Oral drug shows promise in nAMD treatment. Photo: NEI.

Successful as anti-VEGF therapy has been, the intravitreal injection drug delivery method is fraught with risks and obligations. Though the pharma industry has tried to develop oral options for neovascular AMD in the past, only to fail, a new one known as AKST4290 (Alkahest) was reported to be well-tolerated and associated with improved visual acuity, according to a phase 2a clinical study. AKST4290 is a highly specific and potent small-molecule human C-C chemokine receptor type 3 (CCR3) antagonist. The researchers noted in their paper, published in Retina, that an oral route may lessen the current treatment burden posed by anti-VEGF injections.

The prospective, multicenter study included 30 patients with newly diagnosed, treatment-naïve neovascular AMD. The participants self-administered 400mg of the drug orally twice a day for six weeks. The researchers reported a mean BCVA gain of seven letters, with 83% of patients achieving stable or improved vision and 21% of patients gaining ≥15 letters. None of the patients experienced any severe or serious adverse events.

“Inhibition of CCR3-mediated [cell] migration [through Bruch’s membrane] and protection against further degradation of the RPE may have an important impact on active disease progression,” the researchers explained in their paper. “Blocking the CCR3 receptor may also reduce immune cell recruitment and inflammation, regulate cytokines, improve vascular perfusion and interrupt endothelial cell migration, thereby reducing the morphological changes attributed to pathologic choroidal neovascularization.”

Larger placebo-controlled trials with longer duration are scheduled to evaluate this drug candidate.