gusacitinib (ASN002) / Asana BioSci, Formation Bio, Sanofi - LARVOL DELTA

Libertas Bio, a Formation Bio subsidiary, License of Gusacitinib, a Dual JAK/SYK Inhibitor, to Sanofi (PRNewswire) - "Formation Bio...announced that its subsidiary Libertas Bio has licensed gusacitinib, an oral dual JAK/SYK inhibitor, to Sanofi. Sanofi will explore its potential in a new indication not previously studied through a phase 1 study. Gusacitinib was acquired by Formation Bio (formerly known as TrialSpark) in late 2022 from Asana BioSciences as part of a broader portfolio of investigational medicines. This transaction with Sanofi ushers gusacitinib into its next stage of development, with Sanofi leveraging its global expertise in drug development and commercialization to explore its potential in new indications....Deal could be worth up to €545 million, including upfront and milestone payments, as well as low to mid-teen royalties based on future sales."

Licensing / partnership • New indication • Systemic Lupus Erythematosus

A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Terminated ➔ Withdrawn

Trial withdrawal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Completed ➔ Terminated; Drug company discontinuing study.

Trial termination • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus (clinicaltrials.gov) - P1 | N=1 | Completed | Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Recruiting ➔ Completed | N=60 ➔ 1 | Trial completion date: Oct 2028 ➔ Jan 2025 | Trial primary completion date: Dec 2027 ➔ Jan 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Review of Existing and New Treatments for the Management of Hand Eczema. (PubMed, J Cutan Med Surg) - "These included studies for dupilumab, ruxolitinib, delgocitinib (LEO124249), gusacitinib (ASN002), AFX 5931, and roflumilast (ARQ-252). Two major classes of drugs emerging for the treatment of hand eczema include IL-4/IL-13 inhibitors and JAK inhibitors. With the increase in efficacy seen with these new drugs, we are also noting improved adverse effect profiles, making them attractive options to add to a clinician's management toolbox for patients with hand eczema."

Journal • Review • Atopic Dermatitis • Contact Dermatitis • Dermatitis • Dermatology • Immunology • IL13 • IL4

[[Translated article]]Janus Kinase Inhibitors in Atopic Dermatitis: New Perspectives. (PubMed, Actas Dermosifiliogr) - "We review a number of JAK inhibitors that have been recently approved for use in atopic dermatitis, such as baricitinib, upadacitinib, and abrocitinib, as well as others that are currently in the pipeline or under development, such as gusacitinib, delgocitinib, ruxolitinib, brepocitinib, tofacitinib, and cerdulatinib. The use of JAK inhibitors to block the signaling of numerous cytokines with a critical role in the pathogenesis of atopic dermatitis has revolutionized the treatment of this pathogenically complex, phenotypically heterogeneous skin disease."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Updated Review on Treatment of Atopic Dermatitis. (PubMed, J Investig Allergol Clin Immunol) - "We begin with topical treatments such as corticosteroids and calcineurin inhibitors and subsequently address the latest systemic treatments, such as Janus kinase inhibitors (upadacitinib, baricitinib, abrocitinib, gusacitinib) and interleukin (IL) inhibitors, which have proven efficacious in AD, namely, dupilumab (IL-4 and IL-13), tralokinumab (IL-13), lebrikizumab (IL-13), and nemolizumab (IL-31). Given the large number of drugs available, we summarize the pivotal clinical trials for each drug, evaluate recent real-world experience in terms of safety and efficacy for purposes of compilation, and provide evidence to guide the optimal choice of therapy."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL13 • IL4

Oral SYK/JAK Inhibitor Gusacitinib for the Treatment of Chronic Hand Eczema: Results of a Randomized Phase 2 Study. (PubMed, J Am Acad Dermatol) - "Gusacitinib showed rapid improvement in CHE patients and was well tolerated warranting further investigations."

