C21 Improved Blood Flow in People With Raynaud’s Secondary to Scleroderma

Oral treatment with C21 restored hand temperature by improving blood flow  in people with Raynaud’s phenomenon secondary to scleroderma, top-line data from a Phase 2 clinical trial show.

“The results of the phase II study show that C21 can directly increase blood flow in fibrotic tissue,” Carl-Johan Dalsgaard, CEO of Vicore Pharma,  treatment developer, said in a press release. “This further differentiates C21 from competitors.”

C21 (VP01) works by activating the angiotensin II receptor type 2 (AT2R), a protein receptor that, when active, promotes blood vessel widening —  vasodilation — and counteracts tissue scarring (fibrosis).

Almost all scleroderma patients develop Raynaud’s phenomenon, a condition that causes the fingers and toes to become numb and frigid in response to low temperatures or stress. This is induced by the excess collagen that narrows small blood vessels in the fingers and toes.

Through its mechanism of action, C21 is expected to promote blood vessel widening, ultimately improving blood flow in people with this condition.

The double-blind Phase 2 trial (NCT04388176) evaluated the vasodilatory effect of a single dose of C21 on Raynaud’s phenomenon in 12 adults with scleroderma. On average, the patients had at least five weekly Raynaud’s phenomenon flare-ups during the winter months.

In the study, their hands were immersed in cold water — called a cold challenge — so the researchers could assess the effect of the therapy in improving blood flow, by measuring the time each finger rewarmed comparatively to a placebo.

Patients treated with C21 showed greater skin temperature recovery 15 minutes after the cold challenge, indicating an improvement in dilation of the vessels. In fact, the rate of temperature recovery in the treated group was still rising after 15 minutes. According to the scientists, this strongly suggests that the experimental design did not fully capture the effect of C21.

These results support the broader usefulness of C21 in improving blood flow in fibrotic tissue in people with vascular diseases (disorders of the blood vessels), the team added.

“These findings are potentially very exciting and suggest that C21 increases blood flow in patients with microvascular disease,” said Ariane Herrick, professor at the University of Manchester, in England, and the trial’s lead investigator.

C21 also is being explored as a treatment for people with idiopathic pulmonary fibrosis (IPF) or COVID-19 infection.

Previous studies in lung tissue samples taken from an IPF patient indicated the role of C21 in blocking a molecule called transforming growth factor-beta 1, a key mediator of fibrosis.

In addition, this therapy was effective in reducing tissue fibrosis in animal models of pulmonary fibrosis and pulmonary hypertension.