Lirentelimab well-tolerated, effective for severe allergy conjunctivitis

Lirentelimab safely improved severe allergy conjunctivitis and concomitant atopic symptoms, according to a study published in The Journal of Allergy and Clinical Immunology.

Stephen D. Anesi, MD, FACS, an associate partner at Massachusetts Eye Research & Surgery Institution, and colleagues noted that ocular allergy is estimated to affect at least 20% and up to 40% of the U.S. population.

“Physicians may resort to systemic corticosteroids for patients with chronic and aggressive symptoms, but its use is associated with adverse effects, especially with long-term use,” Anesi and colleagues wrote. “There clearly remains a substantial need for a targeted treatment that can be safely used in a chronic setting for allergic conjunctivitis.”

To determine the safety and preliminary efficacy of lirentelimab (AK002, Allakos) — an anti-siglec-8 monoclonal antibody that depletes eosinophils and inhibits mast cells — the researchers conducted an open-label phase 1b study that included 30 patients, 87% of whom had atopic comorbidities.

The researchers sorted the patients into three cohorts according to their diagnosis of atopic keratoconjunctivitis (AKC; n = 13; median age, 50 years; 38% women; 85% white), vernal keratoconjunctivitis (VKC; n = 1; age, 25 years; 0% women; 100% white) or perennial allergic conjunctivitis (PAC; n = 16; median age, 55 years; 50% women; 93% white).

During the 6-month study period, 27 patients received all six monthly doses of lirentelimab. Five patients discontinued due to withdrawal of consent, physician decision or sponsor decision due to noncompliance.

The most common adverse events were mild to moderate infusion-related reactions, including flushing, feeling of warmth, headache, nausea or dizziness. The only treatment-related adverse events were such infusion-related reactions, usually after the first infusion.

Otherwise, the researchers reported that there were no drug-related serious adverse events or withdrawals related to adverse events.

Between weeks 21 and 22 — corresponding to the 2-week period after the final dose of lirentelimab — the mean change in patient-reported allergic conjunctivitis symptoms from baseline was –61% (95% CI, –75 to –48), which was consistent for the AKC group (–63%), VKC group (–87%) and PAC group (–59%).

Based on investigator analysis, ocular signs and symptoms showed improvement at the final dose timepoint (–53%; 95% CI, 76 to –31), which was maintained during all follow-up timepoints until approximately week 32, 12 weeks after the final dose. Overall, 83% of patients responded to treatment, with 17% showing complete response, based on total results for ocular signs and symptoms.

Patients with pre-existing atopic comorbidities reported a decrease in perceived severity at all posttreatment timepoints, including at assessments during weeks 21 to 22 compared with baseline for atopic dermatitis (–55%; 95% CI, –78 to –31), asthma (–50%; 95% CI, –82 to –19) and rhinitis (–63%; 95% CI, –87 to –38).

Patients also reported improved or stable quality of life compared with baseline.

“Despite the scarcity of treatment options and high prevalence of disease, there have been no innovations in therapy to relieve the burden of the disease,” Anesi and colleagues wrote. “Our study is the first ever clinical trial conducted of a biologic targeting allergic conjunctivitis and we demonstrated preliminary efficacy in reducing the symptoms of patients with moderate to severe AKC, VKC and PAC.”