Treating chronic pediatric conditions: pirenzepine ophthalmic gel (PIR) for the slowing of progression of pediatric myopia as a model pediatric development program

Purpose There is a growing interest in developing drugs for the treatment of pediatric diseases. Combining pediatric development with chronic use and prevention of disease progression indication(s) present special challenges to the clinical pharmacologist. Myopia is a very prevalent disease (up to 80% in some countries), for which current treatments meet only the optical pathology, not ocular comorbidity, or the underlying structural abnormality. Pirenzepine is a m 1 ‐selective muscarinic antagonist, long used orally in Europe, and effective in animal models of myopia. Methods Valley Forge developed a stable ophthalmic gel. The ocular safety and tolerance of PIR was investigated in a short‐term study with two year follow‐up in myopic children. Subsequently, multi‐year, worldwide studies were conducted on the safety and efficacy of the highest tolerated concentration. Results In an initial Phase 2 study, myopic children tolerated up to 2% PIR. In two subsequent one year Phase 2 studies, 2% PIR, b.i.d. reduced the rate of progression of myopia by ~50%. While there were some traditional m 3 ‐antagonist undesirable effects observed (e.g., mydriasis, accommodation complaints), they were for the most part not therapy limiting, and were much less than expected from a non‐selective muscarinic antagonist such as atropine. Conclusions PIR presents promise as a chronic treatment for prevention of disease progression for pediatric myopia. A continuing development program is planned. Clinical Pharmacology & Therapeutics (2004) 75 , P23–P23; doi: 10.1016/j.clpt.2003.11.086