BLOG: AGN-190584 demonstrates impressive safety, efficacy results
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AGN-190584 met the FDA’s high bar for safety and efficacy endpoints in the phase 3 GEMINI study.
The FDA requested the results be distance corrected for refractive error with a large percentage of patients achieving a three line or more improvement in mesopic conditions. Importantly, it also requested that the treatment demonstrate a minimal impact on distance visual acuity — no more than five letters lost by hour 3 of day 30.
AGN-190584 (pilocarpine 1.25%, Allergan) met both primary and key secondary efficacy endpoints; no patients lost distance vision, and the treatment showed a rapid onset of action within 15 minutes and sustained vision gains up to 6 hours. These data along with the GEMINI 2 study formed the basis of the new drug application currently under FDA review; we expect action by year’s end.
Patient-reported outcomes showed that AGN-190584 participations had clinically meaningful and statistically significant greater improvement in ability and satisfaction related to near-vision reading and a reduction in the use of presbyopia-coping mechanisms during the previous 7 days of the trial vs. vehicle.
Detailed study results
GEMINI 1 evaluated 323 participants who received the drop bilaterally, once daily, for 30 days. The treated group gained three lines or more in mesopic, high-contrast, binocular distance corrected near visual acuity (DCNVA) at day 30, hour 3 (22.5%, P < .0001) and hour 6 (9.7%, P = .0114) vs. vehicle.
Additional endpoints showed that 75% of AGN-190584-treated participants achieved a two line or greater improvement in mesopic DCNVA and that 93% of participants achieved 20/40 or greater vision in photopic DCNVA. Improvements in distance corrected intermediate visual acuity were observed for up to 10 hours at day 30.
There were no treatment-emergent serious adverse events in the AGN-190584 group. The most common treatment-emergent nonserious adverse event with the study drug, occurring in more than 5% of participants, was headache. Most side effects were mild and transient, with only 1.2% of participants discontinuing treatment.
Real-world implications, benefits
Not only were no distance vision letters lost, but numerical gains in distance vision were actually observed. This is likely due to the mechanism of small-aperture optics and resulting improvement in overall depth of focus. This finding further increases our confidence in the real-world benefits of AGN-190584.
Our patients are looking for a solution that is easy, safe and well tolerated, with good durability. This drop checked all of those boxes. The impressive findings exceeded our expectations. The statistically significant improvement in intermediate vision — critically important with the use of computers, smartphones and tablets — was seen at all time points, out to 10 hours.
We found AGN-190584 safe and well tolerated with extremely low rates of discontinuation. Participants were rigorously questioned about headache, before and after instillation. No participants assigned to the active treatment discontinued the drops; the only severe headache reported was in the vehicle group.
If approved, this formulation of pilocarpine 1.25% with its proprietary vehicle will be the first and only eye drop specifically designed to treat presbyopia — a huge win for our patients. The SAS technology allows for rapid equilibration of pilocarpine, improving tolerability by adjusting to a natural pH and increasing bioavailability.
AGN-190584 may be a “gateway drug” for the public’s understanding of presbyopia, and I expect an enormous response from our patients if it is approved.
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