NEW YORK (Reuters Health) - A new formulation of pilocarpine (Vuity, Allergan) was shown to improve presbyopia in a pivotal phase 3 trial.
The 1.25% pilocarpine solution was approved by the US Food and Drug Administration in October 2021.
It is not approved outside of the U.S, "though Allergan is exploring the potential to work with regulatory agencies worldwide to bring Vuity to patients in need," principal study author Dr. Michael Robinson of AbbVie noted in an email to Reuters Health.
The new formulation, referred to in the JAMA Ophthalmology study as AGN-190584, "is delivered with proprietary pHast technology, which allows (it) to rapidly adjust to the physiologic pH of the tear film," Dr. Robinson said. "This was studied in simulated tear film, and the clinical significance is unknown. Vuity uses the eye's own ability to reduce pupil size, which may improve near and intermediate vision while maintaining distance vision."
The multicenter, vehicle-controlled randomized, phase 3 trial, GEMINI 1, enrolled 323 adults with presbyopia. Randomization was stratified by factors including age, iris color, baseline mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA), and emmetrope status.
The mean age was 49.6; 73% were women; 90% were white; and the baseline mean mesopic DCNVA was 29.2 letters.
Participants were randomized to AGN-190584 or placebo administered bilaterally, once daily for 30 days.
On day 30, at 3 hours after administration of the intervention by research staff, 30.7% of participants receiving AGN-190584 showed improvement in 3 or more lines in mesopic DCNVA versus 8.1% of those in the vehicle group, demonstrating that the study met its primary and key secondary end points.
At hour 6, those percentages were 18.4% and 8.8%, respectively.
At hour 8, the between-group difference in three or more lines of mesopic DCNVA gains was not significant. However, prespecified outcome measures demonstrated AGN-190584 superiority to vehicle in least-squares mean mesopic DCNVA change from baseline (5.4 vs. 3.6 letters), and photopic distance-corrected intermediate visual acuity at hour 8 (3.9 vs. 2.4 letters) and hour 10 (3.5 vs. 1.7 letters).
No participants with mesopic DCNVA improvement of 3 or more lines at hour 3 had losses of more than 5 letters in mesopic, high-contrast, binocular-corrected distance visual acuity.
The onset of effect was at 15 minutes. Safety and tolerability profiles were acceptable.
The authors conclude, "AGN-190584 was safe and efficacious through 30 days, improving near and intermediate vision on day 30 for up to 10 hours after administration and supporting its use as a treatment for presbyopia."
Dr. Jennifer Rose-Nussbaumer of Stanford University in Palo Alto, coauthor of a related editorial, commented in an email to Reuters Health, "There are some concerns about the financial incentives driving the commercialization of this new formulation of pilocarpine. Pilocarpine has been around for decades for the treatment of glaucoma."
"A simple trial randomizing patients to 1% pilocarpine - the commercially available version - versus their formulation of 1.25% with new vehicle would have been the simplest design," she noted. "Stratification of the randomization on things like age and eye color just complicated the design and analysis and makes it harder to interpret the results."
"They also tested the vision in various light conditions while avoiding testing vision in very dark lighting, in which pilocarpine may worsen the vision," she noted.
"They did not provide a refraction after using the pilocarpine," she added. "Pilocarpine causes a refractive shift toward near-sightedness, so it may be that the patients were able to see better up close because they lost distance vision."
The study was funded by Allergan prior to its acquisition by AbbVie. Dr. Robinson and three coauthors are employees of AbbVie and may hold stock, and several coauthors have received fees from Allergan/AbbVie.
SOURCE: https://bit.ly/362CyxO and https://bit.ly/3t6NeEV JAMA Ophthalmology, online March 3, 2022.
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