Novartis’ proprietary anti-VEGF agent RTH258 (brolucizumab) appears to be noninferior to aflibercept for treatment of neovascular age-related macular degeneration (AMD), according to results from 2 ongoing phase 3 studies. The studies show the drug also appears more durable than aflibercept.
Brolucizumab is a small molecule human monoclonal antibody fragment with high affinity for all VEGF-A isoforms. With a molecular weight of only 26 kDa (compared with 48 kDa for ranibizumab and 115 kDa for aflibercept), a 6-mg dose can be delivered in a single 50-μl intravitreal injection.
The multicenter trials, HAWK and HARRIER, compared safety and efficacy of intravitreal brolucizumab (6 mg) with standard aflibercept (2 mg) in more than 1,800 wet AMD patients. The assigned treatment was administered on day 0, week 4 and week 8, then as needed per the dosing regimen until week 96. An additional study arm in HAWK also assessed a 3-mg dose of brolucizumab.
For both dose levels, the primary and secondary outcome measures—change in BCVA from baseline at week 48 and mean BVCA change during weeks 36 to 48—were met.
Furthermore, brolucizumab demonstrated impressive durability compared with aflibercept. After the initial 3 injections, patients in the brolucizumab arms received additional doses at 12-week intervals with the option to adjust to 8-week intervals based on disease activity assessments by masked graders. Aflibercept was dosed every 8 weeks according to its label. Following treatment loading, more than half of brolucizumab patients were able to maintain q12w dosing up to week 48.
The drug was well tolerated, and the rates of ocular and systemic adverse effects were similar to those in the aflibercept arms.
"These results clearly and convincingly demonstrate RTH258 has the potential to reduce injection burden while providing excellent visual outcomes,” said Vas Narasimhan, MD, global head of drug development and chief medical officer at Novartis. “Given our legacy in developing medicines to preserve vision, we are pleased that RTH258 carries the promise of being the next major advancement for patients with nAMD. Based on these robust data, we are looking forward to working with regulatory agencies to bring this pioneering treatment to patients."
The 2 studies will follow patients up to week 96, with an estimated completion date of May 2018.