Esbriet (pirfenidone) is an antifibrotic treatment developed by Genentech and used to treat idiopathic pulmonary fibrosis (IPF). It is currently being tested in patients with scleroderma where IPF is a possible complication.

Scleroderma is an autoimmune disorder where the patient’s own immune system overreacts and mistakenly attacks healthy tissues in the body. It is a complex disorder that has multiple manifestations and can affect many tissues and organs. The hallmark of scleroderma, however, is thick and hardened skin, which is linked to an excessive production of collagen protein and the formation of scar tissue. This scar tissue can also form in other organs including the lungs, heart, kidneys, and stomach, and lead to complications such as pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD) characterized by the progressive scarring of the lung tissue. The most common type of ILD is IPF that can be treated with antifibrotic medications like Esbriet.

How Esbriet works

Scleroderma can cause scar tissue to form deep within the lungs. This scar tissue thickens and becomes stiff with time, making it harder for the lungs to work properly. Decreased lung function can lead to other problems due to other organs and tissues not receiving enough oxygen.

Esbriet belongs to a class of medicines known as pyridones. It works by inhibiting the synthesis of TGF-beta, a chemical mediator that plays a key role in fibrosis. It also inhibits the synthesis of TNF-alpha, a cell signaling molecule that promotes inflammation. Esbriet can, therefore, delay the formation of the scar tissue and slow the progression of IPF, but it is not a cure for the disease.

Esbriet in clinical trials for scleroderma

The safety and tolerability of Esbriet in patients with scleroderma-associated ILD were assessed in an open-label Phase 2 clinical trial (NCT01933334) called LOTUSS. The findings, published in The Journal of Rheumatology, demonstrated that although an overwhelming majority of patients experienced treatment-associated side effects, the tolerability of the treatment was acceptable. These side effects included nausea, vomiting, loss of appetite, diarrhea, headache, dizziness, a feeling of tiredness, weight loss, cold symptoms (such as a stuffy nose, sneezing, and a sore throat), insomnia, joint pain, and abnormal liver functions.

A randomized, placebo-controlled Phase 2/3 clinical trial (NCT03068234) will further investigate the safety as well as the effectiveness of Esbriet in patients with systemic scleroderma. Researchers will analyze the effect of the treatment on lung fibrosis and digital ulcer formation. The trial aims to recruit 72 patients, but is not yet open for recruitment.

Another randomized, placebo-controlled Phase 2 clinical trial (NCT03221257) aims to study the effect of combining Esbriet with CellCept (mycophenolate mofetil) an anti-inflammatory and immunosuppressive agent, on scleroderma-related interstitial lung disease. This study is currently recruiting approximately 150 participants at sites in California and Michigan.

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