Profervia granted FDA orphan drug status as treatment for SSc

Calcium channel blocker seen to ease SSc symptoms such as Raynaud's
by Margarida Maia, PhD | September 10, 2024

The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Aisa Pharma’s Profervia (cilnidipine), an investigational oral calcium channel blocker also known as AISA-021, for the treatment of systemic sclerosis (SSc).

In its request package for the designation, the company included data from an ongoing Phase 2 clinical study called RECONNOITER (ACTRN12621000459820) in which Profervia is showing benefits in easing symptoms of SSc. Among the symptoms reduced is Raynaud’s phenomenon, which causes pain and tingling in the hands and fingers.

“We hope this designation will accelerate our development program for AISA-021, which is designed to provide a once-daily, well-tolerated, and economical treatment that we hope can improve the lives of patients with SSc,” Andrew Sternlicht, MD, Aisa’s CEO and founder, said in a company press release.
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The granting of orphan drug status provides an incentive for companies to develop products for rare diseases. The designation’s benefits include tax credits and a potential seven years of market exclusivity should the treatment ultimately be approved. According to Sternlicht, the company believes this is “the first time” a calcium channel blocker has been granted such a designation for an autoimmune disease.

Profervia now being tested for SSc in trial in Australia
In SSc, also known as scleroderma, tissue scarring and thickening can cause damage to small blood vessels and poor blood flow to the body’s extremities. This often results in Raynaud’s phenomenon, where the blood stops flowing properly to the fingers and toes, causing them to feel numb. There are no approved treatments for Raynaud’s.

Profervia contains cilnidipine, a calcium channel blocker that’s used to treat high blood pressure in some Asian countries, but hasn’t been approved to date in the U.S. Aisa is working to repurpose it for SSc and has scheduled a meeting with the FDA this month to discuss the next steps for potentially bringing Profervia to the market in this country.

As a calcium channel blocker, Profervia stops calcium from entering cells in the heart and blood vessels, allowing them to relax and widen. This helps increase blood flow to tissues across the body.

Unlike other calcium channel blockers, Profervia may have broader effects, including the potential to ease pain, commonly experienced by people with Raynaud’s.

In the first part of the RECONNOITER study, which is running at two hospitals in Australia, 60 adults with Raynaud’s secondary to SSc were randomly assigned to receive Profervia (10 or 20 mg), alone or in combination with tadalafil (5 mg), or a placebo. The medication is being taken once a day as a tablet or capsule, for 12 days.

In addition to being well tolerated, Profervia worked better than the placebo or other calcium channel blockers often used off-label in SSc to reduce the frequency of Raynaud’s episodes. The 20 mg dose eased a range of symptoms, as reported by patients, while adding tadalafil improved efficacy with 10 mg, but not 20 mg, the data showed.

Tadalafil is a medication that can relax and widen blood vessels, improving circulation and lowering blood pressure. It is sold under the brand name Cialis to treat erectile dysfunction, and as Adcirca, Tadliq, and Alyq for pulmonary arterial hypertension.

The second part of RECONNOITER is testing the 20 mg dose of Profervia against a placebo in a crossover study. This means that patients first receive either Profervia or the placebo, and then switch, with those initially assigned to Profervia now given the placebo, and vice versa.

Early data by the National Institutes of Health suggest that Profervia has no potential for abuse, meaning it could be a safer option for pain relief without the risks of addiction that come with opioids. Aisa plans to present additional data at a scientific conference in Washington, D.C., this November, the company said.
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Aisa now is seeking partners and investors to help bring Profervia to market. “We are actively seeking a development partner and investors to support bringing this much-needed treatment to patients,” Sternlicht said.