Quoin Receives FDA Clearance for Second Netherton Trial

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Today, Quoin Pharmaceuticals announced it received FDA clearance to begin a second pivotal clinical trial for its investigational therapy QRX003, targeting Netherton Syndrome (NS). This development marks another significant milestone for Quoin as it advances its therapeutic candidate through late-stage clinical evaluation.¹

Background

NS is a severe, autosomal recessive genetic skin disorder caused by mutations in the SPINK5 gene. This results in a deficiency of LEKTI, a serine protease inhibitor, leading to unregulated kallikrein activity and subsequent skin barrier dysfunction, excessive desquamation, chronic inflammation, and debilitating pruritus.

QRX003 is a topical lotion containing a broad-spectrum serine protease inhibitor. Designed to inhibit the kallikrein proteases implicated in NS pathology, QRX003 aims to restore skin barrier integrity and mitigate key symptoms. In earlier clinical data, QRX003 demonstrated encouraging therapeutic activity, including rapid and sustained skin healing, resolution of pruritus, and elimination of night-time sleep disturbances.

Study Methods

The newly cleared pivotal study, CL-QRX003-002, will enroll approximately 12 to 15 subjects, each applying QRX003 twice daily to at least 80% of their body surface area (BSA). This builds upon a prior open-label study in which treatment was confined to around 20% of BSA, typically the arms and legs. The increased application area in CL-QRX003-002 is expected to yield a more comprehensive safety and efficacy profile reflective of real-world usage.

Participants in this study will continue their existing off-label systemic therapies alongside QRX003, enabling researchers to assess QRX003 as an adjunctive treatment. This trial runs in parallel with Quoin’s monotherapy trial, CL-QRX003-003, led by Amy Paller, MD, at Northwestern University, where subjects receive QRX003 alone, without any concurrent systemic therapy.

Together, both pivotal trials are expected to recruit 24 to 30 subjects across 6 US and up to 6 international sites. Recruitment is progressing, with 5 US sites currently open and the sixth expected to initiate by June 2025. International sites are in advanced preparation stages. Quoin aims to complete enrollment by the end of Q1 2026, positioning the company to file a New Drug Application (NDA) later that year.

Previous Data

In support of the ongoing clinical program, Quoin recently shared new data from its open-label study that further validate the therapeutic potential of QRX003. The data follow a 12-week treatment period and a subsequent 4-week discontinuation phase in the first subject enrolled.²

Clinical improvements observed during treatment were substantial. At the end of 12 weeks, the subject's Modified Ichthyosis Area of Severity Index (M-IASI) score improved from 18 at baseline to 3, and Worst Itch Numeric Rating Scale (WINRS) dropped from 7 to 2. The Investigator’s Global Assessment (IGA) also improved from “moderate” to “almost clear.” However, four weeks after treatment discontinuation, all clinical endpoints returned to baseline levels, indicating complete loss of therapeutic benefit. For example, the M-IASI score reverted to 18, and IGA returned to “moderate.”

These findings suggest that QRX003’s clinical benefits are closely tied to consistent, ongoing application. The rapid reversal upon discontinuation highlights the chronic nature of NS and the potential necessity of sustained treatment to maintain efficacy.

Strategic Implications and Outlook

With 4 ongoing clinical studies under its umbrella—3 of which are conducted under an open Investigational New Drug (IND) application with the FDA—Quoin is assembling a broad clinical data package. This approach aims to support QRX003’s registration as the first FDA-approved treatment for Netherton Syndrome.

Quoin’s CEO, Michael Myers, PhD, noted, “These data provide the clearest clinical evidence to date that the active ingredient in QRX003 is a competitive broad-spectrum serine protease inhibitor. The rapid reversal of benefit upon discontinuation highlights the critical need for chronic whole-body treatment. We remain committed to completing development expeditiously to make QRX003 widely available to the Netherton community upon approval.”

As Quoin advances its pivotal trials and gathers additional long-term safety and efficacy data, QRX003 continues to emerge as a potentially transformative treatment for a condition with significant unmet medical need.

References

1. Quoin Pharmaceuticals announces FDA clearance to initiate second pivotal whole body QRX003 Netherton Syndrome clinical study. News release. Global Newswire. Published May 22, 2025. Accessed May 22, 2025. https://www.globenewswire.com/news-release/2025/05/22/3086490/0/en/Quoin-Pharmaceuticals-Announces-FDA-Clearance-to-Initiate-Second-Pivotal-Whole-Body-QRX003-Netherton-Syndrome-Clinical-Study.html
2. Quoin Pharmaceuticals announces further clinical evidence of QRX003 effectiveness in Netherton Syndrome. News release. Quoin Pharmaceuticals. Published January 23, 2024. Accessed May 22, 2025. https://investors.quoinpharma.com/news-releases/news-release-details/quoin-pharmaceuticals-announces-further-clinical-evidence-qrx003