Long-Awaited Treatment for Demodex Blepharitis Receives FDA Approval

A recent announcement provides a groundbreaking treatment for patients with Demodex blepharitis. The FDA approval of lotilaner ophthalmic solution 0.25% (Xdemvy, Tarsus Pharmaceuticals; Figure),¹ formerly referred to as TP-03 during clinical trials, is the first-ever prescription option for Demodex blepharitis, marking a significant milestone in ocular surface disease and providing a much-needed alternative to traditional OTC options.

CLINICAL TRIALS

FDA approval of lotilaner was granted after successful completion of the randomized, multicenter, double-masked, vehicle-controlled Saturn-1 and Saturn-2 clinical trials.^2,3 These studies demonstrated the safety and efficacy of lotilaner in 833 participants, 415 of whom received lotilaner ophthalmic solution. Patients with Demodex blepharitis randomly received lotilaner or vehicle at a 1:1 ratio and dosed twice daily in each eye over the course of 6 weeks.

The primary endpoint of the trials was the reduction of eyelash collarettes; the secondary endpoints included mite eradication and eyelid erythema reduction. Both trials showed statistically significant improvement in collarette reduction, mite eradication, and eyelid erythema alleviation compared with the control vehicle. The trials also established a favorable safety profile, with the drops being well-tolerated by most patients.^2,3

The most common side effects reported, occurring in 10% of patients, were burning or stinging sensations. A small percentage (< 2%) of patients developed chalazion/hordeolum and punctate keratitis.

TREATMENT, WARNINGS, CONTRAINDICATIONS

Lotilaner is a 6-week treatment course, administered as two drops per day in the affected eye. Patients should store the bottle at room temperature, and the drug should not be instilled while wearing contact lenses, as it may cause lens discoloration.

There are no known contraindications for the use of lotilaner. Although the treatment has not been specifically studied in pregnant women or during breastfeeding, based on available data, the risks to a developing fetus or infant appear to be low. In animal reproduction studies, lotilaner did not produce malformations at clinically relevant doses, and systemic exposure is believed to be minimal in humans.

It’s worth mentioning that the safety and effectiveness of lotilaner in pediatric patients under the age of 18 years have not been established. However, children are not the primary demographic of interest because Demodex prevalence increases with age.^2,3

CLINICAL DIAGNOSIS AND MANAGEMENT

For optometrists and ophthalmologists who treat dry eye disease or ocular surface disease, Demodex blepharitis is one of the more challenging anterior segment conditions to manage, primarily due to the limited treatment options available. Although the clinical sign of collarettes at the base of the eyelashes has made Demodex blepharitis easily identifiable for decades,⁴ effectively eradicating the mites through traditional therapies has proven to be painstakingly difficult.

Roughly 58% of adult patients visiting eye care providers show evidence of Demodex infestation,⁵ leading to symptoms such as irritation, itchiness, dryness, fluctuating vision, eyelid redness, and contact lens intolerance.⁶

Eye care providers primarily rely on lid hygiene-based treatments, such as tea tree oil eyelid wipes or scrubs, for managing Demodex blepharitis. However, these treatments do not directly address mite infestations, and their effectiveness remains uncertain.⁷ Treatments for mite eradication include procedures such as BlephEx (BlephEx) or Zocular Eyelid System Treatment (ZEST; Zocular), and an intense pulsed light has also been used for its miticidal properties. However, these procedures have historically been out-of-pocket expenses for patients, while eyelid hygiene products are only available OTC. Consequently, patients have been left with treatment options not covered by insurance, limiting procedural options to those who could afford them.

Lotilaner represents a significant advancement, as it is the first Demodex blepharitis treatment that may fall under medical insurance coverage, providing a more accessible and potentially more effective option for patients.

MECHANISM OF ACTION

Lotilaner is an antiparasitic drug and has been as a veterinary medication to treat fleas and ticks in dogs and cats.⁸ Belonging to the isoxazoline family of compounds, it causes paralysis and eventual death to parasites through the inhibition of gamma-aminobutyric acid-gated chloride channels.⁹ Due to its high lipophilicity, lotilaner is efficiently absorbed, making its way into eyelash follicles through sebum and meibomian glands, precisely where Demodex mites reside.¹⁰

NEW HORIZONS

This landmark treatment marks the first FDA-approved option for the estimated 25 million individuals in the United States who may have Demodex blepharitis.^11,12 Lotilaner is a prescription option that may be covered by insurance, alleviating financial burden on patients. It also offers patients an alternative to costly, out-of-pocket procedures and reduces their sole reliance on OTC lid hygiene products. The newly approved drug is expected to be available by prescription by the end of August.