Therapy Shows Potential to Block, Not Deplete, B-cells in Phase 1b Trial

PRV-3279, a potential therapy for people with systemic lupus erythematosus (SLE), durably blocks B-cells to prevent them from producing damaging antibodies, but does not deplete these key immune defense system cells, results from the first part of a Phase 1b/2 trial show.

The Phase 1b portion of the PREVAIL study (NCT03955666) assessed the therapy’s safety and pharmacological properties in healthy volunteers. Results also showed that Provention Bio‘s investigative treatment was well-tolerated.

The Phase 2a portion, testing PRV-3279 in people with SLE, is expected to begin in the first half of 2021, the company said.

PRV-3279 is an antibody-based molecule that targets and blocks the function of B-cells, a type of immune cell responsible for producing antibodies and key for immune protection.

In SLE, B-cells are dysfunctional and overreactive, resulting in the production of harmful antibodies directed against patients’ own tissues. This leads to excessive inflammation and organ damage.

Provention’s potential therapy is designed to target two receptors in the surface of B-cells, CD32B and CD79B. Blocking these two proteins is believed to inhibit B-cell function and suppress autoantibodies production. As such, it may regulate these cells and how they work without depleting them.

“These results build on prior clinical data with PRV-3279 and existing evidence of the role of CD32B in lupus. These data further increase our enthusiasm for this potentially groundbreaking treatment of B-cell driven immunologic conditions with high unmet need, such as lupus,” Francisco Leon, MD, PhD, co-founder and chief scientific officer of Provention Bio, said in a press release.

Phase 1b of PREVAIL was a double-blind and placebo-controlled  study of the therapy’s safety, pharmacokinetics (how a drug affects the body) and pharmacodynamics (how the body affects a drug) in 16 volunteers. Two  ascending doses were given every two weeks as intravenous infusions, or directly into the bloodstream.

Topline results showed that PRV-3279 was able to bind to circulating B-cells in a sustained, extensive, and dose-dependent manner.

The therapy’s use did not result in B-cell depletion, researchers reported. A reduction in the blood levels of immunoglobulin M, a type of antibody, was also seen.

“We believe that PRV-3279 is uniquely differentiated to allow for rapid and durable inhibition of activated B cells without depletion …  PRV-3279 may therefore, ultimately strike an optimal balance between safety and efficacy in lupus and other B cell-mediated autoimmune disorders,” Leon said. 

Both doses tested led to the production of antibodies against the therapy, but this did not affect the safety and pharmacological properties of the therapy, thee scientists said.

“The data reported today provides a strong rationale to pursue this dual development path,” said Ashleigh Palmer, CEO and co-founder of Provention Bio.