Krystal Biotech Announces First Patient Dosed in Phase 3 Clinical Trial of KB803 for the Treatment and Prevention of Corneal Abrasions in Patients with Dystrophic Epidermolysis Bullosa

Rhea-AI Summary

Krystal Biotech (NASDAQ: KRYS) has initiated dosing in the Phase 3 IOLITE clinical trial of KB803, evaluating its effectiveness in treating and preventing corneal abrasions in dystrophic epidermolysis bullosa (DEB) patients. The trial is designed as an intra-patient, double-blind, multicenter, placebo-controlled study with crossover design.

The study will enroll approximately 16 subjects, targeting DEB patients aged 6 months or older. Previous compassionate use of the treatment showed promising results, with one patient achieving full corneal healing at 3 months and improved visual acuity from hand motion to 20/25 at 8 months. The condition affects over 750 patients in the United States and 2,000 worldwide, with no current corrective therapies available.

The trial's primary endpoint will measure the change in average days per month with corneal abrasion symptoms while receiving KB803 versus placebo. The treatment is administered as a weekly eye drop at a concentration of 109 PFU/mL.

Positive

• Previous compassionate use showed full corneal healing and significant visual improvement
• Large addressable market with over 2,000 patients worldwide and no current corrective therapies
• Decentralized study design allowing home administration
• Strong statistical power of 90% to detect treatment effect

Negative

• Small trial size of only 16 subjects
• Requires 12-week run-in period before treatment can begin
• Limited previous data with only one compassionate use case

Insights

Biotechnology Clinical Development Expert

Krystal Biotech advances potential first-ever treatment for DEB corneal abrasions with promising early data in Phase 3 trial.

Krystal Biotech has initiated a critical Phase 3 trial for KB803, positioning the company to potentially address a significant unmet need in dystrophic epidermolysis bullosa (DEB) patients suffering from corneal abrasions. The trial design demonstrates robust statistical planning with a sample size of approximately 16 subjects providing 90% power to detect an effect size of at least 25% - notably strong for a rare disease study. The crossover design is particularly sophisticated, enabling each patient to serve as their own control, which is ideal for conditions with high inter-patient variability.

The earlier compassionate use case provides compelling preliminary evidence - a patient improved from hand motion vision to 20/25 visual acuity at 8 months, representing a dramatic functional improvement. This suggests KB803's COL7A1 gene delivery mechanism effectively enables local type VII collagen production in the corneal epithelium.

The market opportunity, while modest in absolute numbers (~750 US patients and ~2,000 worldwide), represents a concentrated patient population with no existing corrective therapies. The decentralized study design with at-home drug administration demonstrates patient-centric trial execution, likely enhancing recruitment and retention in this rare disease population.

If successful, KB803 would complement Krystal's existing DEB portfolio and reinforce their strategy of comprehensive disease management. The primary endpoint of reducing symptomatic days provides a clinically meaningful and patient-relevant outcome measure that directly addresses the burden of disease.

Intra-patient, double-blind, multicenter, placebo-controlled study with crossover design

Repeat administration under compassionate use was previously shown to be well tolerated and associated with full corneal healing by 3 months as well as significant visual acuity improvement from hand motion to 20/25 at 8 months

PITTSBURGH, June 24, 2025 (GLOBE NEWSWIRE) --  Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS) announced today that the first patient has been dosed in its Phase 3 clinical trial (“IOLITE”), an intra-patient, double-blind, multicenter, placebo-controlled study with crossover design evaluating KB803 for the treatment and prevention of corneal abrasions in dystrophic epidermolysis bullosa (DEB) patients. KB803 is designed to deliver two copies of the COL7A1 transgene to the corneal epithelium and enable local type VII collagen production in the front of the eye.

“The initiation of IOLITE is another important step for Krystal as we work tirelessly to treat DEB as comprehensively as possible,” said Suma Krishnan, President, Research & Development, Krystal Biotech, Inc. “With dramatic and durable improvements already reported for the patient treated under compassionate use, we are excited by the potential of KB803 to restore full eye function and reduce or eliminate the otherwise persistent threat of vision loss imposed by these recurring corneal abrasions.”

Over 25% of DEB patients are thought to suffer from ocular complications of the disease, including over 50% of patients with the recessive form of DEB (RDEB). The estimated number of DEB patients affected exceeds 750 in the United States and 2,000 worldwide. There are no corrective therapies available to the treatment or prevention of ocular complications associated with DEB. Current disease management is limited to supportive wound care and in some cases surgical interventions to remove scar tissue.

IOLITE Phase 3 Study

IOLITE is an intra-patient, double-blind, placebo-controlled, multicenter Phase 3 study with a crossover design to evaluate KB803, administered as an eye drop, for the treatment and prevention of corneal abrasions in DEB patients, 6 months of age or older.  Patients seeking to participate in IOLITE must first enroll in the ongoing natural history study and complete a 12-week run-in period, during which they report the number of days that they experience symptoms of corneal abrasions. Subjects meeting the inclusion criteria following the 12-week run-in are eligible to participate in the IOLITE trial.  

