Phase 2 trial of Profervia for Raynaud’s in SSc moves to part 2

Treatment found to reduce Raynaud's attacks in part 1 of trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Aisa Pharma has launched the second part of its Phase 2a trial evaluating Profervia (cilnidipine) — an oral medication that showed positive safety and efficacy data in the study’s first part — as a treatment for Raynaud’s phenomenon in people with systemic sclerosis (SSc).

Raynaud’s is a common manifestation of SSc that’s characterized by coldness, numbness, and tingling in the fingers and toes in response to cold or stress.

The announcement comes shortly after the company presented that positive data, from the RECONNOITER trial (ACTRN12621000459820), at a conference in Europe earlier this month. In the trial’s part one, the daily oral treatment was found to lower Raynaud’s attack frequency and ease SSc severity, in addition to being well tolerated.

RECONNOITER  is testing Profervia in adults with Raynaud’s disease secondary to SSc at two hospitals in Australia.

“We are excited to move forward with the second part of our Phase 2 study, and encouraged by the data … which demonstrated that Profervia may provide significant relief to patients with SSc-[Raynaud’s],” Andrew Sternlicht, MD, CEO and founder of Aisa, said in a company press release, adding, “We will continue to validate the biologic and scientific rationale and impact of treatment on overall disease course in SSc.”

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Aisa Pharma seeking to repurpose medication as Raynaud’s treatment

In people with SSc, also known as scleroderma,  the buildup of collagen — a connective tissue protein — can cause small blood vessels in the fingers and toes to narrow. Consequently, patients experience Raynaud’s phenomenon, in which blood flow to the extremities is restricted, leading to numbness and tingling.

“Almost all SSc patients suffer from Raynaud’s and new treatments are urgently needed given the high morbidity and burden of the disease,” Sternlicht said. 

Profervia is a novel formulation of cilnidipine, a fourth-generation calcium channel blocker that’s approved in some countries, namely China, India, Japan, and Korea, for the treatment of high blood pressure. It has never been approved for any indication in the U.S.

The once-daily oral medication induces blood vessel widening that helps increase blood flow to organs and tissues throughout the body.

Thus, Aisa is now seeking to repurpose the therapy for treating Raynaud’s in people with SSc.

Almost all SSc patients suffer from Raynaud’s and new treatments are urgently needed given the high morbidity and burden of the disease.

Its company’s RECONNOITER program is designed to assess the safety and efficacy of Profervia alone and in combination with tadalafil among 76 SSc-Raynaud’s patients.

Tadalafil belongs to a class of medications called phosphodiesterase inhibitors that help blood vessels relax and widen. It is sold under the brand name Cialis to treat erectile dysfunction, and as AdcircaTadliq, and Alyq to treat pulmonary arterial hypertension.

The first dose-finding part of RECONNOITER aimed to assess the safety and efficacy of Profervia and to identify the proper dose for the study’s second part.

Participants were randomly assigned to receive daily Profervia (10 or 20 mg), tadalafil (5 mg), a combination, or a placebo.

Results presented at a recent scientific conference indicated that Profervia was generally well tolerated and appeared to have a better safety profile than other commonly used calcium channel blockers.

Specifically, Profervia had a 17% incidence rate of adverse events in the study, compared with the 43% rate observed in a large meta-analysis of these other medications.

Profervia-treated patients experienced about a 43% reduction in weekly Raynaud’s attack frequency, compared with 18.9% among the placebo group, and 24% in the meta-analysis of other calcium channel blockers.

Moreover, Profervia at the 20 mg dose was associated with a reduction in patient-reported SSc severity relative to the placebo.

The addition of tadalafil increased treatment efficacy when combined with the 10 mg Profervia dose, but not the 20 mg dose.

A Data Safety and Monitoring Board reviewed data from these first 27 participants last summer. They selected the 20 mg dose for the study’s second part and recommended accelerating the trial’s pace, ending part 1 early and moving on to part 2.

Part 2 takes on a crossover study design, in which about 38 patients will initially be assigned to receive daily Profervia (20 mg) or a placebo, after which the groups will be switched. The entire study is expected to take 10 months.