Rx Perspective
Evaluating a New Glaucoma Drop
A researcher highlights key data to help guide your decisions on using Rescula.
COORDINATED BY PAUL N. SCHACKNOW, M.D., PH.D. 

The FDA recently approved Novartis Ophthalmics' unoprostone isopropyl (Rescula) for the treatment of ocular hypertension (OHT) and primary open-angle glaucoma (POAG).

Rescula exhibits efficacy equivalent to betaxolol (Betoptic, Betaxon, Betoptic S), a favorable safety profile and is well tolerated in patients, making it another helpful treatment choice.

KEY DATA

A look at some key data will help guide your use of Rescula in practice:

• Pharmacology. Unoprostone, which is available in a 0.15% solution and dosed twice daily, is a 22-carbon atom molecule that the FDA has labeled a docosanoid. It reduces intraocular pressure (IOP) by increasing outflow. Whether it acts primarily by conventional or uveoscleral outflow hasn't been determined. It doesn't exhibit affinity for prostaglandin receptors or any receptors traditionally associated with glaucoma therapy.
• Phase III studies. The U.S. phase III study compared the 12-hour IOP-lowering effect of unoprostone vs. timolol maleate (Timolol Maleate, Betimol, Timoptic XE) 0.5% b.i.d. in 571 patients with POAG or OHT during 6 months. Unoprostone provided a statistically significant reduction in diurnal IOP of about 14% (-3.0 mm Hg). It was less effective than timolol maleate (-4.5 mm Hg), but demonstrated a consistent mean change from baseline at each time during the 12-hour diurnal IOP.
  The phase III study in Europe compared the 12-hour diurnal IOP efficacy of unoprostone 0.15% b.i.d., timolol maleate 0.5% b.i.d., and betaxolol 0.5% b.i.d. in 556 patients with POAG or OHT over 6 months. (See chart above.) The efficacy of unoprostone (19% reduction from baseline) wasn't equivalent to timolol maleate but was equivalent to betaxolol at every time point during diurnal assessment and at each follow-up visit.

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  Adjunctive therapy. Adjunctive therapy with unoprostone 0.15% was recently evaluated vs. dorzolamide (Trusopt) 2.0% and brimonidine (Alphagan) 0.2%, each used twice daily added to timolol maleate 0.5% b.i.d. over 12 weeks in patients with POAG and OHT. Unoprostone (-2.7 mm Hg) didn't differ significantly from dorzolamide (-2.8 mm Hg) or brimonidine (-3.1 mm Hg) in decreasing IOP.
  Unoprostone 0.12% was also studied in combination with latanoprost (Xalatan) in 41 patients with POAG or OHT. Patients were initially treated with latanoprost 0.005% for 28 days. Afterward, those with an IOP >= 19 mm Hg were randomized to receive, in addition to latanoprost, either placebo or unoprostone 0.12% for 8 weeks.
  Unoprostone displayed a mild additive ocular hypotensive effect to latanoprost, which was statistically significant (-1.0 mm Hg). However, eyes (n = 14) that exhibited a baseline pressure of >= 22 mm Hg on latanoprost alone had an average mm Hg reduction, compared to baseline, of 5.1 mm Hg at trough (P = 0.001) and 3.0 mm Hg decrease in diurnal pressure
  (P = 0.001) when unoprostone was added. Cystoid macula edema (CME) and uveitis weren't noted, and unoprostone didn't worsen conjunctival hyperemia (Stewart et al.).
• Safety. No specific issues regarding systemic side effects have arisen with unoprostone. In a treadmill exercise study of healthy patients (Stewart, et al.), timolol maleate significantly decreased heart rate during exercise and recovery, while unoprostone didn't differ from placebo. A pulmonary function study of patients with mild to moderate asthma found no significant differences between unoprostone and placebo.
  In clinical trials, there were no reports of uveitis, herpes, CME, eyelash changes, or endothelial cell toxicity. In the U.S. Phase III trials, the percentage of patients reporting one or more ocular adverse events was similar for the timolol maleate and unoprostone groups, although a marginal significance was observed for stinging with unoprostone. One case of iris pigmentation was noted in the European Phase III trial.

ROLE IN THERAPY

Because unoprostone is so well tolerated, it should make an excellent early adjunctive medication, with efficacy similar to dorzolamide or brimonidine. And for patients who need mild to moderate IOP reduction, but in whom you wish to avoid the side effect profile of other medications, you can consider unoprostone for monotherapy.

Dr. Stewart is the Clinical Professor of Ophthalmology at the University of South Carolina School of Medicine and Director of Medical Affairs at Pharmaceutical Research Corporation in Charleston, S.C. He's been a principal investigator in numerous open-angle glaucoma studies.