Asana BioSciences’ investigational oral Janus kinase family (JAK) and spleen tyrosine kinase (SYK) inhibitor gusacitinib (ASN002) showed rapid and significant improvement in a phase 2b study of 97 adult patients with moderate-to-severe chronic hand eczema.
The study was a randomized, double-blind, placebo-controlled, parallel-group study evaluating oral gusacitinib (40 mg or 80 mg once daily) for up to 32 weeks, with the primary endpoint of mean modified total lesion severity score (mTLSS) at week 16 (NCT03728504).
The topline results show that gusacitinib achieved a dose-dependent, clinically meaningful, and statistically significant improvement relative to placebo in both the primary and key secondary endpoints of efficacy. Gusacitinib 80 mg resulted in an overall decrease of 69 percent (p<0.005) in mTLSS from baseline, compared to a 49 percent decrease for 40 mg and 33 percent decrease for placebo.
Both 40 and 80 mg doses resulted in 50 percent and 66 percent improvement, respectively, in the mTLSS pruritus sub-score at week 16. Topline results also show significant improvement in key secondary measures such as Physician’s Global Assessment (PGA) with a 5-fold increase in subjects achieving clear or almost clear over placebo at 80 mg dose. Rapid and clinically relevant reductions in mTLSS (p<0.005), PGA (p<0.05) and pruritus were observed as early as 4 weeks and sustained for the duration of the study.
Safety results show that both doses of gusacitinib were well tolerated. The most common treatment-emergent adverse events observed were upper respiratory tract infection, headache, nausea, and nasopharyngitis. No pulmonary embolism was reported in the gusacitinib groups. No opportunistic infections, malignancies, major adverse cardiovascular events (MACE), or deaths were reported in the study.
“Chronic hand eczema (CHE) is a debilitating condition that affects approximately 10% of the U.S. population and millions of people worldwide. Patients with CHE suffer greatly from this disease, which limits their ability to work and perform activities of daily living. Currently there are no approved treatments in the U.S., and therapies used for this condition are not very effective,” says Emma Guttman-Yassky, M.D., Ph.D., Sol and Clara Kest Professor of Dermatology, Vice Chair, Department of Dermatology, Director of the Center for Excellence in Eczema and Director of the Laboratory of Inflammatory Skin Diseases in the Department of Dermatology at Icahn School of Medicine at Mount Sinai in New York, in a news release. “Disease drivers of CHE are multifactorial with genetics, atopy, contact allergens and irritating substances playing a role in ‘triggering’ the disease. JAK/SYK inhibitors, such as gusacitinib, can impact several pathways involved in inflammation of CHE and other dermatologic and inflammatory diseases, thus holding promise as potential therapeutics.”
“These topline findings are very impressive and provide evidence that gusacitinib, if approved, could be an effective new oral once-daily treatment option for patients suffering from chronic hand eczema who are unable to achieve adequate control with topical corticosteroids and other unapproved treatments. Gusacitinib showed a quick onset of efficacy, as significant improvements in both primary and key secondary endpoints were observed during the first four weeks of treatment, and these were sustained over the study period,” adds Howard Sofen, MD, Medical Director of Dermatology Research Associates, Associate Clinical Professor of Medicine/Dermatology, Geffen School of Medicine, UCLA, Consultant Dermatologist at LA County/Olive View Medical Center in Los Angeles, and one of the lead investigators of the Phase 2b study.
“We are excited by the results of this Phase 2b clinical study,” says Sandeep Gupta, PhD, Founder and CEO of Asana BioSciences. “Gusacitinib represents a First-to-Market opportunity for CHE as currently there are no approved treatments for this often-debilitating disease in the U.S. and many other major markets. We look forward to advancing gusacitinib to Phase 3 development and making it available for patients suffering from moderate-to-severe CHE.”
More about Gusacitinib
Gusacitinib, a potential best-in-class JAK/SYK inhibitor, has been studied in over 400 subjects to date including an earlier Phase 2b study (RADIANT) in 244 adult patients with moderate-to-severe atopic dermatitis and has shown good safety and tolerability. The RADIANT trial was a randomized, double-blind, placebo-controlled, parallel-group study evaluating three doses of gusacitinib (40, 60, and 80 mg once daily) over 12 weeks (NCT03654755). Gusacitinib showed a rapid and statistically significant reduction in pruritus as well as a statistically significant reduction in EASI score from baseline in moderate-to-severe AD patients.