Pooled Analysis of Data from Two Phase 3 Clinical Trials of Upneeq for Acquired Ptosis Published

RVL Pharmaceuticals, a subsidiary of Osmotica Pharmaceuticals, announced that JAMA Ophthalmology has published pooled analysis of data from two phase 3 clinical trials of Upneeq (oxymetazoline hydrochloride ophthalmic solution) 0.1% for treatment of acquired blepharoptosis (ptosis) in adults. Upneeq, a novel pharmacologic agent, is the first and only ophthalmic formulation approved by the FDA for the treatment of ptosis. Upneeq is a preservative-free eye drop administered once daily to the ptotic eye(s).  

In two phase 3 studies comprising of 304 patients, the treatment was associated with positive outcomes after instillation on days 1 and 14 and was well tolerated.  

Ptosis is an abnormal drooping of the upper eyelid margin with the eye in primary gaze.¹ In addition to the characteristic asymmetric or sleepy appearance caused by ptosis, obstruction of the pupil by the upper eyelid can lead to superior visual field deficits.² Ptosis is a common eyelid disorder that is often associated with aging.³⁴⁵

“Upneeq contains oxymetazoline, a potent, direct-acting alpha-adrenergic receptor agonist, which when administered to the eye, is believed to stimulate Müller muscle causing contraction resulting in elevation of the upper eyelid,” Tina deVries, PhD, Executive Vice President, Research & Development, Osmotica, said in a company news release. “These trials represent a meaningful step in our evolution to an innovation-focused specialty pharmaceutical company.”  

“Acquired blepharoptosis is a common, but often overlooked and under-treated, ophthalmic condition, leaving many patients frustrated until they become candidates for surgery,” Charles Slonim, MD, Chief Medical Officer, Oculos Development Services and lead medical monitor for the phase 3 trials, said in the news release. “In these clinical trials, we saw statistically significant improvements in the ptosis-induced superior visual field defects and drooping upper eyelid positions. These improvements were observed from the first patient assessment on Day 1 and maintained over the 14-day treatment period. Upneeq, which was just recently approved by the FDA, has the potential to significantly change the treatment paradigm in a condition where patients and clinicians have had only surgical treatment options.”

The pooled analysis combined data from 2 randomized, double-masked, placebo-controlled, multicenter phase 3 clinical trials (Study RVL-1201-201 and Study RVL-1201-202) totaling 304 participants including 203 receiving Upneeq and 101 receiving vehicle once daily as a single drop per eye for 42 days. Overall, 97.5% of participants receiving oxymetazoline 0.1% and 97.0% of participants receiving vehicle completed the studies.

The primary efficacy endpoint was change from baseline in the number of points seen on the Leicester Peripheral Field Test (LPFT), a test to detect superior visual field deficits due to ptosis, on days 1 (6 hours post-instillation) and 14 (2 hours post-instillation). The secondary endpoint, change from baseline in Marginal Reflex Distance 1 (MRD-1), was assessed at the same time points.

Key trial findings published in JAMA Ophthalmology include the following

• Increase from baseline in mean number of points seen on superior visual field (LPFT):
  • Day 1: 5.9 ± 6.4 (oxymetazoline 0.1%) versus 1.8 ± 4.1 (vehicle),
    • mean difference: 4.07 (95% CI: 2.74, 5.39), p<0.001
  • Day 14: 7.1 ± 5.9 (oxymetazoline 0.1%) versus 2.4 ± 5.5 (vehicle),
    • mean difference: 4.74 (95% CI: 3.43, 6.04), p<0.001

• Increase from baseline in upper eyelid elevation (MRD-1):
  • Day 1: 0.96 ± 0.89 mm (oxymetazoline, 0.1%) vs 0.50 ± 0.81 mm (vehicle),
    • mean difference: 0.47 mm (95% CI: 0.27, 0.67), p<0.001
  • Day 14: 1.16 ± 0.87 mm (oxymetazoline, 0.1%) vs 0.50 ± 0.80 mm (vehicle),
    • mean difference: 0.67 mm (95% CI: 0.46, 0.88), p<0.001

Treatment emergent adverse events (TEAEs) were observed in 31.0% of patients receiving Upneeq and 35.6% of patients receiving vehicle. Among participants receiving Upneeq and reporting a TEAE, 81% had a maximum TEAE intensity of mild. No serious TEAE was suspected of being treatment-related, and all were resolved.

There were no mean shifts from baseline in vital signs, or intraocular pressure, Snellen, visual acuity, pupil diameter, slit-lamp or ophthalmoscopy/fundus results in either eye judged to be clinical relevant.

In addition to 6-week efficacy trials, a randomized, double-masked, placebo-controlled, multicenter Phase 3 clinical trial was conducted to evaluate the safety of Upneeq over 12 weeks of once daily treatment. The results of this study will be reported separately.