal photography and measurement of the retinal arteriolar and venular caliber, retinopathy, arteriovenous nicking and focal arteriolar narrowing.
Of the patients without disability or missing information (1,487 participants), the researchers found that the prevalence of retinopathy, arteriovenous nicking and focal arteriolar narrowing was 7.1%, 7.5% and 0.4%, respectively. Patients with two or more retina signs were more likely to be smokers and have higher systolic blood pressure. Over a median followup of 3.1 years, 10.1% of those with two or more signs developed functional impairment, while 7.1% of those with fewer than two signs experienced difficulty with daily activities.
Post-hoc analysis confirmed that having two or more retinal signs was associated with disability, but having only one sign had no connection. The researchers also warned that the findings could be subject to selection bias, since overall study participants without retinal photography tended to be older, black females with more vascular risk factors and diseases. The best way to use retinal photography in clinical risk prediction has yet to be determined.
|■ Eylea phase 3 trial in China. Regeneron Pharmaceuticals and Bayer HealthCare have initiated a phase 3 trial evaluating the efficacy and safety of FDA-approved Eylea in the treatment of wet AMD in China.|
The new trial, named SIGHT, will include approximately 300 patients.
“Currently, only photodynamic therapy with verteporfin is approved as a treatment for wet AMD in China, and it is only approved for the subpopulation of patients with predominantly classic wet AMD,” said kemalMalik, MD, head of Global Development for Bayer.
■ UK not likely to approve Lucentis for DME. The UK National Institute of Health and Clinical Excellence (NICE) that evaluates drugs for the treatment of various diseases and conditions said it has reached a preliminary decision not to approve Lucentis for the treatment of DME.
Carole Longson, MD, director of NICE's Health Technology Evaluation Centre, said that the independent appraisal committee recognized the effect of macular edema on patients' everyday life, but had to be sure of any drug's clinical and cost-effectiveness.
“NICE has recently recommended dexamethasone as a clinically and cost-effective treatment for this indication, but the evidence presented for Lucentis did not support a positive recommendation for this condition,” said Dr. Longson.
■ Iluvien not approved for DME. Alimera Sciences has received a complete response letter (CRL) from the FDA denying approval for the Iluvien implant for the treatment of DME associated with diabetic retinopathy. A CRL is issued by the FDA's Center for Drug Evaluation and Research when its review of an application is completed and questions remain that preclude the approval of the NDA in its current form.
The FDA stated that it was unable to approve the Iluvien NDA because the NDA did not provide sufficient data to support that Iluvien is safe and effective in the treatment of patients with DME. The FDA stated that the risks of adverse reactions shown for Iluvien in the FAME study were significant and were not offset by the benefits demonstrated by Iluvien in these clinical trials.
The FDA has indicated that Alimera will need to conduct two additional clinical trials to demonstrate that the product is safe and effective for the proposed indication. Alimera immediately requested a meeting with the FDA to discuss further steps.
■ New data on PCV drug. Oxigene, a clinical-stage biopharmaceutical company developing novel therapeutics to treat eye diseases, announced what it termed “encouraging data” from the FAVOR study of zybrestat in polypoidal choroidal vasculopathy (PCV).
FAVOR is a phase 2 study investigating the use of a single intravenous injection of Zybrestat at different doses compared to placebo in patients with PCV, followed by imaging of the retina on days 2, 8, 15 and 8. The data showed that Zybrestat was well tolerated in the study. The primary objective of the study was to observe the change in the number of polyps from baseline following administration of the drug. Although this number was essentially unchanged, there were some suggestions of efficacy, with a decrease in polyp activity and a reduction in subretinal fluid and retinal edema in patients receiving Zybrestat.
According to the presentation announcing the new data, polyps in PCV do not generally respond to anti-VEGF monotherapy. The current treatment of choice for PCV is photodynamic therapy, with the possibility of recurrence and hemorrhage after treatment.
■ MicroPulse laser therapy for DME. Iridex announced that data from a clinical study compiled over 10 years demonstrates the safety and efficacy of MicroPulse laser therapy for treating DME without the retina tissue damage associated with conventional laser therapy.
The study was led by Jeffrey K. Luttrull, MD, an ophthalmologist and retinal surgeon with the Ventura County Retina Vitreous Medical Group in California. A total of 252 eyes with macular edema (212 eyes due to diabetic retinopathy, 40 eyes due to branch retinal vein occlusion) were followed. Of these, 181 patients met study inclusion criteria, received sub-visible MicroPulse laser treatment, and were followed for up to 10 years. RP