Aisa Pharma's AISA-021 Shows Promise in Phase 2 Trial for Systemic Sclerosis-Associated Raynaud's Phenomenon
Key Insights
Aisa Pharma (search)'s Phase 2 RECONNOITER trial of AISA-021 (cilnidipine) demonstrated significant improvements in attack-free days and reduced duration of Raynaud's attacks in patients with systemic sclerosis (search)-associated Raynaud's phenomenon (search).
While the primary endpoint of reducing weekly attack frequency did not reach statistical significance, AISA-021 showed a 22.1% reduction compared to 12.4% with placebo and was well-tolerated with no treatment-related serious adverse events.
The company plans to meet with the FDA to discuss Phase 3 study design and potential registration pathway for this orphan drug-designated treatment targeting a condition with no approved therapies.
Aisa Pharma (search) announced encouraging results from its Phase 2 RECONNOITER trial of AISA-021 (cilnidipine), a novel once-daily calcium channel (search) blocker for treating systemic sclerosis (search)-associated Raynaud's phenomenon (search) (SSc RP). The findings were presented at the 9th World Systemic Sclerosis Congress in Athens, Greece, marking a significant step forward for patients with this debilitating condition that currently has no approved treatment options.
Trial Design and Patient Population
The Phase 2 RECONNOITER clinical trial was a randomized, double-blind, placebo-controlled, prospective crossover study that enrolled 64 patients with active SSc RP. The study was conducted in two parts: Part A evaluated dose levels (10 mg and 20 mg), safety, efficacy, and co-administration with a PDE-V inhibitor using a parallel arm design, while Part B assessed safety and efficacy in 37 patients using a randomized crossover design.
Notably, 70% of treated patients were already receiving stable treatment for their Raynaud's systemic sclerosis (search) symptoms, and AISA-021 was added to their existing regimens. The primary endpoint measured the change from baseline in the mean weekly number of Raynaud's attacks, with key secondary endpoints including severity, duration, Raynaud's condition score, pain, and attack-free days.
Key Efficacy Results
While the primary endpoint did not reach statistical significance, AISA-021 demonstrated meaningful clinical benefits across multiple measures. Patients treated with AISA-021 showed 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 (p = 0.10).
More significantly, AISA-021 demonstrated a statistically 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 (p = 0.013). The treatment also significantly reduced the duration of Raynaud's attacks (p = 0.02) and improved thermographic assessment of skin temperature measured at the proximal interphalangeal joint level (p = 0.047).
Broader Systemic Benefits
Beyond Raynaud's-specific improvements, AISA-021 showed numerical benefits in treating broader systemic sclerosis (search) symptoms. Using the SHAQ PRO instrument for SSc, the treatment demonstrated improvements over placebo in all-cause pain, gastrointestinal dysfunction, disability, overall SSc disease severity, and breathing difficulties.
"I am particularly encouraged by these strong results because 70% of treated patients were already on stable treatment for their Raynaud's systemic sclerosis (search) symptoms, and AISA-021 demonstrated meaningful improvements on top of these existing regimens," said Professor Francesco Del Galdo, Head of the Scleroderma (search) Program at Leeds University and former President of EUSTAR.
Safety Profile and Tolerability
AISA-021 was generally well-tolerated throughout the study, with a safety profile comparable to placebo. Importantly, no treatment-related serious adverse events occurred in any of the treatment groups, supporting the drug's potential for long-term use in this patient population.
Responder Analysis and Clinical Significance
A responder analysis revealed that over twice as many AISA-021-treated patients achieved a ≥70% reduction in attack frequency or meaningful improvement on a Raynaud's symptom questionnaire compared to placebo-treated patients, highlighting the treatment's potential for clinically meaningful outcomes.
Regulatory Path Forward
Based on these encouraging results, Aisa Pharma (search) intends to meet with the U.S. FDA and other regulatory authorities in an End of Phase 2 meeting to define the Phase 3 clinical study design and potential registration pathway for AISA-021 in SSc RP.
"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," said Andrew Sternlicht, Founder and Chief Executive Officer of Aisa Pharma (search). "These encouraging results provide strong support for advancing to Phase 3 studies."
About the Disease and Unmet Need
Systemic sclerosis (search) is the most fatal of autoimmune illnesses, affecting 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 (search) is characterized by decreased blood flow, often triggered by cold temperatures, causing severe pain, tingling, and numbness in the hands and fingers. Currently, no oral drug has been approved worldwide for the treatment of Raynaud's phenomenon.
Drug Development and Mechanism
AISA-021 is a novel, once-daily, investigational oral dual calcium channel (search) inhibitor designed to promote vasodilation and endothelial homeostasis while reducing neuronal signaling, inflammation, and sympathetic activation. Originally approved in Japan in 1995 for hypertension (search) treatment, Aisa Pharma (search) has developed a proprietary process to improve the drug substance and created a new formulation specifically designed to treat Raynaud's phenomenon (search). The treatment has received Orphan Drug Designation from the U.S. FDA for systemic sclerosis (search) treatment.