XDEMVY is the first and only treatment that targets the parasites that cause the disease.
The patient, a woman in her 30s, visited Brandon Ayres, MD, seeking help for yet another flare-up of blepharitis. Despite years of symptomatic treatment with warm compresses, lid scrubs, ointments, steroids, ocular anti-inflammatories, even tea tree oil, the condition simply would not go away.
“Lo and behold, all I had to do was say, ‘Look down,’ and it was clear as day,” recalls Dr. Ayres, a corneal and anterior segment specialist at Wills Eye Hospital in Philadelphia. “Her eyelids were loaded with collarettes,” the telltale sign of the Demodex mite, a microscopically tiny and often-overlooked cause of blepharitis that is immune to conventional treatment.
Dr. Ayres immediately put the patient on XDEMVY (lotilaner ophthalmic solution) 0.25%, a new drug that directly targets the mite, and within days the inflammation began to subside. Though the patient had been on XDEMVY for only a couple of weeks, “when I saw her on follow-up, she was feeling much better,” Dr. Ayres says.
CLINICAL TRIAL RESULTS
Developed by Tarsus Pharmaceuticals, in July 2023 XDEMVY became the first and only FDA-approved treatment to directly target the Demodex mite, the root cause of Demodex blepharitis. In two randomized, multicenter, double-masked, vehicle-controlled studies (Saturn-1 and Saturn-2), 833 participants were administered either XDEMVY or vehicle at a 1:1 ratio and dosed twice daily in each eye over the course of 6 weeks.
The 415 patients who received XDEMVY demonstrated significant reduction of collarettes, the pathognomonic sign of the disease, to no more than two collarettes per upper lid in each study by Day 43, according to the company. In addition, the endpoints of mite eradication (0 mites per lash) and erythema cure (Grade 0) showed statistically significant improvement at Day 43 across both studies.
The most common ocular adverse reactions observed in the studies were instillation site stinging, reported in 10% of patients, according to Tarsus.
DO LOOK DOWN
Tarsus notes two studies have shown that Demodex blepharitis is the most common type of the condition, with an estimated prevalence of 25 million patients in the United States, or 58% of eye-care patients overall.1,2 However, it often goes overlooked because its symptoms overlap with those of other common ocular surface diseases, says Christopher Starr, MD, associate professor of ophthalmology, director of refractive surgery, ophthalmic education and the Cornea Fellowship Program at Weill Cornell Medicine, New York Presbyterian Hospital.
“Itching is a common symptom of allergic conjunctivitis and dry eye disease, but it is also common with Demodex blepharitis,” Dr. Starr says.
Another reason the disease can go overlooked is that ophthalmologists and optometrists focus mostly on the eye itself, not the eyelashes, during examinations. But even when they do look at the eyelids, the collarettes can easily be missed.
“While screening for Demodex blepharitis doesn’t require any special equipment, it does require an extra step of asking a patient to look down during a slit lamp exam,” Dr. Starr says. “When the patient looks down, we can more effectively see collarettes — waxy, crusty build-up along the lash margin. They are easy to miss if the patient doesn’t look down while at the slit lamp.”
BEYOND MANAGING SYMPTOMS
Identifying an effective treatment for Demodex blepharitis has proven elusive. Most cases are treated with warm compresses, targeted lid scrubs and steroids, ocular anti-inflammatories and tea tree oil. But these treatments have their limits.
“The majority of existing treatments can help with symptom relief and mechanically reducing collarette loads temporarily, but none have been particularly effective at eradicating the mites themselves,” explains Dr. Starr.
XDEMVY is used one drop per eye, twice a day, ~12 hours apart, for 6 weeks. And while it has yet to be proven curative, it also is not intended to be a maintenance medication, says Dr. Ayres.
“This kind of lid margin disease may recur over an extended period. But I still think patients would be receptive to using the treatment every year or two for 6 weeks. It’s still a much better [solution] than these other treatments we have.”
The development of XDEMVY resulted from a growing body of evidence that the same Demodex mites cause mange in animals, says Bobak Azamian, MD, PhD, chief executive officer and chairman of Tarsus.
“In our dogs and cats, we don’t see mange anymore. That’s because the medications we give for flea and tick control also have a profound effect on eradicating Demodex mites,”
Dr. Azamian explains. From there, he says, the company’s scientists theorized that the lipophilic molecule in lotilaner could be “perfectly suited” for blepharitis treatment.
“That allowed us to [develop an eyedrop] that would be effective at the lid margin,” he says, noting that Demodex mites hide in the oily meibomian glands as well as at the base of eyelash follicles, leading to Demodex blepharitis.
ABOUT INSURANCE COVERAGE
As the first and only FDA-approved therapeutic for Demodex blepharitis, XDEMVY can be challenging for patients to get covered by insurance providers. Elizabeth Yeu, MD, assistant professor at Eastern Virginia Medical School and president of ASCRS, says some payers require patients to fail treatment with ivermectin before they will cover the cost of treatment with XDEMVY.
Dr. Yeu notes that only limited studies with low samples sizes have been performed on the therapeutic off-label effects of oral ivermectin in Demodex blepharitis, of which the efficacy rates vastly range from being ineffective to a more moderate reduction of mites.3-5
“Eye-care professionals do not routinely write for oral anti-parasitic medications, and this is very prohibitive to the quality of patient care, especially when an approved safe and effective topical treatment for Demodex blepharitis, like XDEMVY, does exist to serve as a new standard of care with a first and best-in-class topical therapeutic option,” Dr. Yeu says.
According to Adrienne Kemp, a Tarsus spokesperson, XDEMVY is available by prescription via four nationwide pharmacies — AllianceRx Walgreens Pharmacy, Carepoint Pharmacy, BlinkRx and CVS Specialty Pharmacy. Once written, the pharmacy will reach out to the patient to confirm the prescription, assist with any financial support and offer free home delivery and/or any local pharmacy pick up option.
\In the majority of cases, patients will pay less than $100 out of pocket, with most paying as little as $50, according to Ms. Kemp. Patients and eye-care practices can obtain additional information on prescribing and patient access through Tarsus Connect: 1-866-846-3092. OM
Disclosures: Drs. Ayres, Starr and Yeu are consultants to Tarsus Pharmaceuticals.
References
1. Trattler W, Karpecki P, Rapoport Y, et al. The prevalence of Demodex blepharitis in US eye care clinic patients as determined by collarettes: a pathognomonic sign. Clin Ophthalmol. 2022;16:1153-1164.
2. O’Dell L, Dierker DS, Devries DK, et al. Psychosocial impact of Demodex blepharitis. Clin Ophthalmol. 2022;16:2979-2987.
3. Hirsch-Hoffmann S, Kaufmann C, Banninger PB, et al. Treatment options for Demodex blepharitis: Patient choice and efficacy. Klin Monbl Augenheilkd. 2015; 232: 384-387. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1545780. Accessed Jan. 26, 2024.
4. Filho PAN, Hazarbassanov RM, Grisolia ABD, et al. The efficacy of oral ivermectin for the treatment of chronic blepharitis in patients tested positive for Demodex spp. British Journal of Ophthalmology. 2011;95:893-895.
5. Holzchuh FG, Hida RY, Moscovici BK, et al. Clinical Treatment of Ocular Demodex folliculorum by Systemic Ivermectin. Am J Ophthalmol. 2011 Jun;151:1030-1034.
