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Aisa Pharma, Inc., a clinical-stage biopharmaceutical company focused on therapies for systemic sclerosis, announced results from its phase 2 RECONNOITER trial of AISA-021 (cilnidipine), a novel once-daily calcium channel blocker, for the treatment of systemic sclerosis-associated Raynaud's phenomenon (SSc RP). The results were presented in an oral presentation at the 9th World Systemic Sclerosis Congress held in Athens, Greece, from March 5–7, 2026.
"Systemic sclerosis-associated Raynaud's phenomenon remains a highly burdensome manifestation of scleroderma, with no approved treatment options and significant impact on function and quality of life," said Andrew Sternlicht, M.D., founder and chief executive officer of Aisa Pharma. "While the phase 2 study did not reach statistical significance on the primary efficacy endpoint in this small study, we believe the consistent effects observed with AISA-021 across a variety of key endpoints is very encouraging. AISA-021 showed significant improvements in the number of Raynaud's attack-free days and attack duration, which were higher than those seen with currently available calcium channel blockers. AISA-021 also improved pain and other Raynaud's symptoms, while maintaining a favourable safety profile. These encouraging results provide strong support for advancing to Phase 3 studies."
The Phase 2 RECONNOITER clinical trial (ACTRN12621000459820) is a randomized, double-blind, placebo-controlled, prospective, crossover study designed to assess the safety and efficacy of a once-daily oral AISA-021 in patients with active SSc RP. The study enrolled a total of 64 patients and was conducted in two parts, Part A, a phase 2A parallel arm design to evaluate dose (10 mg and 20 mg), safety, efficacy, and co-administration with a PDE-V inhibitor, and Part B, a phase 2 randomized crossover design to evaluate safety and efficacy in 37 patients. The primary endpoint was the change from baseline in the mean weekly number of Raynaud's attacks recorded, with key secondary endpoints including severity, duration, Raynaud's condition score (RCS), pain, and attack-free days. Patients were treated with standard of care therapies and AISA-021 was added on to their existing regimen.
Results from the RECONNOITER study demonstrated the following:
• On the primary endpoint, patients treated with AISA-021 demonstrated a 22.1 % reduction in the mean frequency of patient-reported weekly Raynaud's attacks compared to baseline, while placebo-treated patients had a 12.4% reduction, which did not reach statistical significance (p = 0.10)
• AISA-201 demonstrated a significant improvement in the proportion of attack-free days, with a more than 155% placebo-adjusted increase and nearly a four-fold improvement from baseline in attack-free day proportions (p?=?0.013)
• AISA-201 significantly reduced the duration of Raynaud's attacks (p=0.02) and thermographic assessment of skin temperature measured at the proximal interphalangeal joint (PIP) level (p=0.047)
• AISA-201 also improved non-Raynaud's symptoms measured with the SHAQ PRO instrument of SSc showing numerical benefit over placebo on parameters of all-cause pain, GI dysfunction, disability, overall SSc disease severity and breathing
• All measured Raynaud's metrics, including pain, severity, and burden, showed a numerical benefit with AISA-021–treated patients compared with placebo
• AISA-021 was generally well-tolerated, with no treatment-related serious adverse events (SAE) in all groups
Aisa Pharma intends to discuss these phase 2 results with the US Food and Drug Administration (FDA) and other regulatory authorities in an End of phase 2 (EOP2) meeting to define the phase 3 clinical study and potential registration pathway for AISA-021 in SSc RP.
"I am particularly encouraged by these strong results because 70% of treated patients were already on stable treatment for their Raynaud's systemic sclerosis symptoms, and AISA-021 demonstrated meaningful improvements on top of these existing regimens," said Professor Francesco Del Galdo, MD, PhD, the Head of the Scleroderma Program at Leeds University in the UK and former president of EUSTAR. "Attack-free days and attack duration are highly relevant endpoints in SSc RP and align with contemporary outcome-measure and patient-reported outcome guidance. We believe attack-free days can serve as a primary endpoint in pivotal studies, and the treatment effect and variability observed suggest that statistical significance in attack-frequency reduction could be achieved in a pivotal study with fewer than 100 patients. We also observed meaningful improvements in SSc beyond Raynaud's symptoms, including reductions in gastrointestinal symptoms, disease-related pain, and breathing difficulties, underscoring the potential of AISA-012."
AISA-021 is a novel, once-daily, investigational oral dual calcium channel inhibitor designed to promote vasodilation and endothelial homeostasis with reduced neuronal signalling, inflammation and sympathetic activation and thereby reduce vasospasm and ischemic injury in patients with systemic sclerosis–associated Raynaud's phenomenon (SSc RP). Originally approved in Japan in 1995 to treat hypertension, Aisa Pharma has developed a proprietary process to improve drug substance and a new formulation designed to specifically treat Raynaud's phenomenon. AISA-021 was granted Orphan Drug Designation from the US Food and Drug Administration (FDA) for the treatment of systemic sclerosis.
Beyond SSc RP, the company is planning to explore AISA-021 use in systemic sclerosis, acute treatment of Raynaud's, pulmonary fibrosis, ocular applications, and specific neuropathic pain indications, reflecting the central role of N-channel activity and antagonism in these disease's pathobiology.
Systemic sclerosis (SSc) is the most fatal of autoimmune illnesses and affects approximately 100,000 patients in the United States. Approximately half die of the disease within 12 years from diagnosis and 95% of SSc patients experience Raynaud's symptoms, which they describe as their most debilitating symptom. Raynaud's phenomenon is characterized by decreased blood flow, often as a result of exposure to cold temperatures, which can cause severe pain, tingling, and numbness in the hands and fingers. Cardiac, renal and vascular disease, which have been shown to improve in patients treated for hypertension with Cilnidipine, contribute to morbidity and mortality in patients with SSc. No oral drug has been approved in the world for the treatment of Raynaud's.
Aisa Pharma is a clinical-stage biopharmaceutical company dedicated to developing and commercializing new disease-modifying treatments for patients with serious rare diseases. The company's lead programme, AISA-021, is an investigational oral dual calcium channel inhibitor designed to promote vasodilation and support endothelial homeostasis.
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