Study finds QPI-1007 safe for patients in range of doses

Salt Lake City-One intravitreal injection of QPI-1007 (Quark Pharmaceuticals) to treat nonarteritic anterior ischemic optic neuropathy (NAION) was safe with no serious adverse events in a phase I trial.

In additon, most patients gained 3 or more lines of vision, according to Bradley Katz, MD, PhD, who reported the results on behalf of the Quark Study Group.

The primary endpoint of the multicenter, international, phase I, open-label, dose escalation trial of QPI-1007 was the drug’s safety, whereas the secondary endpoint was the visual outcome, explained Dr. Katz, associate professor, John A. Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City.

The study target was caspase 2, which is a unique protein, Dr. Katz said, because it has features of both an initiator and an effector of apoptosis, and it is activated in rat models of ischemic optic nerve injury.

QPI-1007 is a custom-designed, small-interfering RNA that binds to the messenger RNA of caspase 2 and prevents the messenger RNA from being translated into a protein, he continued.

The study had 2 strata: one included patients who were blind in one eye as a result of a retinal or optic nerve problem, and the other included patients with acute NAION. The doses studied were 0.2, 0.6, 1.2, 2.4, 4.8, and 6 mg, and three blind patients were injected with each of the doses (n = 18 patients). With the increasing doses-when no adverse events occurred-the patients with NAION were then treated. Ten patients with NAION received the 1.2-, 2.4-, or 6.0-mg dose (n = 30 patients).

Dr. Katz reported that the study was completed and there were no serious adverse events or dose-limiting toxicities. The adverse events that occurred were mild and the usual side effects associated with intravitreal injections, including conjunctival hemorrhage (48%), conjunctival edema (19%), ocular irritation (17%), and ocular pain (17%).

Regarding visual outcomes, Dr. Katz reported that at month 3, 51.7% of the study cohort gained 3 lines of vision compared with 39.7% in the Ischemic Optic Neuropathy Decompression Trial (IONDT). At the 6-month evaluation, the respective data were 44.8% and 42.6%. At 12 months, 28.6% and 41.2% of patients maintained the 3-line gain in vision.

Dr. Katz noted an interesting finding at 3 months: In the IONDT, 9.1% of that cohort lost at least 3 lines of vision, whereas no patient in the phase I trial lost 3 lines or more of vision. At the 6-month evaluation, 14.8% of patients in the IONDT lost 3 lines or more of vision compared with none in the phase 1 study, and at 12 months, 15.8% of IONDT participants lost 3 lines or more of vision compared with 3.6% in the phase 1 study.

“One intravitreal injection of QPI-1007 was well tolerated,” he said. “The most striking result was that only one patient lost 3 or more lines of vision at month 12, which merits further investigation. In contrast, 15% to 20% of patients in the IONDT lost 3 or more lines of vision at 6 months.”

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