New Hope for Scleroderma Patients as AISA-021 Trial Shows Significant Symptom Relief

BOSTON, MA – March 06, 2026 – In a significant development for patients suffering from one of the most debilitating aspects of systemic sclerosis, Aisa Pharma has announced encouraging results from a Phase 2 trial of its investigational drug, AISA-021. While the study narrowly missed its primary target, the drug demonstrated substantial improvements in key patient-centric outcomes, including a dramatic increase in attack-free days and a reduction in the duration of painful episodes associated with Raynaud's phenomenon.

The findings, presented at the 9th World Systemic Sclerosis Congress in Athens, Greece, offer a beacon of hope in a therapeutic area that has long been devoid of any approved oral treatments. For the roughly 100,000 people in the United States living with systemic sclerosis, a severe and often fatal autoimmune disease, this news marks a critical step toward addressing what many describe as their most burdensome symptom.

A Chilling Condition with No Approved Cure

Systemic Sclerosis (SSc), also known as scleroderma, is a chronic autoimmune illness where the body's immune system attacks its own tissues, leading to fibrosis (scarring) in the skin and internal organs. Nearly 95% of these patients experience a secondary form of Raynaud’s phenomenon, a condition characterized by vasospasm in the extremities, typically the fingers and toes. Triggered by cold or stress, these attacks restrict blood flow, causing the digits to turn white, then blue, and finally red upon rewarming. The experience is not just uncomfortable; it is intensely painful and can lead to non-healing digital ulcers and, in severe cases, amputation.

Currently, there are no FDA-approved oral therapies specifically for SSc-associated Raynaud's. Physicians rely on off-label use of medications designed for other conditions, primarily calcium channel blockers (CCBs) like nifedipine or phosphodiesterase 5 (PDE5) inhibitors such as sildenafil. While these can offer some relief, their efficacy is often limited, and they come with a high burden of side effects, including headaches, flushing, and swelling, leading to discontinuation in as many as 30% of patients.

This landscape of high unmet need is the backdrop for Aisa Pharma's RECONNOITER trial, which evaluated AISA-021, a novel, once-daily formulation of the drug cilnidipine.

Decoding the RECONNOITER Trial Results

The Phase 2 RECONNOITER study was a randomized, double-blind, placebo-controlled trial involving 64 patients. Its primary goal was to measure the change in the average number of weekly Raynaud's attacks. On this front, the results did not achieve statistical significance. Patients taking AISA-021 saw a 22.1% reduction in weekly attacks compared to 12.4% in the placebo group, a difference that, while numerically superior, had a p-value of 0.10, just outside the traditional threshold for significance.

However, a deeper look into the secondary endpoints reveals a more compelling story. The drug achieved a statistically significant, placebo-adjusted increase of over 155% in the proportion of attack-free days (p=0.013). This translated to a nearly four-fold improvement from baseline for patients on the treatment. Furthermore, the duration of the painful attacks was also significantly reduced (p=0.02).

"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, M.D., Founder and CEO of Aisa Pharma, in a statement. He emphasized that the drug improved pain and other symptoms while maintaining a favorable safety profile comparable to placebo, with no serious adverse events related to the treatment.

A Novel Mechanism and a Strategic Path Forward

What sets AISA-021 apart is its unique mechanism of action. The drug, cilnidipine, is a dual calcium channel inhibitor. While it blocks the L-type calcium channels to relax blood vessels, similar to other CCBs, it also blocks N-type calcium channels. These N-type channels are involved in the sympathetic nervous system's release of norepinephrine, a key neurotransmitter that constricts blood vessels during a stress response. By inhibiting both pathways, AISA-021 may offer a more comprehensive approach to preventing vasospasm.

Originally approved in Japan in 1995 for hypertension, Aisa Pharma has developed a proprietary, high-purity formulation of cilnidipine specifically for Raynaud's. The company has already been granted Orphan Drug Designation by the FDA for its use in Systemic Sclerosis, a status that provides incentives for developing treatments for rare diseases.

Professor Francesco Del Galdo, a leading scleroderma expert at Leeds University who presented the data, highlighted the clinical relevance of the findings. "Attack‑free days and attack duration are highly relevant endpoints in SSc RP and align with contemporary outcome‑measure and patient-reported outcome guidance," he noted. "We believe attack‑free days can serve as a primary endpoint in pivotal studies."

Critically, he pointed out that 70% of patients in the trial were already on other stable treatments for Raynaud's, meaning AISA-021 demonstrated its benefits on top of the current standard of care. This robust effect suggests the drug could be a powerful new tool for clinicians. Professor Del Galdo also suggested that based on the data, a successful pivotal Phase 3 study could potentially be conducted with fewer than 100 patients.

Beyond Raynaud's: Broader Implications

The potential benefits of AISA-021 may not be limited to Raynaud's. The trial data also showed numerical improvements in other systemic sclerosis symptoms, including all-cause pain, gastrointestinal dysfunction, and breathing difficulties. This hints at a broader disease-modifying potential that the company plans to explore in the future.

With these encouraging results in hand, Aisa Pharma now intends to meet with the FDA and other global regulators to discuss the design of a Phase 3 trial and map out a potential path to registration. As the company seeks to secure Series A funding to advance its lead program, the findings from the RECONNOITER trial provide a strong foundation. For the thousands of patients who endure the daily pain and disruption of Raynaud's, the prospect of the first-ever approved oral therapy represents a long-awaited and potentially life-changing breakthrough.