Laird Harrison

July 16, 2015

VIENNA — For patients with neovascular age-related macular degeneration, the experimental drug RTH258 (Alcon Pharmaceutical and Novartis) is as effective as aflibercept, but the volumes required are much smaller, two phase 2 clinical trials indicate.

The results suggest that RTH258 is effective when delivered with a micropump, said Rishi Singh, MD, from Case Western Reserve University in Cleveland, Ohio.

"You would have, basically, programmed therapy through the pump delivering the microvolume infusion," he told Medscape Medical News. "At different points in time, you could alter, or tune, the therapy to the patient's needs."

RTH258 is a single-chain antibody that is smaller than other drugs for macular degeneration, such as bevacizumab and ranibizumab, Dr Singh explained. "The compound has three potential benefits over other neovascular age-related macular degeneration agents."

First, it might allow the delivery of high molar concentrations, he explained. Second, it might allow better penetration to relevant tissues, an effect already seen in animal studies. And third, it might allow sustained delivery.

Dr Singh presented results from the two trials here at the American Society of Retina Specialists (ASRS) 2015 Annual Meeting.

OSPREY Trial

In the phase 2 OSPREY trial, Dr Singh and his team compared outcomes in 44 patients treated with RTH258 6 mg and 45 patients treated with aflibercept 2 mg.

At baseline, mean best corrected visual acuity in the study cohort was 54.8 letters, and mean baseline central subfield foveal thickness was 493 μm. Of the 89 lesions, 49% were predominantly classic, 23% were minimally classic, and 28% were occult.

At 28-week follow-up, improvement in best corrected visual acuity was 5 to 7 letters in both groups.

At 44-week follow-up, the trend lines diverged: In the RTH258 group, the improvement over baseline was about 5 letters, and in the aflibercept group, the improvement over baseline was maintained or slightly improved out to week 56.

However, the improvements were statistically equivalent throughout the study, Dr Singh reported. Because of the small number of participants, the study had a low statistical power.

"It's important to remember these are phase 2 clinical trial designs," he said. "They are mainly to discuss trial design for phase 3, in which we'll eventually look at primary end points of efficacy," he pointed out.

At week 28, trend lines showed that the reduction in central subfield foveal thickness was greater in the RTH258 than in the aflibercept group, but at week 56, the reduction was similar in the two groups. Dr Singh called these effects "equal" as well.

The incidence of treatment-emergent adverse events was also similar in the two groups, he said.

However, by 56 weeks, there was a significant difference in the number of injections received by patients in the RTH258 and aflibercept groups (324 vs 372).

In the second study, a microvolume study, Dr Singh and colleagues compared outcomes in 13 patients randomly assigned to treatment with 1.2 mg of a 10-μL injection of RTH258 and 13 patients treated with an infusion of 1 mg in 8.3 μL RTH258.

Microvolume Study

For the primary end point, patients had to meet at least three of the following four criteria: a gain in best corrected visual acuity of at least four letters at day 14 or at day 28, and a decrease in central subfield foveal thickness of at least 80 μm at day 14 or at day 28.

This was met by 70% of patients in the injection group and by 60% in the infusion group.

"The microvolume study showed that we were able to deliver a small volume of infusion, which may enable sustained intravitreal delivery via a micropump," Dr Singh said.

The manufacturers are developing both the drug and the pump to go with it, he reported. The pump will be refilled with injections, but the injections will be less frequent than those used to administer drugs currently available for age-related macular degeneration.

 
We can get excited about this, but it has to translate to phase 3 results. Dr Timothy Murray
 

If successful, such an approach could pay big dividends, said session moderator Timothy Murray, MD, from Miami, Florida.

Intravitreal injections cause patients discomfort and cost society a lot of money, he told Medscape Medical News. It is encouraging to see that RTH258 reduced the number of injections needed.

"With microinjections, there may be fewer complications," he added. For example, they might not cause the temporary increase in intraocular pressure seen with the injections of the currently available drugs.

However, he cautioned that these results are preliminary: "We can get excited about this, but it has to translate to phase 3 results," he said.

Dr Singh reports that he has consulted for Alcon, Bausch + Lomb, Genentech, Regeneron, Shire, and Zeiss. Dr Murray reports that he has consulted for Alcon.

American Society of Retina Specialists (ASRS) 2015 Annual Meeting. Presented July 11, 2015.

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