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Pirenzepine showing promise in clinical trials for topical myopia treatment
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For today’s myope, the treatment options are more abundant and sophisticated than ever, including highly effective spectacles, contact lenses, refractive surgery procedures – and now a new drug.
Pirenzepine may hold the promise of reducing the progression of myopia by at least 50% in the first 12 months of therapy in children who suffer from myopia. The compound is currently in phase 2 clinical trials, and Valley Forge Pharmaceuticals Inc. has entered into a licensing agreement with Novartis Ophthalmics to market it.
“This is a very exciting era in myopia treatment,” said Donald Mutti, OD, PhD, myopia researcher and associate professor at the Ohio State University College of Optometry. “Consider all of the excitement about refractive surgery, which is really just supplying diopters in a different way. This agent actually has the potential to change the way the eye grows and to change the axial lengths you will end up with.”
How pirenzepine works
Dr. Mutti told Primary Care Optometry News that pirenzepine’s exact mechanism of action is not entirely known, but it is similar to the anti-muscarinic drug atropine. “For a long time, people thought atropine was beneficial because it paralyzed accommodation, and accommodation was thought to be something that made myopia progress more rapidly,” he said. “But, recently, animal studies have caused people to be more interested in the retinal and visual control of eye growth.”
Dr. Mutti explained that pirenzepine is a “selective anti-muscarinic,” meaning it has more of an affinity for neural muscarinic receptors than ciliary body muscarinic receptors.
“The question that is being asked in pirenzepine studies is: can we get the same beneficial effects of atropine without the child being dilated and under cycloplegia?” he said. “It is like a designer atropine, trying to get all of the goodness of atropine, without the dilation and cycloplegia.”
According to R. Michael Siatkowski, MD, who also participated in studies of the drug, the selectivity of pirenzepine is what sets it apart from other anti-muacarinic drugs.
“The difference between atropine and pirenzepine is the selectivity of the muscarinic receptors,” he said in an interview. “Atropine primarily works at the M3 with regard to the decrease in myopic progression, but has M1 and M2 activity as well. Pirenzepine has very little M3 muscarinic activity and it is much more selective for M1.”
Clinical trials
Dr. Siatkowski discussed the results of the pirenzepine clinical trial in which he was an investigator. He said the study consisted of 174 patients, with between 0.75 D and 4 D of myopia, who were randomized in 2-to-1 pirenzepine/placebo groups. The patients studied were between the ages of 8 and 12 years old, Dr. Siatkowski said. They were given pirenzepine 2% ophthalmic gel or the placebo twice daily for 1 year.
“At the end of 1 year, the amount of myopic progression in the pirenzepine group was only half that of the placebo group,” he said.
According to the study results, mean baseline refractive error was –2.10 D in the pirenzepine group and –1.93 D in the placebo group. Mean myopic progression at 12 months was –0.26 D with pirenzepine and –0.53 D with placebo. Only 2% of pirenzepine subjects had more than 1 D of myopic progression at 1 year vs. 20% of the placebo group.
In terms of adverse events, the frequency was similar between the two groups. According to the study results, treatment was generally well tolerated; however, 11% of pirenzepine subjects withdrew from the study due to adverse events vs. none of the placebo subjects. The most common adverse events were gel residue on the eyelids, blurred vision at near and asymptomatic conjunctival reactions.
“There were no serious adverse events reported at all,” Dr. Siatkowski said.
Future of pirenzepine
In terms of clinical data, practitioners report that pirenzepine is showing a great deal of promise so far.
“Pirenzepine has shown a significant treatment effect on the order of slowing the rate by half in the first year,” Dr. Mutti said. “Now our question is, will it be sustained? Is it just going to be that amount of reduction and then no difference the next year? What happens when you stop treatment? How long do kids have to use it?”
Dr. Siatkowski agreed that more studies need to be performed on pirenzepine before its exact role in myopia treatment can be established. “At this point, we can’t say for sure. We have to do the phase 3 studies,” he said. “We have to see how the drug is used over many different areas and many different age groups.”
Useful for adult myopia?
In terms of adult myopia progression, Dr. Siatkowski said this is an area that will likely be explored, but added that it has not been determined whether the drug would be effective for that population.
“If an adult’s myopia is progressing due to growth of the eyeball, then this drug could be useful to them,” Dr. Siatkowski said. “But there may be other reasons for their myopia progressing. Their cornea might change shape. This wouldn’t have an effect on that.”
Dr. Mutti said he believes pirenzepine could have a potential indication for adult myopia progression. “That certainly has potential,” he said. “If eye growth is eye growth across ages, that is a logical place to go. That is a question that needs to be asked and evaluated.”
Dr. Mutti added that it is still uncertain whether pirenzepine can be used in conjunction with contact lens wear. “Because it is a gel, it might take a little longer to dissolve and dissipate than a drop,” he said. “But I don’t see any reason why a child couldn’t take out a lens, use the gel, wait for the gel to dissolve and put the lens back on.”
He expressed optimism that pirenzepine could have promise as a first-line myopia treatment. “It is potentially a huge product, because it can be used on every myopic child,” he said, “and also on children who are identified to be at risk, before myopia occurs.”
For Your Information:
- Donald Mutti, OD, PhD, is an associate professor at Ohio State University College of Optometry. He can be reached at 338 West 10th Ave., Columbus, OH 43210-1240; (614) 247-7057; fax: (614) 247-7058. Dr. Mutti has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for the companies mentioned.
- R. Michael Siatkowski, MD, is a professor of ophthalmology at the Dean A. McGee Eye Institute in Oklahoma City. He can be reached at 608 Stanton L. Young, Oklahoma City, OK 73104-5065; (405) 271-1094; fax: (405) 271-3013. Dr. Siatkowski is a paid consultant for Valley Forge Pharmaceuticals Inc.