Topical Application of ASN008, a Permanently-charged Sodium Channel Blocker, Shows Robust Efficacy, a Rapid Onset and Long Duration of Action in a Mouse Model of Pruritus

3区 · 医学

Article

作者: Mieda, Tsutomu ; Yaksh, Tony L ; Malkmus, Shelle ; Gupta, Sandeep ; Ramachandran, Roshni ; Lin, Jun-Hsiang ; Thompson, Scott K

The sensation of pruritus, or itch, is associated with a variety of skin and medical disorders. Itch is transmitted through afferent C-fibers, and sodium channels play a key role in the transmission process. Local anesthetics, which block sodium channels, are used topically to treat itch but generally have a short duration of action and are not selective for afferent nerves underlying the itch sensation. Accordingly, there is a substantial unmet need for safe, efficacious, long-acting treatments for chronic pruritus, including nonhistaminergic itch. We investigated the dose-response, time to onset, and duration of action of ASN008 topical gel, which targets small afferent sodium channels, in a murine model of pruritus in which scratching behavior is induced by intradermal injection of chloroquine into the nape of the neck of C57BL/6 mice. Topical application of ASN008 gel resulted in a concentration-dependent reduction of scratching behavior. Onset of action was ≤1 hour, and duration of scratching inhibition was 15-24 hours. In a further study involving once-daily application for 5 days with chloroquine challenge on day 5, treatment with ASN008 gel again resulted in a concentration-dependent reduction of chloroquine-induced scratching, even when the gel was removed 3 hours after each daily application. In conclusion, topical ASN008 gel produces a dose-dependent reduction of scratching in a mouse model of pruritus, with a rapid onset and long duration of action, and may prove to be an effective, once-daily treatment of a variety of pruritic conditions in humans, including nonhistaminergic itch. SIGNIFICANCE STATEMENT: ASN008 gel produces a dose-dependent reduction of scratching in a mouse model of pruritus, with a rapid onset and long duration of action, and may prove to be an effective, once- or twice-daily treatment for a variety of pruritic conditions in humans. ASN008 gel has demonstrated good safety and tolerability in healthy volunteers and is currently under investigation in a phase 1b clinical study to evaluate safety, tolerability, pharmacokinetics, and preliminary antipruritic efficacy in atopic dermatitis patients (ClinicalTrials.gov ID: NCT03798561).

项与 ASN008(Shanghai Auson Pharmaceuticals) 相关的新闻（医药）

2023-05-23

·PRNewswire

TrialSpark Announces First Patient Dosed in Phase 2 Clinical Trial for ASN008-201 in Atopic Dermatitis

NEW YORK, May 23, 2023 /PRNewswire/ -- TrialSpark, Inc. announced today that the first patient has been dosed in its Phase 2 clinical trial for ASN008-201, a topical sodium channel blocker in development for pruritus associated with atopic dermatitis (AD). This clinical trial is a randomized, double-blind, vehicle-controlled, Phase 2 trial to evaluate the anti-pruritic efficacy, safety, tolerability, and pharmacokinetics of ASN008 in adults with mild to moderate AD (NCT05870865). Topline data for this trial is expected in 2024. Atopic dermatitis is a chronic inflammatory skin disease, and pruritus is the most burdensome and prevalent symptom in patients suffering from AD. Treating atopic itch, which impacts more than 16.5 million patients in the US, has historically been a challenge due to an incomplete understanding of the multiple mechanisms underlying its pathogenesis. "We are thrilled to have dosed our first patient in this clinical trial," said Gavin Corcoran, Chief Development Officer at TrialSpark. "Dermatology is a core focus area for our company, and there is enormous unmet patient need, so we're looking forward to progressing this clinical trial as efficiently as possible." This clinical trial will enroll approximately 120 participants at around 28 study sites across the United States. Eligible participants will be randomized in a 1:1:1:1 ratio to receive ASN008 gel 1.25%, ASN008 gel 2.5%, ASN008 gel 5%, or matching vehicle twice a day for 4 weeks (28 days), followed by a 4-week (28-day) follow-up period. "We are grateful to the patients who are participating in this clinical trial and to the healthcare professionals who are working with us to advance our research," said Benjamine Liu, TrialSpark CEO and Co-Founder. "Our company's mission is to bring new treatments to patients faster than ever before, and the contributions of patients, doctors, and sites are essential to achieving that goal." For more information about the clinical trial, please visit . About TrialSpark Founded in 2016, TrialSpark is a tech-driven pharma company differentiated by radically more efficient drug development. TrialSpark has built a technology platform that optimizes all aspects of clinical drug development, enabling more efficient trial design, faster trial completion, and higher quality trial data. The company acquires clinical-stage drugs from pharmaceutical and biotech companies and develops them faster, unlocking greater value per program and accelerating access to new treatments for patients. TrialSpark's current therapeutic areas of focus include rheumatology, dermatology, and cardiometabolic diseases. TrialSpark is actively growing its development pipeline. In November 2022, the company announced the formation of Libertas Bio following the acquisition of a majority position in a portfolio of immunodermatology assets from Asana BioSciences. The Libertas Bio pipeline includes ASN008, as well as global rights to gusacitinib, an oral Phase 3-ready dual JAK/SYK inhibitor in development for chronic hand eczema. TrialSpark also announced the formation of Highline Bio following the acquisition of worldwide rights to sprifermin - a potential first-in-class disease modifying treatment for osteoarthritis - from Merck KGaA, Darmstadt, Germany. Media Contact: [email protected] BD/Partnerships Contact: [email protected] SOURCE TrialSpark

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