Profervia (cilnidipine) / Aisa Pharma - LARVOL DELTA

A Re-Analysis of the RECONNOITER Phase 2 Trial of AISA-021 in the Treatment of Raynaud's Phenomenon Associated with Systemic Sclerosis - The Effects of Non-Specific Symptoms on Endpoints in Studies of Raynaud's Therapies (ACR Convergence 2026) - "The re-analysis using the specific attack definition suggested a stronger treatment effect than had been found with the non-specific attack definition and greatly decreased the variability and standard error associated with attack reporting, resulting in finding a reduction in weekly attack frequency that achieved statistical significance. Of the 31 patients in the study who received treatment with both AISA-021 and placebo treatment in either sequence in the crossover study, 4/31 (13%) saw a complete resolution of attacks while on AISA-021 and 9/31 (29%) had a reduction of 70% or more while being treated with cilnidipine. Regression to the mean could account for the improved placebo effect seen in period 2, though the treatment effect seen of AISA-021 when given in Period 2 was slightly less than seen in period 1."

P2 data • Cardiovascular • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis

Relative Evaluation of the benefit of Cilnidipine ON the Nature, Observational Indices, Temperature changes, and overall Effect in secondary Raynaud’s disease (RECONNOITER-1): Part B (ANZCTR) - P2 | N=38 | Completed | Sponsor: AISA Pharma Australia Pty. Ltd. | Recruiting ➔ Completed

Trial completion • Cardiovascular • Rheumatology

Aisa Pharma Announces Encouraging Results from Phase 2 RECONNOITER Trial of AISA-021 (Cilnidipine) in Patients with Systemic Sclerosis-Associated Raynaud's Phenomenon (PRNewswire) - "AISA intends to meet with the U.S. FDA and other regulators to determine the Phase 3 study design and potential registration pathway...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)..."

P2 data • Systemic Sclerosis

RECONNOITER-1: A PHASE 2, PROSPECTIVE, BLINDED, RANDOMIZED, PARALLEL-GROUP AND CROSSOVER CLINICAL TRIAL EVALUATING AISA-021, A NOVEL CCB, IN SUBJECTS WITH RAYNAUD'S PHENOMENON (SSC-RP) (SSWC 2026) - "We studied AISA-021(cilnidipine), a dual N + L-type CCB approved for hypertension in Japan in 1995 for SSc-RP...In Part A, 27 patients from two sites were rando- mized into six groups of 10 mg, 20 mg with/without tadalafil 5mg and placebo... In this first-in-class clinical trial for CTD-RP, significant impact on symptoms with ORAL COMMUNICATIONS 87 minimal side effects was found. Dual N- and L-type channel blocking actions, versus primarily L-type activity of approved CCBs, may explain this. CCB's exacerbate GI symptoms and were improved here."

Clinical • P2 data • Cardiovascular • Fibrosis • Hypertension • Inflammatory Arthritis • Rheumatology

Relative Evaluation of the benefit of Cilnidipine ON the Nature, Observational Indices, Temperature changes, and overall Effect in secondary Raynaud’s disease (RECONNOITER-1) (ANZCTR) - P2 | N=36 | Completed | Sponsor: AISA Pharma Australia Pty. Ltd. | Recruiting ➔ Completed | N=76 ➔ 36

Enrollment change • Trial completion • Cardiovascular • Rheumatology

AISA Pharma Announces Completion of Enrollment in Phase 2 RECONNOITER Trial of AISA-021 in Systemic Sclerosis-Related Raynaud's Phenomenon (PRNewswire) - "'We eagerly await the unblinding of the trial and full data analysis in February 2026.'...RECONNOITER Phase 2 results were accepted for an oral presentation at the World Congress on Systemic Sclerosis, which will be held March 5-7, 2026 in Athens, Greece....Aisa's patent for the treatment of Raynaud's and Systemic Sclerosis with AISA-021 and other drugs has issued in the EU, has received notice of allowance from Canada, and is in final review with the U.S. patent office."

