XBiotech Launches Phase II Trial of Vilamakitug for Active Axial Spondyloarthritis Following FDA Clearance
Key Insights
XBiotech's IND application for the V-SPINE Phase II study of vilamakitug in active axial spondyloarthritis (search) completed FDA's 30-day review without a clinical hold, authorizing U.S. patient enrollment.
The double-blind, placebo-controlled trial will evaluate 400 mg subcutaneous vilamakitug weekly versus placebo in 150 participants, with ASAS40 response at Week 16 as the primary endpoint.
Vilamakitug is a True Human™ IgG4 monoclonal antibody targeting IL-1α, an upstream inflammatory mediator hypothesized to drive inflammation, bone erosion, and chronic pain in spondyloarthritis.
XBiotech Inc. (NASDAQ: XBIT) announced that its Investigational New Drug (IND) application for the V-SPINE study (PT064) has successfully completed the U.S. Food and Drug Administration's 30-day review period without a clinical hold, clearing the path for patient enrollment in the United States. The Phase II, double-blind, placebo-controlled, randomized trial will evaluate the efficacy and safety of vilamakitug in participants with active axial spondyloarthritis (search) (axSpA), marking the resumption of XBiotech's rheumatology program.
"FDA clearance of the PT064 protocol is a significant step forward for our vilamakitug program and for patients living with axial spondyloarthritis (search)," said Sushma Shivaswamy, Ph.D., Interim Chief Executive Officer and Chief Scientific Officer of XBiotech. "Vilamakitug is a True Human™ antibody indistinguishable from one naturally occurring in a healthy person with immunity to IL-1α, and we believe it represents a meaningful new approach to treating the inflammation that drives this disease."
Study Design and Endpoints
The V-SPINE trial (PT064) will enroll 150 adult participants with active axial spondyloarthritis (search), randomized to receive either 400 mg of vilamakitug administered as 16 weekly subcutaneous injections or placebo. The primary endpoint is the proportion of participants achieving an ASAS40 response at Week 16. The study also incorporates a 12-week open-label extension phase during which all participants will receive vilamakitug.
Despite the availability of approved biologic therapies, a substantial proportion of patients continue to experience inadequate disease control, representing what the company describes as a significant and persistent unmet medical need.
Scientific Rationale and Mechanism of Action
Vilamakitug, also known as XB2001 and Natrunix™, is an IgG4 monoclonal antibody that neutralizes interleukin-1α (IL-1α) (search), a proximal pro-inflammatory cytokine. In spondyloarthritis, IL-1α is hypothesized to contribute to synovial and entheseal inflammation, osteoclast-mediated bone resorption, cartilage degradation, and inflammatory joint pain. By targeting this upstream inflammatory mediator, vilamakitug is designed to potentially reduce both structural damage and disease activity, including in patients who have had an inadequate response to currently approved biologic therapies.
"The unmet need in axial spondyloarthritis (search) remains real and substantial," said Marina Magrey, M.D., PT064 Study Chair and Division Chief of Rheumatology at University Hospitals Cleveland Medical Center. "IL-1α is a compelling upstream target, hypothesized to play a role in the inflammation, bone erosion, and chronic pain that define this disease. The PT064 protocol is rigorously designed to test whether targeting this upstream pathway translates into meaningful clinical benefit."
Scientific Advisory Board
The clinical protocol was developed under the leadership of Study Chair Marina Magrey, M.D., who also serves as Professor of Medicine at Case Western Reserve University School of Medicine and Vice-Chair of the Spondyloarthritis Research and Treatment Network (SPARTAN). The distinguished advisory panel includes Atul Deodhar, M.D., of Oregon Health & Science University; Lianne S. Gensler, M.D., of the University of California, San Francisco; Walter P. Maksymowych, MB ChB, of the University of Alberta; Michael A. Paley, M.D., Ph.D., of Washington University in St. Louis; and John A. Carino, M.D., M.P.H., of Weill Cornell Medicine.
Company Background and Pipeline Context
XBiotech has a deep history in rheumatology. The company previously developed and clinically advanced bermekimab, a True Human™ anti-IL-1α antibody evaluated across multiple inflammatory diseases. On December 30, 2019, XBiotech sold bermekimab in a transaction valued at up to $1.35 billion, retaining the right to develop True Human™ anti-IL-1α antibodies in all areas of medicine outside of dermatology. PT064 represents the continuation of that rheumatology legacy, advancing vilamakitug as the company's next-generation True Human™ IL-1α antibody.
XBiotech's True Human™ antibodies are derived without modification from humans who possess natural immunity to certain diseases, sourced directly from the natural human immune response. The company is advancing a pipeline of therapies across inflammatory disorders, oncology, infectious disease, and dermatology.