NEW ANTI-VEGF AGENT

Frank G Holz, MD

The results of two phase II trials of brolucizumab (RTH258, Alcon Laboratories), a novel anti-vascular endothelial growth factor (anti-VEGF) agent, showed that the drug was safe and effective for the treatment of neovascular age-related macular degeneration (AMD), Frank G Holz MD told delegates attending the 15th EURETINA Congress in Nice, France.

“The two trials clearly showed that brolucizumab has the potential to improve visual outcomes and increase duration of action for the treatment of neovascular AMD. The drug was well tolerated and raised no safety concerns,” said Dr Holz.

While there has been tremendous progress in the treatment of neovascular AMD in recent years, there remain unmet needs in daily clinical practice, said Dr Holz. “We have made huge strides in treating macular disease but now we would also like to reduce the burden of care that frequent anti-VEGF injections place on the patient, the physician and the health system as a whole,” he said.

Brolucizumab is a single-chain antibody fragment that is significantly smaller than other anti-VEGF agents. The molecular weight of brolucizumab is 26kDa compared with 50kDa for ranibizumab and 149kDa for bevacizumab.

ACTIVE DRUG MOLECULES

“This small size allows a 22 times greater molar concentration than ranibizumab, which may allow for more active drug molecules per volume injected and faster and better penetration into relevant ocular tissues. It should also mean longer duration at the target tissue and make it more amenable to future drug delivery devices, with faster systemic clearance than current anti-VEGF compounds,” Dr Holz said.

The SEE phase I/II trial tested ascending doses of brolucizumab in 194 patients at 51 sites worldwide compared to ranibizumab. The results showed reduction in central subfield thickness at 4.5 and 6.0mg concentrations that were non-inferior to ranibizumab 0.5mg. There
were also numerically greater mean gains in best corrected visual acuity for brolucizumab 6.0mg compared to ranibizumab 0.5mg.

A second trial, OSPREY, found that vision gains with brolucizumab were non-inferior to aflibercept, with rapid and sustained reductions in central subfield thickness, said Dr Holz. In a second phase of the OSPREY trial, half of brolucizumab patients were successfully maintained with Q12 dosing, which holds promise for longer injection intervals with this drug. Phase III studies of brolucizumab in larger population groups are currently ongoing.

Frank G Holz: Frank.Holz@ukb.uni-bonn.de