Dompe Initiates Global Phase 3 Trial of DFL24498, a Novel Dual-Mechanism Treatment for Atopic Keratoconjunctivitis
Global Phase 3 Trial of Novel Dual-Inhibitor DFL24498 Commences
Dompe Farmaceutici S.p.A., an Italian pharmaceutical company specializing in innovative ophthalmic solutions, has begun enrolling patients in a global Phase 3 trial (NCT07395232) of DFL24498, a treatment for Atopic Keratoconjunctivitis (AKC). This trial will involve 138 adult patients in a multi-center, randomized, double-blind, vehicle-controlled study, evaluating the efficacy and safety of the drug over a 12-week period. The primary endpoint is the change in Visual Analog Scale (VAS) scores for ocular itching at week 6, aiming to demonstrate the drug's ability to rapidly improve symptoms.
Unique Dual Mechanism Targeting Both Mast Cells and T Cells
DFL24498 possesses a unique dual mechanism of action, simultaneously inhibiting TRPML2, an activator of mast cells involved in innate immunity, and calcineurin, a key regulator of adaptive immunity. Unlike existing allergic ophthalmic treatments that primarily focus on either T-cell inhibition or antihistamine effects, this drug offers the potential to block both early hypersensitivity reactions and chronic inflammatory responses. This innovative mechanism is expected to provide a powerful treatment option for patients with severe AKC who have not responded adequately to existing single-therapy approaches.
High Unmet Need in Severe Ophthalmic Disease Causing Corneal Damage
Atopic Keratoconjunctivitis is characterized by chronic and recurrent inflammation of the ocular surface, unlike simple allergic conjunctivitis. If left untreated, it can lead to corneal ulcers and vision loss, making it a serious rare ophthalmic disease. The global allergic conjunctivitis market is currently valued at approximately USD 2 billion to 4.3 billion in 2024 and is expected to continue to grow. However, treatment options for severe patients are limited. The emergence of a highly effective and safe non-steroidal treatment that can replace topical corticosteroids, which can cause side effects such as glaucoma and cataracts with long-term use, would have significant commercial value in the market.
Strong Pipeline Driven by Prior Oxervate Approval
Dompe, a privately held company, previously achieved a significant milestone by obtaining the world's first FDA approval for Oxervate (cenegermin) in 2018 for the treatment of neurotrophic keratitis, demonstrating its unique development and commercialization capabilities in the field of rare ophthalmic diseases. The initiation of the Phase 3 trial for DFL24498, which incorporates this accumulated expertise, can be seen as a strategic move to further strengthen the company's ophthalmic portfolio. The trial, which began in December 2025, is expected to be completed by March 2027, with top-line results anticipated within the next two years, paving the way for a more defined commercialization roadmap.
The initiation of the Phase 3 trial for DFL24498 represents a key milestone in the approximately USD 2 billion to 4.3 billion global ophthalmic allergy market, as it explores the potential of a dual-mechanism (TRPML2+calcineurin) drug that offers advantages over existing single-mechanism calcineurin inhibitors such as tacrolimus. If the Phase 3 trial, involving 138 patients, demonstrates significant relief of itching (improvement in VAS scores) as a replacement for topical steroid treatments, it will further enhance the value of Dompe's pipeline. From a researcher's perspective, demonstrating the mechanistic superiority of a combined mechanism that simultaneously inhibits mast cells and T cells in controlling severe chronic ocular surface inflammation could establish a new treatment standard in the ophthalmic field. Given Dompe's track record of successfully obtaining the first approval for Oxervate, the success of this Phase 3 trial will be a critical turning point in determining the potential for future global partnerships and licensing agreements.
Source: ClinicalTrials.gov (api_ct)