Phase II Trial for Gilead’s IPF Therapy Simtuzumab Terminated After DMC Recommendation


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IPF and fibrotic diseases

Gilead Sciences, Inc. recently announced in a press release that it is stopping its RAINIER Phase II clinical trial testing the investigational monoclonal antibody simtuzumab in patients with idiopathic pulmonary fibrosis (IPF), noting that the experimental therapy did not demonstrate efficacy in treating the disease.

Simtuzumab is a humanized monoclonal antibody with immunomodulatory properties. The antibody works by binding to the cysteine rich domain 4 (SRCR4), which is known as a “scavenger receptor” located on the enzyme lysil oxidase-like 2 (LOXL2). By binding to this receptor, the therapy blocks its ability to recruit fibroblasts, and ultimately leads to an inhibition of the synthesis of growth factors and chemokines, cell growth, differentiation, and proliferation. LOXL2 is essential for the synthesis of connective tissues, and its blockade prevents the excessive formation of connective tissue and consequent fibrosis — hallmarks of IPF.

Phase II trials are usually designed to determine the best drug dose to administer, as well as a drug’s safety profile and efficacy in small groups of patients. In this case, the Data Monitoring Committee (DMC) recommended the termination of the Phase II  RAINIER study after an analysis revealed that the clinical trial showed lack of efficacy for simtuzumab. Gilead Sciences also reviewed the data and reached a similar final conclusion, namely that the study did not show enough evidence of any treatment benefits in the group of IPF patients receiving simtuzumab treatment.

Gilead Sciences will, however, continue to assess simtuzumab as a therapy for other conditions, more specifically through its Phase II trial of simtuzumab in patients with non-alcoholic steatohepatitis (NASH) and Phase II trial of simtuzumab in primary sclerosing cholangitis (PSC). The DMC of both studies have recommended their continuation, and both studies have a 96-week endpoint.

Gilead Sciences is a biopharma company that discovers, develops and commercializes novel therapeutics in areas of unmet medical needs in diseases such as IPF, where more therapeutic options are still needed.

IPF is a progressive, potentially fatal lung disease, in which the alveoli and lung tissue are damaged and become scarred and think (a process called “fibrosis”). The condition may lead to severe breathing difficulties, compromising oxygen transfer between the lungs and the bloodstream. Sufferers from IPF often report progressive dyspnea, which can ultimately lead to respiratory failure. There is currently no cure for IPF and 128,000 individuals are estimated to suffer from it in the U.S. alone, with approximately 48,000 new cases diagnosed yearly. It is estimated that only one-third of the patients overcome the five-year milestone after being diagnosed.