Journal • P2 data • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immunology • Infectious Disease • Pain • Respiratory Diseases • SYK

Janus Kinase Inhibitors in Atopic Dermatitis: New Perspectives. (PubMed, Actas Dermosifiliogr) - "We review a number of JAK inhibitors that have been recently approved for use in atopic dermatitis, such as baricitinib, upadacitinib, and abrocitinib, as well as others that are currently in the pipeline or under development, such as gusacitinib, delgocitinib, ruxolitinib, brepocitinib, tofacitinib, and cerdulatinib. The use of JAK inhibitors to block the signaling of numerous cytokines with a critical role in the pathogenesis of atopic dermatitis has revolutionized the treatment of this pathogenically complex, phenotypically heterogeneous skin disease."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Topical and systemic JAK inhibitors in hand eczema - a narrative review. (PubMed, Expert Rev Clin Immunol) - "Treatment targeting specific immune pathways enables precise management and extends range of potential therapeutic options. Despite early promising results, future studies need to evaluate JAK inhibitors safety, potential risks and benefits resulting from the treatment, as well as impact of the therapy on patients QoL."

Journal • Review • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation

Clinical activity, safety and tolerability of ASN002, a dual SYK/JAK inhibitor, in patients non-Hodgkin lymphoma (NHL) and solid tumors. (ASCO 2017) - P1/2; "Pre-clinical studies indicate that ASN002 has low nM IC50s against SYK and JAK, decreases proliferation in ibrutinib-resistant cell lines, and suppresses tumor growth in rodent xenograft models of NHL and other hematologic malignancies. ASN002 was safe and well tolerated. Encouraging preliminary evidence of efficacy in NHL patients was observed. MTD has not been reached and dose escalation continues."

Biosimilar • Diffuse Large B Cell Lymphoma • Immunology • Indolent Lymphoma • Leukemia • Peripheral T-cell Lymphoma

Current emerging and investigational drugs for the treatment of chronic hand eczema. (PubMed, Expert Opin Investig Drugs) - ": Immunomodulatory drugs such as topical and systemic JAK inhibitors and Th2-targeting antibodies such as dupilumab are currently under investigation for CHE treatment, with early promise. Management of CHE will likely move toward more targeted treatments through clinical trials and away from broad immunosuppressants such as cyclosporine and methotrexate, which have previously been investigated for CHE and have more side effects. In coming years, CHE patients may benefit from a wider range of both topical and systemic therapeutics that target immune pathways relevant to the various CHE subtypes."

Journal • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis. (PubMed, Front Med (Lausanne)) - "Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments."

Clinical • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics • IL13 • IL4

Clinical activity, safety and tolerability of ASN002, a dual JAK/SYK inhibitor, in patients with non-Hodgkin lymphoma (NHL), myeolfibrosis (MF), chronic lymphocytic leukemia (CLL)and solid tumors. (ASCO 2018) - P1/2; "Pre-clinical studies indicate that ASN002 has low nM IC50s against SYK and JAK, decreases proliferation in ibrutinib-resistant cell lines, and suppresses tumor growth in rodent xenograft models of NHL and other hematologic malignancies. ASN002 was safe and well tolerated. Encouraging preliminary evidence of efficacy in NHL and MF patients was observed. Updated and detailed results will be presented."

Clinical • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Indolent Lymphoma • Mantle Cell Lymphoma • Myelofibrosis • Peripheral T-cell Lymphoma

COMPARING CUTANEOUS MOLECULAR AND CLINICAL IMPROVEMENT WITH DIFFERENT TREATMENTS IN ATOPIC DERMATITIS PATIENTS (ISAD 2021) - "Our objective was to identify an evidence-based approach to gauge therapeutic responses for individual AD patients, incorporating clinical and skin biomarker evaluations from studies with broad (cyclosporine, narrow-band ultraviolet B/NB-UVB, corticosteroids, ASN002/anti-JAK-SYK, crisaborole), and more targeted agents (dupilumab, fezakinumab/anti-IL-22). For instance, baseline CCL22 expression correlated with future clinical improvement across multiple treatments, including crisaborole, cyclosporine, and fezakinumab. This study advocates for combining clinical data and objective skin biomarkers to increase the ability to gauge responses in clinical trials and develop a precision medicine approach."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL2 • CCL22 • IL22 • SYK