Enrollment closed • P2 data • Patent • Systemic Sclerosis

Relative Evaluation of the benefit of Cilnidipine ON the Nature, Observational Indices, Temperature changes, and overall Effect in secondary Raynaud’s disease (RECONNOITER-1): Part B (ANZCTR) - P2 | N=38 | Recruiting | Sponsor: AISA Pharma Australia Pty. Ltd.

New P2 trial • Cardiovascular • Rheumatology

AISA 021, a Novel Calcium Channel Antagonist in Development for Raynaud's & Systemic Sclerosis, Has Antagonistic Activity at Sodium Channel Targets for Pain Relief and Treats Scleroderma Pain Better Than Current Calcium Channel Blockers in a Phase 2A Study (ACR Convergence 2024) - "An N-type antagonist, ziconotide, is approved for neuropathic pain...Cilnidipine at the clinical concentration obtained from pk samples in the ongong Phase 2A study was found to more potently inhibit Nav1.7 in the closed state than gabapentin, amlodipine and bupivacaine, at similarly clinically relevant plasma concentrations...On the pain domain of the SHAQ, cilnidipine 10 mg(n=4) reduced pain by 27% but 62% with tadalfil 5 mg(n=5) , 20 mg(n=3) increased pain 12% but decreased pain 24% with tadalafil 5 mg(n=4), and placebo patients(n=4) reduced pain 4%... Cilnidipine seems to have clinically relevant inhibitory properties at Nav 1.7 and may have this at Nav 1.8 as well, based on structure activity relationship analysis and pending experimental determination. In a preliminary Phase 2 study, encouraging effects were seen in pain relief as reported by patients in addition to a reduction in the weekly frequency of Raynaud's attacks. Clinicians often combine a CCB with a..."

P2a data • Cardiovascular • Immunology • Neuralgia • Pain • Rheumatology • Scleroderma • Systemic Sclerosis • NAV1

Preliminary Results from the RECONNOITER Trial, a Phase 2 Study of AISA 021 in the Treatment of Secondary Raynaud's, Primarily Due to Systemic Sclerosis (ACR Convergence 2024) - "Dose groups were AISA-021 10mg and 20mg, alone and with tadalafil 5mg, tadalafil alone and placebo...Results replicate the improved 24 year safety record of cilnidipine in hypertension treatment in the SSc-RP population. In this preliminary safety and efficacy study, AISA-021 was well-tolerated and efficacy trends were seen. A published metanalysis of CCB use for RP finds AE frequency of >46% and treatment discontinuation in >30% of patients. (P= 0.02 for AISA-021 superiority on safety c/w CCBs)."

P2 data • Cardiovascular • Gastrointestinal Disorder • Hypertension • Immunology • Pain • Rheumatology • Scleroderma • Systemic Sclerosis

AISA Pharma Receives FDA Orphan Drug Designation for AISA-021 for Treatment of Systemic Sclerosis (PRNewswire) - "Aisa Pharma, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to AISA-021(cilnidipine), a fourth-generation calcium channel antagonist. Aisa is developing AISA-021 for the treatment of Systemic Sclerosis (SSc), a rare disease, which impacts approximately 175,000 Americans and has the highest mortality rate of any autoimmune disease....A Pre-IND meeting with the FDA for AISA-021 in the treatment of Systemic Sclerosis and Secondary Raynaud's Phenomenon is scheduled for September 2024....Preliminary Results from the RECONNOITER Trial, a Phase 2 Study of AISA 021 in the Treatment of Secondary Raynaud's, Primarily Due to Systemic Sclerosis."

Orphan drug • P2a data • Immunology • Scleroderma • Systemic Sclerosis

Orphan Designation: treatment of systemic sclerosis (FDA) - Date Designated: 08/19/2024

Orphan drug • Systemic Sclerosis