Pegpleranib Promising as Macular Degeneration Pretreatment

Laird Harrison

September 19, 2015

NICE, France — In patients with treatment-resistant neovascular age-related macular degeneration, pretreatment with pegpleranib (Fovista, Ophthotech) might increase the effectiveness of anti-vascular endothelial growth-factor (VEGF) therapy, a preliminary study indicates.

"The numbers are very small," said Pravin Dugel, MD, from the University of Southern California in Los Angeles. "It's not definitive, but the fact that the results are consistent with the biology is encouraging," he told Medscape Medical News.

Dr Dugel presented the findings here at the European Society of Retina Specialists 15th EURETINA Congress.

Although anti-VEGF treatments have proven effective for most patients, the large number of injections required makes the therapy tiring and expensive. And some patients still gain no benefit.

Researchers analyzing the mechanisms that limit the effectiveness of anti-VEGF drugs have found that pericytes confer resistance to anti-VEGF blockade in new blood vessels, and anti-VEGF treatment increases pericyte coverage of these vessels, said Dr Dugel.

They have also found that platelet-derived growth factor (PDGF) recruits pericytes and plays a role in fibrosis and angiogenesis, he explained.

In phase 2 trials, combination therapy with anti-VEGF treatment and pegpleranib, which blocks PDGF, reduced the amount of fibrosis and improved visual acuity. Large randomized controlled trials are currently underway.

As part of a pilot for a large 2-year antifibrosis study, Dr Dugel and his colleagues assessed 30 patients treated with a combination of pegpleranib plus aflibercept or bevacizumab. Ten of these patients were also pretreated with pegpleranib.

Average age of the study participants was 80 years, and 16 were women. At baseline, visual acuity was 55 ETDRS letters.

Participants had received a mean of 25 previous anti-VEGF treatments, 89% of which were less than 6 weeks apart. Three of the patients had never been treated before, and the 27 who had been experienced recurrent fluid or no improvement in visual acuity despite treatment.

"It's a really difficult group of patients," Dr Dugel reported. "When you see improvement in these patients, it's a big deal."

Table. Increases in Visual Acuity

Patient Group Letters at 3 Months Letters at 7 Months Gain of ≥10 Letters, %
Treatment history      
   Naïve 17.66
   Resistant 7.07 8.88
Pegpleranib status      
   Pretreatment 11.10 16.50 70
   No pretreatment 4.70 4.41 18


Pegpleranib appeared to be effective whether it was paired with bevacizumab or aflibercept, Dr Dugel said.

This seems to be "a very promising development in two ways," said Anat Loewenstein, MD, from Tel Aviv University in Israel.

"One is that it may carry better visual acuity results and a longer duration of the therapy," she told Medscape Medical News. "But the more exciting thing is that fact that it may prevent fibrosis, which we're not able to prevent with other therapies."

Dr Dugel reports financial relationships with many ophthalmologic product companies and stock ownership in Alimera, Macusight, Ophthotech, and Digisight. Dr Loewenstein has disclosed no relevant financial relationships.

European Society of Retina Specialists 15th EURETINA Congress. Presented September 17, 2015.


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