番茄社区

SEATTLE -- An ocular implant containing a reformulated cancer drug preserved vision and stabilized retinal thickening for up to a year while dramatically reducing treatment burden for neovascular age-related macular degeneration (nAMD), according to a small study reported here.

Both the axitinib (Inlyta)-containing OTX-TKI implant and bimonthly aflibercept (Eylea) produced a 1- to 2-letter improvement in best-corrected visual acuity (BCVA) at 52 weeks, while mean central subfield thickness (CSFT) increased by about 20 µm with the implant versus a decrease of about 2 µm with intravitreal aflibercept, a clinically insignificant difference.

Patients who received the bioresorbable implant had an 89% reduction in treatment burden as compared with aflibercept treatment, reported Robert L. Avery, MD, of California Retina Consultants in Santa Barbara, at the American Society of Retina Specialists (ASRS) meeting.

"The study showed good safety, no signs of drug-related problems," said Avery. "The bioresorption of the implant is complete by 12 months, and due to the pharmacokinetics and pharmacodynamics, it seems like this would warrant a re-treatment in 9 to 12 months."

In response to a question, Avery said the implant is less likely to be noticeable to a patient, in comparison with a dexamethasone implant, for example.

"It goes through a 25-gauge needle instead of 23-gauge, and it's more translucent ... because of its size and not casting as much of a shadow," he said. "I would not say that no one has seen it, but I think it is a lot less likely."

A multitargeted tyrosine kinase inhibitor (TKI), axitinib has 10 times greater preclinical potency for inhibiting VEGF receptors, particularly VEGFR2, "the most pathologic of the receptors," said Avery. OTX-TKI combines the potent TKI with a bioresorbable implant made from proprietary technology developed for targeted, sustained drug delivery. The device has an estimated drug-delivery interval of 9 to 12 months.

Avery reported findings from a small randomized (3:1) trial comparing the implant to intravitreal aflibercept administered every 8 weeks. Eligible patients had already received intravitreal anti-VEGF therapy. Patients allocated to OTX-TKI received a single intravitreal dose of aflibercept 4 weeks after implantation, followed by sham injections to mimic the aflibercept control arm.

The primary outcomes were safety, changes in BCVA and CSFT, and need for supplemental anti-VEGF injections. Criteria for supplemental injections were a 10-letter loss in BCVA, a 5-letter loss plus a 75-µm increase in CSFT, or a new macular hemorrhage.

The study included a total of 21 advanced-age patients (mean ages of 76 and 84) with a mean nAMD duration of 18 months. Baseline mean BCVA was about 70 letters, and mean CSFT was 274 µm in the OTX-TKI group and 241 µm in the aflibercept group. Patients in each group had received an average of eight intravitreal injections in the previous 12 months.

At 6 months, 80% of patients in the OTX-TKI group had received no supplemental anti-VEGF injections. About three-fourths remained free of supplement injections at week 40, tailing off to about 60% to week 52 (33% inclusive of week 52).

"These were heavily treated patients, most of them receiving monthly injections," said Avery. "Afterwards, there's a dramatic 89% reduction in the treatment burden ... The median time to rescue injection was 44 weeks, so the implant was durable."

No drug-related ocular or systemic adverse events (AEs) occurred in the implant group. One patient developed endophthalmitis following the required aflibercept injection at 4 weeks, and the inflammation resolved with antibiotics. The same patient developed a mild cataract that resolved.

Avery said a planned phase II/III pivotal trial of OTX-TKI could begin before the end of the year.

In a separate report at ASRS, suprachoroidal injection of axitinib achieved a similar reduction in treatment burden while maintaining visual acuity during 6 months of follow-up, reported Rahul N. Khurana, MD, of Northern California Retina Vitreous Associates in Mountain View.

Khurana presented results from a 28-patient dose-escalation study of CLS-AX, an axitinib suspension administered by intrachoroidal injection. Eligible patients had nAMD, two or more anti-VEGF treatments in the previous 4 months, and confirmation of persistent, active disease.

Khurana focused on 14 patients treated with the three highest doses of CLS-AX. The patients had a mean age of 83, a baseline mean BCVA of 63 letters, and a mean CSFT of 208 µm. Duration of nAMD averaged 53 months, and the patients had received a cumulative total of 35 anti-VEGF injections (approximately 10 per year).

In the 6 months prior to treatment with CLS-AX, the study participants had received an average of five intravitreal injections. During the 6-month follow-up after CLS-AX administration, the mean number of injections was about one, representing reductions in treatment burden of 77% to 85% across the three dose groups. BCVA remained stable throughout the 6 months of follow-up.

"CLS-AX had an excellent safety profile at all doses," said Khurana. "There were some really exciting early signs of durability, with a nearly 80% reduction in the treatment burden. CLS-AX is now being evaluated in a phase IIb clinical trial for neovascular AMD."