Osmotica’s Upneeq provides an alternative to surgery.

Droopy upper eyelids don’t get the same kind of cosmetic attention as, say, balding pates, sagging cheeks or droopy jowls. Still, they affect almost 12% of the U.S. population over age 50 says Osmotica, citing a 1995 study by Sridharan et al. And, until recently, surgery was the only effective treatment for the condition.

But in July of this year, the FDA gave aging eyelids a lift when it bestowed its blessing on Osmotica to begin marketing Upneeq (oxymetazoline hydrochloride ophthalmic solution), 0.1%, as the only nonsurgical, drop-based remedy for acquired blepharoptosis (ptosis, for short), the technical term for abnormal drooping of the upper eyelids.

John P. Fezza, MD, for one, welcomes the new drug.

“A substantial number of patients have eyelid ptosis, and up to this point, the only way to fix it was really surgery,” says Dr. Fezza, an oculoplastic surgeon at the Center for Sight in Venice, Fla., who was involved in the clinical trials leading to FDA approval.

“Ptosis is often overlooked or under-diagnosed,” agrees Jason Bacharach, MD, an eye surgeon at North Bay Eye Associates in California, who was also involved in the clinical studies. The delicacy involved in addressing the patient’s appearance means that “many times, the condition is not addressed unless a patient initiates the conversation,” he explains.

There are several types of ptosis, which causes partial or complete dysfunction of the Müller’s and the levator superioris muscles that elevate the eyelid. Upneeq is targeted at the most common type: acquired, or age-related, ptosis. Severity ranges from mild cases that simply betray a person’s age, to cases severe enough to cover the pupil and limit field of vision.

“It can … make tasks such as driving challenging and potentially dangerous,” says Dr. Bacharach.

STRONG PERFORMANCE IN CLINICAL STUDIES

According to Osmotica, Upneeq demonstrated statistically significant improvements compared to placebo in superior visual field, as measured by the Leicester Peripheral Field Test (LPFT), and eyelid lift, as measured by the Marginal Reflex Distance Test (MRD-1) in two pivotal double-masked efficacy studies. A third pivotal safety study involving 140 patients showed that Upneeq was well tolerated when administered once daily in the morning (to both eyes) over a 12-week period. The majority of adverse events were mild and self-limited.

The prevalence of ptosis is estimated at about 11.5% of U.S. adult patients over the age of 50. That corresponds to “an estimated 13 million patients,” says Dr. Bacharach, citing the 1995 Sridharan study.

MECHANISM OF ACTION AND ADVERSE EFFECTS

Upneeq works similarly to phenylephrine, a dilating drop that is also used to selectively target Müller’s muscle and elevate the eyelid to see if surgical ptosis repair will work, according to the company. “The downside is that phenylephrine dilates the pupil pretty significantly,” says Dr. Fezza.

Upneeq’s adverse effects are comparatively less serious. According to the drug’s prescribing information, adverse reactions occurring in 1% to 5% of study subjects were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, eye irritation and headache.

As an alpha-adrenergic agonist, Upneeq should be used with caution in patients taking beta-blockers, antihypertensives and/or cardioglycosides, as well as andrenergic receptor antagonists and monoamine oxidase inhibitors.

ADVANTAGES OVER SURGICAL PTOSIS REPAIR

Drs. Fezza and Bacharach say Upneeq avoids the risks of surgery, which can include the risk of anesthesia, loss of vision, bleeding, infection, dry eye and need for further surgery due to asymmetry or over- or under-elevated upper eyelid.

Dr. Fezza relates that surgical ptosis repair of an upper eyelid can be challenging to achieve perfect results, as it is truly an “art form melded with science.”

“There’s always a risk that you can raise a lid too high, or not do it enough, or you could have asymmetry, and you have to go back and revise,” he says. With Upneeq, “the revision rate goes to nothing with the drop.”

Even some patients who aren’t concerned about the procedure’s risks either can’t have surgery or may not want to go under the knife, explains Dr. Bacharach. “Many patients may prefer a non-surgical alternative even if they are not high-risk for a procedure. This may be particularly true for someone with milder ptosis,” he says.

It’s worth noting that Upneeq doesn’t take surgery off the table. Patients may choose to start with Upneeq and then at some point decide to pursue the more permanent surgical option.

“This is where educating doctors and patients is key, so everyone, both as clinicians treating the disease and patients with the conditions, can have an informed conversation regarding options,” says Dr. Bacharach.

Dr. Fezza reported in the clinical trial that Upneeq was effective in temporarily elevating a droopy upper eyelid caused by aged-related changes, and this was “aesthetically very pleasing.”

He also did not detect any rebound irritation or redness during clinical studies. “When you use some other eye-whitening drops, you can get rebound redness from blood vessels dilating. I didn’t witness that with Upneeq.”

FEAR NOT, EYELID SURGERY BUSINESS

“Is this going to cannibalize eyelid surgery? I don’t think so,” Dr. Fezza says. “I think this is going to be synergistic.” Both he and Dr. Bacharach believe the drug could drive more people to the practice, much as Botox has improved patient flow into the eyebrow lift business.

Upneeq will provide an alternative to surgery, particularly for those patients who cannot have or do not want surgery. It may also provide a way for the patient to trial a higher upper lid prior to surgery, Dr. Fezza explains.

“No pun intended, but this is an uplifting treatment option,” Dr. Bacharach adds. “The nearly instantaneous satisfaction that patients and doctors will see post-dosing will put a smile on everyone’s face.” OM