Enrollment to begin in Phase 1 trial of anti-inflammatory povetacicept

Basket study will enroll 42 adults with other autoimmune cytopenias

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Enrollment for a Phase 1b basket clinical trial of povetacicept (ALPN-303), an experimental anti-inflammatory therapy, for adults with cold agglutinin disease (CAD) and other autoimmune cytopenias is expected to start in the coming months.

That’s according to a corporate update from the treatment’s developer, Alpine Immune Sciences.

Basket trials evaluate a therapy in patients with various diseases that share a common molecular alteration. This type of study may accelerate the development of a therapy for multiple indications.

The Phase 1b basket study, called RUBY-4 (NCT05757570), will enroll 42 adults, 18 and older, with certain autoimmune cytopenias, a broad group of conditions wherein the immune system wrongly produces self-reactive antibodies that attack healthy blood cells.

Eligible autoimmune cytopenias include CAD and warm autoimmune hemolytic anemia — which both feature red blood cell destruction — as well as immune thrombocytopenia, where the autoimmune attack targets platelets.

RUBY-4 participants will receive monthly under-the-skin (subcutaneous) injections of povetacicept (240 mg) for six months, after which they can continue treatment in a six-month extension phase.

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The trial’s goal is to evaluate the therapy’s safety, effectiveness, pharmacokinetics (movement into, through, and out of the body), and pharmacodynamics (effects on the body).

The company recently launched a Phase 1 basket trial, called RUBY-3 (NCT05732402), to test the therapy in people with autoimmune glomerulonephritis, diseases marked by an autoimmune attack against the part of the kidney that filters blood, called glomeruli.

Povetacicept works by blocking two signaling molecules that promote the growth and activation of antibody-producing B-cells — B-cell activating factor (BAFF or BLyS) and a proliferation inducing ligand (APRIL).

By promoting B-cell depletion, the therapy should reduce the production of self-reacting antibodies that mediate the abnormal immune attacks in diseases like CAD.

“With the recent initiation of the RUBY-3 study in autoimmune glomerulonephritis and the imminent initiation of the RUBY-4 study in autoimmune cytopenias, 2023 is on track to be a pivotal year for Alpine and povetacicept, a potential best-in-class dual BAFF/APRIL inhibitor which we are developing for multiple autoantibody-related diseases,” said Mitchell H. Gold, MD, Alpine’s CEO and executive chairman. “We look forward to sharing updates on both studies anticipated by the end of the year.”

In preclinical studies of cellular and animal models, povetacicept showed a marked improved potency against BAFF, and particularly APRIL. It also was superior to molecules that suppress only BAFF or APRIL and Telitacicept, a dual BAFF/APRIL inhibitor.

Data from Alpine’s-sponsored ongoing Phase 1 RUBY-1 trial (NCT05034484) in healthy volunteers showed the therapy was well tolerated when delivered subcutaneously or directly into the bloodstream up to 960 mg.

Early pharmacodynamic analyses showed reductions in circulating antibodies and antibody-secreting B-cells — outcomes never reported with other BAFF or APRIL suppressors in healthy adults, according to Alpine.

The data also supported the effectiveness of povetacicept when dosed subcutaneously once a month, a more convenient regimen than other BAFF and APRIL inhibitors.

“Our strong balance sheet and povetacicept’s promising preclinical and phase 1 healthy volunteer data, in addition to a convenient once every four-week subcutaneous dosing regimen, enables us to advance a robust development plan which has the potential to bring a meaningful new therapeutic option for patients living with multiple different autoimmune or inflammatory diseases,” Gold said.

The company is also testing povetacicept in people with systemic lupus erythematosus.