What's New? Upcoming Research on Fibrosis

This year, SRUK are excited to begin 2022 by looking ahead, to see what exciting research funded by SRUK and other organisations is on the horizon. In this series of articles, we will explore the upcoming research, from existing projects which have been running throughout 2021 and are soon to publish their results, to brand new projects which are kicking off in 2022.

The first instalment of this new series looks at upcoming research focusing on fibrosis, one of the three hallmarks of scleroderma.

Fibrosis

Fibrosis is the name given to the development of fibrous connective tissue, which typically occurs as a healthy response to injury or damage. In people with scleroderma excessive fibrosis leads to excess collagen building up in connective tissues, affecting multiple organs within the body. This excess tissue causes scarring, bringing about structural change, which, with time, can impair organ function.

As a person’s organs thicken, they can experience many symptoms, the exact nature of which depend on the organ(s) affected. For example, fibrosis in the lungs can causes shortness of breath and challenges in breathing. If the skin on a person’s body thickens they may experience reduce mobility and dexterity of their hands. Regardless of which organ(s) are affected, fibrosis significantly reduces the quality of life for someone with scleroderma.

Excessive fibrosis is a major driver of scleroderma, which eventually leads to irreversible organ damage  it presents an attractive therapeutic target within scleroderma. Nintedanib, recently approved for the treatment of progressive fibrosing interstitial lung disease works by blocking fibrotic pathways. To bring a treatment to market it has to move from investigational laboratory work, through the preclinical research pathway, and be successful in four phases of clinical trials. This article focuses on two different research projects which span that journey. 

1.Phase 2 Clinical Trial of Anti-Fibrotic Drug PRA023

The first project of 2022 we are excited to tell you all about is a phase 2 clinical trial for an anti-fibrotic and anti-inflammatory medicine called PRA023.

PRA023, developed by US-based biotech Prometheus Biosciences. is a monoclonal antibody-based drug. Monoclonal antibody treatments have become a household name since this type of technology has been used to develop several treatments for severe COVID-19 infection.  PRA023 targets a molecule called cytokine TL1A, important in inflammatory responses and fibrosis. Patients with scleroderma have elevated levels of TL1A in their blood and this molecule has been shown to drive lung fibrosis in animal models of the condition, and has been shown to play a role in the progression of scleroderma.  PRA023, is being tested in phase 2 clinical trials of both the inflammatory bowel disease, Crohn’s disease, and in patients with ulcerative colitis.

An additional phase 2 clinical trial for people with scleroderma is anticipated to start recruiting in the first half of 2022. In this trial the efficacy of PRA023 in 100 individuals with scleroderma associated interstitial lung disease (SSc-ILD) over a period of 50 weeks, the study will evaluate the effects of treatment on lung capacity. They will assess how PRA023 impacts the forced vital capacity of someone with SSc-ILD, e.g. how much air can be forcibly exhaled following a deep inhalation.

Results from the Crohn’s and ulcerative colitis trials should are anticipated by the end of 2022, which the findings from the scleroderma study expected in 2023, when the year-long trial concludes. The findings will determine whether PRA023 can enter Phase 3 trials which should give more patients the opportunity to participate and try this new treatment and potentially lead to another weapon in the armoury against SSc-ILD.

Reference: PRA023 for Ulcerative Colitis, Crohn's Disease & SSc-ILD (prometheusbiosciences.com)
Recruiting sites: Not yet listed, it is anticipated to be USA only

2.  IL-11 Therapies - Development of Anti-Fibrotic and Anti-Inflammatory Therapies

In September 2020, Boehringer Ingelheim, a global pharmaceutical company with an interest in scleroderma and other fibrosing conditions, announced their partnership with biotechnology company Enleofen. Enleofen, a small Singapore-based start-up company was investigating the potential of targeting Interleukin 11 (IL-11) as a way of halting and even reversing inflammation and fibrosis to restore organ function. Using their portfolio of therapeutic molecules, Enleofen had made some compelling findings in their pre-clinical studies using mice models of the disease which demonstrated the potential of this therapeutic approach.

Under the partnership the companies will develop a range of antibody-based ‘first-in-class anti-IL-11 therapies for a range of fibrotic diseases.’ The eventual hope is that these molecules will enter clinical trials in patients with scleroderma and other conditions. As testament to the therapeutic potential of blocking fibrosis in scleroderma and multiple other conditions, this deal may see Enleofen receiving payments in excess of $1 billion per product - a sizeable investment for what has been a pre-clinical programme of work.

It is clear that fibrosis is a complicated process, with many molecules being involved in driving this response. The more ways which can be developed to interfere with fibrosis the better since this will open up more treatment options to patients and potentially allow for combination therapy. Caution should be applied to the findings in animal models that this molecule can reverse fibrosis, since this might not translate to established fibrosis in humans but nonetheless this work is undoubtedly very exciting. Let’s hope that the next news that we hear will be the announcement of a clinical trial!  

Reference: Fibrotic diseases partnership with Enleofen | Boehringer Ingelheim (boehringer-ingelheim.com)

The SRUK Research Team hopes that 2022 will see an end to the effects that the pandemic has had on research and that new and ongoing projects will further our understanding of the biomechanisms behind scleroderma and provide more insight into new treatments for the condition(s).

As these amazing projects begin to publish their results, SRUK will make sure to keep you informed – keep an eye on our Research News page for all the latest articles.