Approximately 16 subjects will be enrolled in the IOLITE study. The sample size was calculated based on the average symptomatic days per month and standard deviation data from subjects enrolled in the natural history study who would be otherwise eligible for IOLITE and provides 90% power to detect an effect size of at least 25%, allowing for a dropout rate up to 20%. Enrolled patients will initially receive either a single eye drop of either placebo or KB803, at a concentration of 10⁹ PFU/mL, to each eye once weekly for 12 weeks. At the conclusion of the first 12 weeks, patients will be switched from placebo to KB803, or vice versa, and continue with once weekly administration for a second 12 week period. IOLITE is designed as a decentralized study and drug administration will occur at the subject’s home by a healthcare provider.

The primary study endpoint will be the change in the average number of days per month with corneal abrasion symptoms while receiving KB803 versus placebo. Statistical significance will be analyzed via intra-patient paired measurements to account for potentially expected high inter-patient variability. Safety and secondary efficacy data, including weekly assessments of eye pain and monthly Epidermolysis Bullosa Eye Disease Index (EB-EDI) questionnaires, will be collected through to the end of the 24-week study period. More details of the IOLITE study can be found at www.clinicaltrials.gov under NCT identifier NCT07016750. 

Ongoing Natural History Study

48 DEB patients have been enrolled in the ongoing natural history study. 39 of the 48 subjects (81%) have RDEB and the remaining have the dominant form of DEB (DDEB). The average number of days per month with corneal abrasion symptoms reported by RDEB and DDEB subjects were 5.9 and 2.2 days, respectively.   

Previous Compassionate Use Case

Beremagene geperpavec-svdt (B-VEC) had previously been applied to the eye of one DEB patient under a compassionate use protocol. The clinical observations of this compassionate use case were published in the New England Journal of Medicine in February 2024. The patient presented with severe cicatrizing conjunctivitis secondary to DEB. Surgical symblepharon lysis of the patient’s right eye with pannus removal was conducted and regular B-VEC administration as an eye drop directly to the eye, at a concentration of ~10⁹ PFU/mL, were added to routine post-surgical care. Treatment was well tolerated with no drug-related adverse events noted. Full corneal healing was observed at three months, as well as significant visual acuity improvement from hand motion to 20/25 by eight months.

About KB803

KB803 is a redosable, eye drop gene therapy designed to deliver two copies of the COL7A1 transgene to the epithelial cells in a patient’s eye for the treatment and prevention of corneal abrasions in DEB patients. The goal of therapy with KB803 is to address the fundamental disease-causing mechanism at the molecular level, by providing the patient’s epithelial cells of the eye with the template to make normal type VII collagen locally. In a DEB patient treated under compassionate use with clinical observations reported the New England Journal of Medicine, regular eye drop administration was well tolerated with full corneal healing observed at three months, as well as significant visual acuity improvement from hand motion to 20/25 by eight months.

About Krystal Biotech, Inc.

Krystal Biotech, Inc. (NASDAQ: KRYS) is a fully integrated, commercial-stage, global biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEK®, the Company’s first commercial product, is the first-ever redosable gene therapy and the first genetic medicine approved by the FDA and EMA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and X (formerly Twitter).

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc., including statements about the potential of KB803 to restore full eye function and reduce or eliminate the otherwise persistent threat of vision loss imposed by recurring corneal abrasions associated with DEB; the Company’s expectations (i) that over 25% of DEB patients suffer from ocular complications, including over 50% of patients with RDEB and (ii) of the number of DEB patients suffering from ocular complications in the United States and worldwide; the Company’s IOLITE study, including the Company’s plans to enroll approximately 16 subjects; and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “likely,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including uncertainties inherent in the initiation and conduct of clinical trials, as well as regulatory review of clinical trials and applications for marketing approvals; and such other important factors as are set forth under the caption “Risk Factors” in the Company’s annual and quarterly reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release.

CONTACT
Investors and Media:                                                                                        
Stéphane Paquette, PhD
Krystal Biotech
spaquette@krystalbio.com

FAQ

What is the primary endpoint of Krystal Biotech's (KRYS) Phase 3 IOLITE trial for KB803?

The primary endpoint is the change in average number of days per month with corneal abrasion symptoms while receiving KB803 versus placebo.

How many patients will be enrolled in Krystal Biotech's (KRYS) KB803 Phase 3 trial?

The Phase 3 IOLITE trial will enroll approximately 16 subjects with dystrophic epidermolysis bullosa (DEB).

What were the results of KB803's previous compassionate use case?

The single compassionate use case showed full corneal healing at 3 months and improved visual acuity from hand motion to 20/25 by 8 months, with no drug-related adverse events.

How is KB803 administered in Krystal Biotech's Phase 3 trial?

KB803 is administered as a single eye drop to each eye once weekly at a concentration of 109 PFU/mL by a healthcare provider at the patient's home.

What is the market size for Krystal Biotech's KB803 treatment?

The treatment targets over 750 patients in the United States and 2,000 worldwide who suffer from corneal abrasions related to dystrophic epidermolysis bullosa.