Krystal Biotech Begins EMERALD-1 Trial for Neurotrophic Keratitis

Krystal Biotech has announced the dosing of the first patient in its EMERALD-1 phase 1/2 clinical trial, evaluating KB801, a redosable gene therapy eye drop for the treatment of neurotrophic keratitis (NK). This corneal disease is characterized by damage to or loss of sensory nerve function in the eye, leading to persistent corneal epithelial defects, ulcers, and even perforation.

Addressing a Rare but Increasingly Diagnosed Eye Condition

Although considered rare, with an estimated prevalence ranging between 10 to 50 cases per 100,000, neurotrophic keratitis is seeing a marked increase in diagnosis. In the United States alone, approximately 68,000 patients filed an NK-related claim in 2024, representing a 115% increase from 31,000 cases in 2020, according to company data.

Trial Design and Objectives

The EMERALD-1 trial (NCT06999733) is a double-masked, multicenter, placebo-controlled study designed to evaluate the safety, tolerability, and preliminary efficacy of KB801. A total of up to 27 adults with stage 2 or stage 3 NK, as defined by the Mackie classification, will be enrolled.

Participants are randomized in a 2:1 ratio to receive either KB801 at a concentration of 10¹⁰ PFU/mL or placebo (vehicle), administered topically to the affected eye twice weekly for 8 weeks. Patients will return for follow-up visits 2 and 12 weeks after treatment completion to monitor safety and assess the durability of corneal healing.

The primary objective of the study is to assess the safety and tolerability of KB801 in patients with neurotrophic keratitis.

The secondary objective is to evaluate efficacy, defined by the proportion of patients achieving complete durable healing of the corneal epithelium. Complete healing is defined as 0 mm of corneal fluorescein staining in the lesion area at both week 8 and week 10, as assessed by a masked reader.

A New Approach to Front-of-Eye Gene Therapy

KB801 is designed to provide localized, sustained expression of nerve growth factor (NGF) by corneal epithelial cells, addressing one of the key limitations of current treatments. Existing recombinant NGF eye drops, though effective, must be administered up to six times daily due to rapid clearance from the eye’s surface.

In contrast, KB801’s gene therapy approach may allow for less frequent dosing while maintaining consistent NGF levels, potentially reducing patient burden and improving outcomes.

“Until now, rapid protein clearance and high cell turnover in the front of the eye have severely limited the therapeutic potential of biologics and gene therapies,” said Suma Krishnan, President of R&D at Krystal Biotech. “We now have an opportunity to drive sustained expression and repeat administration of therapeutic biologic payloads with a simple eye drop application and look forward to delivering meaningful benefit to NK patients in need.”