SUBSPECIALTY NEWS

Ophthotech’s Fovista Combats Subretinal Fibrosis

Combination therapy proves effective in clinical trial.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ In an independent subgroup analysis of 70 patients in a phase 2b trial, Ophthotech (New York, NY) reported that a combination of its Fovista anti-PDGF molecule and Lucentis was more effective than Lucentis monotherapy in stopping the development and progression of subretinal fibrosis.

On a severity scale of 0 to 4, with 0 the least severe, the mean change in severity of subretinal fibrosis from baseline to the conclusion of the study at 24 weeks was 0.97 vs 2.0 (P=.003), favoring the Fovista combination therapy group. At 24 weeks, approximately twice the number of patients on standard of care anti-VEGF monotherapy (54%) were noted to have progression of subretinal fibrosis compared to the Fovista combination group (27%). In eyes without any subretinal fibrosis at baseline, subretinal fibrosis developed in 10% of patients receiving Fovista combination therapy compared to 51% in the monotherapy Lucentis group.

In related news, Ophthotech Corporation has achieved a $50 million enrollment milestone payment from Novartis Pharma AG as part of the ex-US licensing and commercialization agreement between the two companies focused on the treatment of wet AMD. This enrollment milestone payment was triggered as a result of Ophthotech reaching the first enrollment goal under the agreement in its pivotal, multinational Fovista phase 3 clinical program and is the first of a total of $130 million in potential enrollment-based milestones under the agreement.

Under the agreement signed in May 2014, Ophthotech granted Novartis exclusive rights to commercialize Fovista in markets outside the United States, with Ophthotech retaining sole rights to commercialize Fovista in the United States. Potential payments to Ophthotech under the agreement could total over $1 billion in upfront and milestone payments, not including future royalties on ex-US Fovista sales.

Early Treatment of DME Limits Need for Anti-VEGF

Some patients go a year or more without retreatment.

■ Twenty-five percent of the 500 patients who elected to participate in an Open Label Extension study that followed Genentech’s RIDE and RISE trials for Lucentis (ranibizumab) required no further PRN treatment for DME in a follow-up period that ran an average of 14 months, and more than 2 years in some patients.

The follow-up study, led by Carl Regillo, MD, of Wills Eye Hospital, in cooperation with Genentech (South San Francisco, CA), concludes that early diagnosis, prompt treatment, less advanced disease and positive overall response during the 36-month RISE and RIDE studies were the keys to a reduced need for ongoing retreatment. The study was presented at the recent Retina Society meeting in Philadelphia.

While the study found that the mean number of PRN retreatments per patient in the extension study was 3.8 per year, or less than one retreatment every three months, the 25% who needed no PRN retreatment was a key finding.

In answering the question “Who Are the 25%,” Dr. Regillo described a profile of patients who had shorter duration of diabetes (by approximately 2 years) and diabetic macular edema (by approximately 8 months) compared to patients requiring frequent retreatment. These patients also tended to enter the RISE and RIDE studies with better BCVA and with thinner central foveal thickness (CFT). Overall, these patients experienced the most meaningful improvement during the RISE and RIDE studies and entered the extension study with thinner CFT than the patients who needed a large number (seven or more) PRN retreatments during the average 14.1 month follow-up period.

“For the 25% of patients in RISE and RIDE who did not require any injections during the PRN extension phase, therapy appears to have been initiated early, with shorter duration disease, higher visual acuity, less advanced DR, and less macular edema at baseline,” Dr. Regillo concluded. “With early diagnosis and treatment, a meaningful proportion of patients with DME may be able to stabilize disease and maintain vision gains without the need for ongoing intravitreal injections.”

Seven Researchers Share Prestigious Award

They pioneered the development of antiangiogenic therapy.

■ The one-million euro Antonio Champalimaud Vision Award for 2014 will be shared by seven researchers — sometimes working independently and sometimes in groups — who over two decades led in developing antiangiogenic therapy as a successful treatment for retinal diseases. Their discoveries led to the successful use of anti-VEGF drugs that have restored sight to millions of patients around the world with retinal disease.

The researchers, who received their awards at a ceremony in Lisbon, Portugal, in September, include Joan Whitten Miller, MD, Evangelos S. Gragoudas, MD, and Patricia A. D’Amore, PhD, MBA, of Massachusetts Eye and Ear; Lloyd Paul Aiello, MD, PhD., of Mass. Eye and Ear and Joslin Diabetes Center; George L. King, MD, of Joslin Diabetes Center; Anthony P. Adamis, MD, global head of ophthalmology, immunology and infectious diseases for Genentech, who is also affiliated with HMS Ophthalmology and Mass. Eye and Ear, and Napoleone Ferrara, MD, of the University of California, San Diego School of Medicine and formerly a Genentech scientist.

Champalimaud Award recipients are selected by a distinguished international panel that includes two Nobel Laureates. The award is often referred to as the “Nobel Prize for Vision” and with its one-million ($1.3 million) purse, it is among the world’s largest scientific and humanitarian prizes.

Beginning in the 1990s, the seven researchers worked either independently or in collaboration to identify VEGF as the major cause of such common retinal diseases as wet AMD, DME, diabetic retinopathy, and retinal vein occlusion. The researchers then demonstrated that blocking VEGF with regular intravitreal injections of anti-VEGF agents could eliminate or reduce the unwanted blood vessels that led to vision loss. The researchers’ groundbreaking work led to a new class of ophthalmic anti-VEGF drugs, which first became available in the United States in 2004. These drugs include Macugen (pegaptanib sodium, Eyetech), Lucentis, and Eylea (aflibercept, Regeneron Pharmaceuticals). RP

Anthony P. Adamis, MD, (left) and Napoleone Ferrara, MD (right)

AREDS Formulations Increase AMD Risk for Some

People with certain genotypes should not take them.

■ DNA samples from 989 individuals who participated in the Age-Related Eye Disease Study (AREDS) indicate that people with a specific genotype should not be taking the AREDS formulation because it increases their risk of progression to the advanced form of AMD. The findings were recently presented in the September issue of Ophthalmology.

Carl Awh, MD, of Tennessee Retina Physicians, and colleagues evaluated DNA samples that had been collected from the AREDS trial. Overall, the AREDS trial showed a modest overall benefit of nutritional supplements for patients with AMD and became the model for most over-the-counter ocular supplement formulations. In this new study, the researchers analyzed four groups of patients, classified by their complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genetic risk.

The analysis found that for patients with high CFH and low ARMS2 risk, or 13% of the study participants, the risk of progression to advanced AMD within seven years was 43.2% for those treated with zinc, 40.2% for those treated with the AREDS supplement, and 17% for those receiving placebo.

“Patients in this genotype group had worse outcomes when treated with zinc or the AREDS formulation than with placebo,” asserted Dr. Awh. “AMD patients with two high-risk CFH alleles and no ARMS2 risk alleles — 13.1% of patients in our study — should not take the AREDS formulation.”

Dr. Awh contrasted this group against patients with low CFH and high ARMS2 risk, a group that made up 35% of study participants. For this larger group, the risk of progression to AMD within seven years was 37% lower for those taking the AREDS supplement than for those in this group who took the placebo.

“The AREDS supplements are quite helpful for patients in this group, which is the largest of the four genotype groups,” said Dr. Awh. “We think that the beneficial response of this genotype group, balanced by the poor response of patients with high CFH and no ARMS2 risk, are the basis for the overall modest benefit demonstrated in AREDS. Our analysis supports the use of genetic testing for patients before recommending an AREDS-type supplement.” RP