Ocular Surgery News: Treatment of DME poses complex choices, strives to overcome limitations

Dr. Pravin U. Dugel – Ocular Surgery News U.S. Edition, June 25, 2018

Ocular Surgey News

Unmet needs and new options

There are unmet needs for DME, mainly related to the high rate of poor responders and the burden of frequent injections.

“There are still patients that have suboptimal improvement, so better efficacy is still an unmet need. Durability is definitely an issue. Anti-VEGF therapy works very well on average, but it takes long-term treatment and frequent administration. We want a treatment that lasts longer and works better and faster. We want to prevent recurrences, too,” Regillo said.

Current options have inherent limitations and are not entirely sustainable, according to Pravin U. Dugel, MD, who is an OSN Retina/Vitreous and OSLI Retina Board Member.

“Very few patients can bear the burden of being treated every month for years and years, so sustainability is a big problem. The other big problem are those patients, approximately 50%, who initially are poor responders and go through several attempts of continuing, changing or combining therapies because we don’t know what may work,” he said.

However, research is moving fast, and there are many exciting new potential treatments in the pipeline, including a new generation of anti-VEGF drugs, the most prominent of which is brolucizumab (RTH258, Novartis). It is a single-strand antibody fragment, the first of its kind, with a much greater concentration than any of the existing anti-VEGFs and therefore potentially greater efficacy and durability.

“Brolucizumab has met its primary endpoint in neovascular AMD, and I am sure that it will be studied in DME and DR as well,” Dugel said.

“The other one is abicipar pegol (DARPin, Allergan), which according to the manufacturers could potentially offer dosing every 3 months. Again, studies on DME have not started yet but will most likely be the next step, depending on the results of AMD,” he said.

Among combination drugs, RG7716 from Genentech/Roche seems to be the most promising, according to Dugel.

“It is a bispecific drug, combining anti-vascular endothelial growth factor A (anti-VEGF-A) and anti-angiopoietin-2 (anti-Ang-2). Results are very encouraging,” he said.

Nesvacumab, an Ang-2 antibody co-developed in combination with aflibercept by Regeneron and Bayer, showed a biological signal, but not large enough to move into phase 3 testing. Another interesting new option awaiting results is OPT-302 (Opthea), a VEGF-C and VEGF-D inhibitor used in combination with anti-VEGF-A.