Ocuseva, a drug in clinical trial in Japan for treatment of Retinitis Pigmentosa

R-Tech Ueno Ltd. (Tokyo, Japan) announced it has completed a phase 2 clinical trial of 0.15% UF-021 isopropyl unoprostone (Ocuseva), which is under development as a treatment for retinitis pigmentosa (RP). The trial investigated the possibility of improving visual function in the central part of the retina with UF-021 in patients with RP.

The randomized, multicenter, comparative study examined 112 patients with RP that had progressed to the mid-to late-stage, defined as a visual acuity of less than 6/18 with a narrow visual field. Patients received placebo or Ocuseva, instilled one drop per time or two drops per time (at a 5 minute interval), twice a day in the morning and evening for 24 weeks. The primary efficacy endpoint was the change seen on the visual field analysis as checked by an instrument called the MP-1 microperimeter (Nidek, Gamagori, Japan), Retinal sensitivity was also studies by a regular Humphrey visual field analyzer (10-2), visual acuity, contrast sensitivity, and health-related quality of life, using a questionnaire on visual function (VFQ-25).

After 24 weeks, positive change in the retinal sensitivity of the central 2 degree field of vision from baseline increased the most in the two-drops-per-time group, followed by the one drop- per-time group. The placebo group had the least significant increase in sensitivity.

The change in the retinal sensitivity from the pretreatment level by 4 dB or more was seen as improvement in 15.2% of patients in the placebo group, 7.9% in the one-drop-per-time group, and 18.4% in the two-drops-per-time group, whereas the change was seen as aggravation in 21.2% in the placebo group, 15.8% in the one-drop-per-time group, and 2.6% in the two-drops-per-time group. There were a significantly lower number of aggravated cases in the 2-drops-per-time group, compared with the placebo group. The retinal sensitivity measured with the Humphrey perimeter showed statistically significant improvement at weeks 4 and 8 in the two-drops-per-time group compared with the placebo group.

The main adverse effect of Ocuseva was ocular irritation, which, the company said, disappears several minutes after instillation.

The results show promise, specifically with the advantage that it only requires instillation of drops, rather than a completed surgical intervention. Ocular irritation, which anyway lasts a few minutes, is the only adverse effect. The follow-up in the trial is 6 months (24 weeks), which is considered good enough to consider in any retinal trial. The only thing difficult to understand is the group that was instilled with placebo drops (meaning no medication) still showed improvement in about 17 of the 112 patients in the trial (15.2%).