An experimental drug known as LOU064, an inhibitor of the Burton Tyrosine Kinase (BTK) protein, according to Novartis-funded research, can reduce the activation of B-cells in both lab dishes and in animal models pointing to therapeutic potential to fight diseases such as Sjögren’s syndrome, according to recent research results.

What is Sjögren’s Syndrome?

This autoimmune disease affects the entire body as it attacks its own tissue, with symptoms including extensive dryness and potentially serious complications such as profound fatigue, chronic pain, major organ involvement, neuropathies, and lymphomas. According to the Sjögren’s Syndrome Foundation, as many as 4 million in America alone suffer from this autoimmune disease—90% are women. About half of the disease comes alone, and another half occurs in the presence of another autoimmune disease such as rheumatoid arthritis or lupus. The disease was first identified in 1933 by Dr. Henrik Sjögren. Since then, it has proven to affect virtually every racial and ethnic group. Although general awareness of this disease among the public is low, increased professional awareness is needed to expedite new diagnoses and treatment options. The disease is driven to some extent by abnormal activity of B-cells—the cells responsible for generating antibodies. 

Research to Date

Early-stage industry-sponsored research was recently confirmed by healthy volunteers, reports Sjögren’s Syndrome News’ Marisa Wexler, MS. Thus far, the early-stage investigational drug evidences that it is well-tolerated, demonstrating a promising safety profile. Recent results, reports Ms. Wexler, were shared at the 2019 American College of Rheumatology/Association of Rheumatology Professionals in Annual Meeting held in Atlanta, Georgia in a poster titled “LOU064: A Highly Selective and Potent Covalent Oral BTK Inhibitor with Promising Pharmacodynamic Efficacy on B Cells for Sjöegren’s Syndrome.” Phase II clinical trials are ongoing.

During preclinical research, Sjögren’s Syndrome News’ Wexler reports that investigators found that in cell-cultured in dishes, the investigational drug effectively impeded BTK activity in both B-cells and basophils (another type of immune cell with relevance to the disease). Moreover, the therapy appears to be optimized to block BTK as the preclinical investigators found it is more effective against BTK than 456 other tested proteins. With female rats, the drug reduced IgM antibody production. IgM can be produced at high levels in some of Sjögren’s syndrome patients. Interestingly, Wexler reports that when studied in a rat model of arthritis, a comparable dose of LOU064 “induced fast and complete reduction of paw swelling and inhibited histological bone/cartilage erosion and inflammatory infiltrates”.

Moreover, in a Phase I safety study using human volunteers, the drug produced a positive safety profile up to 600 mg with no serious adverse events reported. Of note, the B-cell production of an activation marker (CD69) was cut by half at doses of 30 mg or greater after 24 hours.

The Investigational Drug; LOU064

LOU064 is an inhibitor of the Burton Tyrosine Kinase (BTK) protein, which can reduce the activation of B-cells in both lab dishes and in animal models, pointing to the therapeutic potential to fight diseases such as Sjögren’s syndrome, according to recent research results. As the body’s immune system attacks its own tissue, driven at least in part by abnormal activity of B-cells, reports Ms. Wexler, the actual inhibition of these cells represents a potential strategy for treating the disease. A protein expressed only by certain types of immune cells, such as B-cells, BTK plays a critical role in maturation, and activation and comparable inhibitors already approved and prescribed for certain B-cell lymphomas include Imbruvica (ibrutinib), Burkina (zanubrutinib), or Calquence (acalabrutinib).

The Current Clinical Trial: LOUiSSE

A current Phase II study called LOUiSSe is evaluating the safety and efficacy of LOU064 in patients with moderate to severe Sjögren’s Syndrome. Targeting 252 patients, this is an adaptive, randomized, double-blind, placebo-controlled multi-center trial. A triple masking study (e.g., participant, investigator, and outcomes assessor), study sites are in Europe (Germany, Hungary, Switzerland, and Spain) and Australia (Tasmania). The study commenced this past summer and concludes in January 2023. Novartis is still in need of patients to enroll.

Call to Action: Sign up for TrialSite News Daily Newsletters for material updates ongoing. Novartis doesn’t publicly disclose its principal investigators or sites in ClinicalTrials.gov. A key research lead for Novartis’s LOU064 is Bruno Cenni, immunology research group leader.

Source: Sjogrens Syndrome News

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