New SSc drug safely cuts Raynaud’s attack duration, eases symptoms
But trial testing AISA-021 failed to meet its primary effectiveness measure
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Treatment with AISA-021 (cilnidipine), being developed by Aisa Pharma for Raynaud’s phenomenon, safely reduced the frequency and duration of Raynaud’s attacks in people with systemic sclerosis (SSc).
That’s according to recently reported results from the Phase 2 RECONNOITER-1 trial (ACTRN12621000459820) — data that also showed that the once-daily oral therapy reduced Raynaud’s severity, as well as other SSc symptoms, such as digestive and breathing issues, among patients.
However, the reduction in patient-reported weekly Raynaud’s attacks, which was the trial’s primary efficacy measure, was not statistically significant compared with a placebo, the data show. That means the study did not meet its main goal.
These results were reported in an oral presentation at the 9th World Systemic Sclerosis Congress, held March 5-7 in Athens.
The company intends to discuss these Phase 2 results with regulatory authorities, including the U.S. Food and Drug Administration. AISA’s goal is to define a Phase 3 clinical study and discuss how to move forward to approve AISA-021 for SSc-related Raynaud’s phenomenon.
“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 [are] very encouraging,” Andrew Sternlicht, MD, Aisa‘s founder and CEO, said in a company press release detailing the findings.
Per AISA, a patient questionnaire found that more than twice as many participants on the therapy saw a reduction of at least 70% in attack frequency.
“These encouraging results provide strong support for advancing to Phase 3 studies,” Sternlicht said.
Raynaud’s ‘a highly burdensome manifestation of scleroderma’
SSc is characterized by the accumulation of scar tissue in the skin and internal organs. This can cause damage to small blood vessels and reduced blood flow to the body’s extremities, and may result in Raynaud’s phenomenon, a condition characterized by fingers and toes feeling numb, prickly, and cold in response to low temperatures or stress.
“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,” Sternlicht said.
AISA-021 contains cilnidipine, a calcium channel blocker that’s used under the brand name Profervia to treat high blood pressure in some Asian countries. It is not used for that indication in the U.S.
The therapy works by preventing calcium from entering cells in the heart and blood vessels, so that they can relax and widen; that is expected to help increase blood flow.
The RECONNOITER trial assessed the safety and efficacy of AISA-021 (10 mg and 20 mg) alone or in combination with tadalafil (5 mg) in individuals with secondary Raynaud’s phenomenon. Tadalafil is sold under the brand name Cialis to treat erectile dysfunction, and as Adcirca, Tadliq, and Alyq for pulmonary arterial hypertension.
The trial enrolled 64 participants divided into two groups. In Part 2A, 27 participants received 10 mg or 20 mg AISA-021 with/without tadalafil, or the placebo. In part 2B, the safety and efficacy of 20 mg AISA-021 was evaluated in 37 patients.
The results showed that AISA-021 treatment led to a 22.1 % reduction in the mean frequency of patient-reported weekly Raynaud’s attacks, compared with a 12.4% reduction in the placebo group. However, this did not reach statistical significance.
The scientists said that improvements with a placebo have occurred in previous trials in people with SSc and Raynaud’s phenomenon.
Attack-free days and attack duration are highly relevant endpoints in SSc [Raynaud’s phenomenon] and align with contemporary outcome‑measure and patient-reported outcome guidance.
Other measures also showed significant benefits, such as more days without Raynaud’s attacks and reduced attack duration.
Francesco Del Galdo, MD, PhD, head of the scleroderma program at Leeds University in the U.K., presented the results.
“Attack-free days and attack duration are highly relevant endpoints in SSc [Raynaud’s phenomenon] and align with contemporary outcome‑measure and patient-reported outcome guidance,” he said.
Safety of AISA-021 ‘comparable’ to a placebo, researchers say
AISA-021 treatment also eased pain, severity, and burden associated with Raynaud’s, as well as other non-Raynaud’s SSc symptoms, including overall SSc severity, digestive dysfunction, pain due to any cause, and breathing difficulties. AISA-021 was also generally well tolerated, with no treatment-related serious adverse events reported.
“Comparable safety to [a] placebo, and reduced dropouts distinguish AISA-021,” the scientists wrote. “We plan to advance AISA-021 into pivotal studies as it may be an efficacious, safe addition for SSc-RP and perhaps SSc.”
Del Galdo said he was “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.”
The FDA granted orphan drug status to AISA-021 for the treatment of SSc in 2024. The designation aims to incentivize companies to develop products for rare diseases by providing certain benefits, including tax credits and seven years of market exclusivity if the treatment is ultimately approved.
