Phase 2 trial tests tibulizumab in adults with diffuse SSc

Dual-pathway treatment aims for greater efficacy, benefit
by Andrea Lobo, PhD | January 7, 2025

​Zura Bio has launched a Phase 2 trial to evaluate the safety and efficacy of tibulizumab, its experimental dual pathway antibody to treat systemic sclerosis (SSc).

The TibuSURE trial is expected to enroll as many as 80 adults with early diffuse cutaneous SSc. They will receive tibulizumab or a placebo for 24 weeks (about six months). This will be followed by an open-label extension of 28 weeks, in which all participants will receive the treatment.

“We believe tibulizumab’s dual-pathway approach holds the potential to be best-in-class, aiming to provide deeper efficacy and greater benefits for patients affected by this life-threatening autoimmune disease,” Kiran Nistala, PhD, Zura Bio’s chief medical officer and head of development, said in a company press release. “The initiation of the TibuSURE study marks a significant milestone in addressing certain urgent, unmet needs of this patient population and advancing our mission to improve the lives of those affected by autoimmune and inflammatory conditions.”

SSc is an autoimmune disease characterized by inflammation and fibrosis, or the accumulation of scar tissue in the skin and internal organs, such as the lungs, heart, kidneys, and digestive tract.
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Two therapies (Ofev and Actemra) are available to treat severe lung complications associated with the disease, but there is no approved treatment for multiple organ manifestations.

​Combined approach
Tibulizumab (ZB-106) is a humanized, dual-antagonist antibody designed to bind and block two proteins, interleukin (IL)-17A and B-cell activating factor (BAFF). It results from a fusion of ixekizumab (approved as Taltz to treat the autoimmune conditions plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis), an antibody that binds IL-17A, and tabalumab, which binds BAFF.

Zura says tibulizumab’s combined approach to address signaling from immune T-cells and B-cells might increase clinical benefit. The treatment is administered by subcutaneous (under-the-skin) injection, once every four weeks.

“Tibulizumab’s dual-targeting mechanism offers a novel strategy by concurrently targeting two pivotal pathways involved in inflammation and fibrosis,” said Christopher Denton, PhD, professor at University College London and rheumatologist at the Royal Free Hospital, London. “This mechanism holds the potential to address the multi-organ pathology [processes] of SSc and help improve the lives of patients.”

A total of 78 participants have been dosed with tibulizumab in three Phase 1b trials in people rheumatoid arthritis or Sjögren’s disease, according to the company. The treatment demonstrated an acceptable safety profile, with no new findings compared with antibodies targeting either IL-17A or BAFF.

The TibuSURE trial’s primary goal is to assess the therapy’s efficacy at reducing skin fibrosis, assessed by the modified Rodnan Skin Score (mRSS). Higher mRSS scores indicate more severe skin involvement.

Other efficacy measures include lung involvement, evaluated by high-resolution CT scans and by assessing forced vital capacity (a measure of lung function), and physical function analyzed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI is a self-assessment tool to measure functional ability in activities of daily living.

It will also determine tibulizumab’s efficacy using the revised Combined Response Index in Systemic Sclerosis, a composite outcome measure that includes mRSS, FVC, HAQ-DI, and patient and clinician global assessments.

The company also plans a Phase 2 trial in people with hidradenitis suppurativa, another inflammatory skin disease.