Oral tyrosine kinase inhibitor shows promising early results in AMD patients

Oral pazopanib was well tolerated and may have improved visual acuity and central retinal lesion thickness in patients with neovascular age-related macular degeneration, according to a small study.

Perspective from Carl D. Regillo, MD

The analysis comprised data from two studies: a 14-day phase 1 placebo-controlled study with 72 healthy subjects and a 28-day phase 2a open-label study with 15 patients who had subfoveal choroidal neovascularization secondary to AMD.

The AMD patients received oral pazopanib 15-mg tablets once daily for 28 days. Healthy subjects received single or repeated oral pazopanib 5-, 10-, 20- or 30-mg tablets or placebo once daily for 14 days.

Patients were examined at baseline and weekly during treatment.

Administration of a 15-mg dose for 28 days yielded a mean eight-letter gain in best corrected visual acuity, a reduction in central retinal thickness of 50.28 µm and a reduction in central retinal lesion thickness of 50.94 µm in nine AMD patients who did not undergo rescue therapy.

Six AMD patients received intravitreal injection of anti-VEGF agents; all six patients had the high-risk CFH Y402H CC genotype for AMD.

Mild to moderate ocular adverse events were reported by seven of 15 patients in the AMD group. The most common non-ocular adverse events were intermittent headache in two patients and upper respiratory tract infection in two patients.

Pazopanib was well tolerated in the healthy subjects and patients with AMD.

Disclosure: See the study for a full list of all authors’ relevant financial disclosures.

Perspective

Carl D. Regillo, MD

McLaughlin and colleagues report on a small phase 2 study to treat wet AMD with an oral VEGF inhibitor (pazopanib) that works by blocking tyrosine kinase of VEGF and placental growth factor receptors. An oral medicine dosed once daily is an attractive alternative to current state-of-the art with the burden of frequent, office-based, physician-administered anti-VEGF intravitreal injections. The good news is that the dose-escalating phase of the study in healthy volunteers showed that the drug was well tolerated, even at the highest dose tested. Unfortunately, the drug did not have a treatment effect that was comparable in magnitude to anti-VEGF intravitreal injection therapy in improving visual acuity or reducing central retinal thickness at the end of the 28-day study period in the 15 patient cohort with new-onset wet AMD. Therefore, it is unlikely that this drug will be tested or ultimately approved as initial monotherapy for wet AMD. However, there was some encouraging benefit in the subgroup with low-risk CFH genotype. This leaves the door open for this drug to be used potentially as an adjunct in the maintenance phase of anti-VEGF therapy to reduce the frequency of injections or possibly even stop injections in patients with wet AMD who have this specific genetic profile.

Carl D. Regillo, MD

OSN Retina/Vitreous Board Member

Disclosures: Regillo receives research support and consulting fees from Genentech, Regeneron and GSK.

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Source: JAMA Ophthalmol. 2013;doi:10.1001/jamaophthalmol.2013.5002.