This first-in-human study of RTH258 demonstrated noninferiority in the change in CSFT at 1 month for the 4.5- and 6.0-mg doses compared with ranibizumab and an increase of 30 days in the median time to PBT for the 6.0-mg dose. There were no unexpected safety concerns, and the results support the continued development of RTH258 for the treatment of neovascular AMD.
Background
Despite the success of anti-vascular endothelial growth factors (anti-VEGF), there is currently a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD).
Purpose
To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment designed specifically for intraocular use in humans.
Methods
In this article, we summarize the pre-clinical and current clinical evidence for brolucizumab, with an outlook to other treatment regimens and additional indications under investigation.
Results
The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dosing in one intra-vitreal injection compared with other anti-VEGF agents. The Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal Phase III trials HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control.
Conclusions
The pre-clinical and clinical data for brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.
These data suggest that internal resection of high posterior melanomas may conserve ocular and functional vision and does not seem to increase the risk of metastatic disease. Longer follow-up is necessary to establish the safety of the procedure.
Our results suggest that intraoperative application of platelet concentrate in combination with vitrectomy may be useful in managing posttraumatic full-thickness macular holes, thus improving anatomic and visual outcomes. The greater recovery of visual acuity obtained in this study compared with that obtained in other series of idiopathic macular holes could be related to the young age of the patients with traumatic macular holes and the early diagnosis and treatment.
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