Povetacicept shows promise in MG mouse model

Alpine Immune Sciences' experimental therapy also fared well in a Phase 1 trial

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with the experimental therapy povetacicept (ALPN-303) reduced disease activity in a mouse model of myasthenia gravis (MG), according to data shared by its developer, Alpine Immune Sciences.

Povetacicept also was tolerated well by healthy volunteers participating in a Phase 1 clinical trial.

“Together, these data provide strong rationale for the advancement of povetacicept in myasthenia gravis and other autoimmune and/or autoantibody-related neurological conditions,” Stanford Peng, MD, PhD, said in a press release. Peng is president and head of research and development at Alpine Immune Sciences.

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“There is a clear need for more safe, efficacious, and conveniently dosed therapies for myasthenia gravis and related diseases, and we look forward to the future opportunity to include them in the povetacicept development program,” Peng said.

Findings were presented last week at the 148th Annual American Neurological Association (ANA) meeting, in a poster titled, “Povetacicept (ALPN-303), a Potent Dual BAFF/APRIL Antagonist, for the Treatment of Myasthenia Gravis (MG) and Other Antibody-Related Neurological Diseases.”

MG is caused by the immune system making self-targeting antibodies that interfere with the communication between nerve and muscle cells, ultimately resulting in muscle weakness and other symptoms. Most cases of MG are specifically driven by antibodies that target the acetylcholine receptor (AChR).

Antibodies are produced mainly by a type of immune cell called B-cells. Povetacicept is designed to reduce the activity of B-cells by simultaneously blocking the activity of two signaling molecules that promote B-cell survival and activation: one called BAFF (B-cell activating factor) and another called APRIL (a proliferation-inducing ligand).

Testing povetacicept in a mouse model of MG

A team led by scientists at Alpine tested povetacicept in a mouse model of MG. Animals received a vaccine to induce an immune attack targeting AChR.

Results showed that povetacicept significantly reduced levels of all types of antibodies, including anti-AChR antibodies, in this model. Treated mice also had significantly lower clinical scores, suggesting less-severe symptoms.

Scientists also conducted a Phase 1 clinical trial, called RUBY-1 (NCT05034484), in which 72 healthy volunteers were given single doses of a placebo or povetacicept at doses ranging from 2.4 to 960 mg. The therapy was administered either intravenously (directly into the bloodstream) or subcutaneously (under the skin).

Results showed the therapy was well tolerated in general, with no serious side effects related to the medication reported. The most common side effects included headache and dizziness, which were mostly mild.

Findings also indicated that povetacicept was working as expected. The therapy reduced the activity of APRIL and BAFF, lowered the number of antibody-producing cells, and decreased total antibody levels. Data also suggested that a dose of 80 to 240 mg, administered via an under-the-skin injection every four weeks, likely would be effective for controlling antibody-driven diseases like MG.

Based on these findings, researchers argued that “future clinical study of povetacicept in MG and other autoantibody-related neurological diseases is strongly supported.”