About AISA-021

Aisa Pharma’s AISA-021 is a novel 4th generation dual channel calcium blocker being developed for the treatment of recurrent episodes of digital ischemia, known as Raynaud’s phenomenon, in patients with systemic sclerosis, the most severe form of Scleroderma.
The novel calcium blocker, cilnidipine is approved for treating hypertension in several Asian countries but has never been studied or developed to treat Systemic Sclerosis or Raynaud’s phenomenon previously. Compared to earlier generation calcium channel blockers that are approved worldwide, cilnidipine is better tolerated and safer in treating hypertension, with literally billions of doses in treating patients with high blood pressure over the last 31 years. While calcium channel blockers are prescribed for Raynaud’s they are not widely prescribed due to frequenct side effects and marginal efficacy. No studies of treating Raynaud’s with cilnidipine were done, prior to AISA’s efforts in its clinical trial programs The medical need to develop a treatment for the recurrent digital ischemic episodes that Sysetmic Sclerosis patients suffer from is clear from its life-altering impact on the quality of life of patients as well as the increased view that these episodes contribute to disease progression and ultimate morbidity and mortality.

Excitingly, cilnidipine has properties that distinguish it biologically from currently used calcium channel blockers and imply that it may be a better drug to treat Systemic Sclerosis and Raynaud’s than many other drugs, with a possible impact on not only digital ischemic episodes but other manifestations and contributors to disease pathology. The AISA study program may in the future demonstrate benefits on the pain of the disease, its impact on the GI system, renal dysfunction, vascular pathology, and fibrotic processes as well affecting the lungs and other organs.

AISA-021 Mechanism of Action

AISA-021 is a dual L and N channel selective calcium blocker, inducing vasodilating and venodilating effects and decreasing blood pressure in hypertensive patients, but not in normotensive individuals. US-approved CCBs primarily target L-channel receptors, but AISA-021 has >50~500 X more activity at the N channel than these agents. This is key to its unique profile and benefits as the N channel is located throughout the body in the spinal cord, the kidney, the heart, on veins and on the endothelium (the inside of arteries) and in various other tissues. Studies have demonstrated that in addition to its blood pressure lowering effect, cilnidipine has beneficial effects on kidney function, atherosclerosis, cardiac function, and nervous system (autonomic or non-voluntary) functioning. All of these body systems are adversely affected in patients with scleroderma.
Recent publications have highlighted the potent antifibrotic effects of certain calcium channel blockers like AISA-021, and we believe that AISA-021’s increased N channel blockade may result in additional antifibotic potency beyond these currently available calcium channel antagonists. We are investigating these activities, and comparing cilnidipine’s antifibrotic potency compared to approved antifibrotic treatments. In fact, a population survey in Korea of almost 400,000 people showed that any use of calcium channel blockers was an approximate 32% reduced risk for developing pulmonary fibrotic diseases.

Orphan Drug Designation

The US FDA has designated AISA-021 as an orphan drug for the treatment of systemic sclerosis(SSc). This means that the FDA considers systemic sclerosis to be an orphan disease (affecting <200,000 people in the United States) and that they have reviewed the evidence of efficacy and safety for AISA-021 in treating systemic sclerosis ( this can be in pre-clinical or clinical studies but in the case of AISA-021 was based on the preliminary data generated in the Phase 2 RECONNOITER Study in SSc patients as well as studies of the drug in animal and clinical settings demonstrating beneficial effects of relevance to SSc disease pathology and progression) and concluded that it is medically plausible that AISA-021 could treat SSc.
The benefits of Orphan Designation of AISA-021 for the company are the granting of increased market exclusivity in the US and territories ( 7 vs the 5 year standard that accompanies new drug approvals), priority review of the NDA and regulatory assistance from the FDA, tax credits, potential for breakthrough designation, and the waiving of PDUFA fee application for the NDA when submitted.
Aisa will also apply for Orphan Drug Designation for AISA-021 in the EU, which provides similar benefits except that the marketing exclusivity period is extended to 10 years in EU countries.

Pediatric Raynaud’s Study Plan

Aisa is planning on beginning a study in pediatric patients with Raynaud’s. Although Raynaud’s symptoms are certainly less prevalent in children than in adults, as many as 30% of pediatric patients presenting with Raynaud’s symptoms may have secondary Raynaud’s and an underlying connective tissue disease and recommendations are that these children are followed carefully. Just like in adults, there are no good medical treatments for children with Raynaud’s and poor tolerance of vasodilator drugs and minimal efficacy of these agents highlights the need for an improved therapy. Aisa is planning on conducting a pediatric trial to begin in 2026 to discover whether AISA-021 might produce efficacy and safety for the treatment of Raynaud’s in children that mirrors the results witnessed to date in the Phase 2 RECONNOITER trial in secondary Raynaud’s patients in Australia.