[VIRTUAL] Not ‘Just Another Kinase’: The therapeutic potential of JAK inhibitors in the treatment of atopic dermatitis (SID 2021) - "Three studies examined abrocitinib; three studies examined bariticinib; one examined gusacitinib (ASN002), and another upadacitinib...Rapid symptom control, as early as the first and second week of initiation, was reported for abrocitinib and baricitinib. Given its rapid symptom control combined with a reassuring safety profile, we recommend considering the use of JAKi as a second-line systemic therapy for adult patients with moderate-severe AD who are unresponsive to topical treatment or biologic therapies."

Atopic Dermatitis • Dermatitis • Dermatology • Gastrointestinal Disorder • Immunology • Pediatrics • IL13 • IL4

Asana BioSciences to Present Additional Efficacy Data from Chronic Hand Eczema Phase 2b Trial of Oral SYK/JAK Inhibitor Gusacitinib at AAD VMX Late-Breaking Session (Businesswire) - "Asana BioSciences...announced that it will present additional positive results from a Phase 2b study evaluating the efficacy and safety of its investigational oral Janus kinase family (JAK) and spleen tyrosine kinase (SYK) inhibitor gusacitinib (ASN002) in adult patients with moderate-to-severe chronic hand eczema (CHE) in a late-breaking research program at the American Academy of Dermatology Virtual Meeting (AAD VMX 2021), to be held April 23 – 25, 2021."

P2b data • Atopic Dermatitis • Dermatology • Immunology

JAK inhibitors for atopic dermatitis: a promising treatment modality. (PubMed, Clin Exp Dermatol) - "Oral formulations include abrocitinib, upadacitinib, baricitinib, and gusacitinib and are most appropriate for patients with moderate-to-severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment modality to revolutionize the management of AD."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • JAK1 • JAK2 • JAK3 • TYK2

Asana BioSciences’ Gusacitinib Granted FDA Fast-Track Designation for Moderate-to-Severe Chronic Hand Eczema (Businesswire) - "Asana BioSciences...announced today that the U.S. Food and Drug Administration (FDA) has granted Fast-Track designation to Asana’s gusacitinib (ASN002)...for the treatment of moderate-to-severe Chronic Hand Eczema (CHE)....'We look forward to taking advantage of the potential expedited review offered by FDA Fast-Track and initiate phase 3 pivotal studies to support marketing authorization in the second half of 2021.'"

Fast track designation • New P3 trial • Atopic Dermatitis • Dermatology • Immunology

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. (PubMed, Ther Clin Risk Manag) - "CHE represents a major challenge for physicians and patients alike, and efforts to improve the minimally invasive diagnostic tools and treatment paradigms are ongoing. In the near future, CHE patients may benefit from new topical and systemic therapeutics that specifically target abnormally expressed immune markers."

Journal • Review • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immunology

"Gusacitinib, a novel oral inhibitor of multiple inflammatory pathways, achieved rapid and clinically meaningful improvement in chronic hand eczema. https://t.co/B33wCHW2ua #EADV2020" (@MedscapePharm)

Clinical • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immunology

JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results. (PubMed, Microorganisms) - "The treatment of AD reflects the pathogenetic disorders, starting from basic emollient therapy, and goes to topical anti-inflammatory regimens followed by phototherapy, systemic immunosuppressive drugs, and new biologic immunomodulators. This paper will thus summarize the novel collection of biological treatment JAK-STAT inhibitors dedicated to AD."

Clinical • Journal • Review • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation • Pediatrics • Pruritus • Sleep Disorder

[VIRTUAL] A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Gusacitinib (ASN002) in Subjects with Moderate-to-Severe Chronic Hand Eczema (EADV 2020) - No abstract available

Clinical • Late-breaking abstract • P2b data • PK/PD data • Atopic Dermatitis • Contact Dermatitis • Dermatology • Immunology