Market Overview

180 Therapeutics Announces Positive Results from a Phase 2a Clinical Trial of Anti-TNF Therapy in Dupuytren's Disease

Share:

--- Potential New Treatment Option for a Severe and Disabling
Inflammatory Hand Disease ---

180
Therapeutics LP
, a clinical stage biopharmaceutical company focused
on the discovery and development of novel biologic therapies for the
treatment of fibrosis, a process of excessive undesirable scarring which
is a major unmet medical need in many different human diseases, today
announced positive results from a Phase 2a clinical trial of the
anti-TNF monoclonal antibody, adalimumab, in patients suffering from
Dupuytren's disease. The results were published
in the journal EBioMedicine, published by The Lancet.

Research by the scientific founders of 180 Therapeutics, Professors Sir
Marc Feldmann and Jagdeep Nanchahal, MD, PhD uncovered the role of tumor
necrosis factor (TNF) in driving the development and activity of
myofibroblasts, the cells responsible for the fibrosis that cause the
fingers of patients with Dupuytren's disease to curl irreversibly into
the palm.

The Phase 2a clinical trial was conducted by researchers at the Kennedy
Institute, Nuffield Department of Orthopaedics, Rheumatology and
Musculoskeletal Sciences, University of Oxford, UK, working with
clinicians at NHS Lothian, Scotland. The dose ranging study found that
injection of the anti-TNF drug, adalimumab, into Dupuytren's disease
nodules results in the reduction of key cellular markers of fibrosis.
The study was supported by the Wellcome Trust, UK Department of Health
and 180 Therapeutics. Based on these clinical Phase 2a findings, the
company, together with the Wellcome Trust and Department of Health, is
now supporting a Phase 2b clinical trial of adalimumab injected directly
into the fibrotic nodules of patients with early stage Dupuytren's
disease, which will assess efficacy to retard disease progression over
18 months.

"Our study has demonstrated that the anti-TNF drug, adalimumab, injected
directly into the diseased tissue of patients may be effective in
targeting the pro-fibrotic myofibroblast cells responsible for
Dupuytren's disease," said Jagdeep Nanchahal, MD, PhD, University of
Oxford Professor of Hand, Plastic and Reconstructive Surgery, who led
the study. "This brings new hope to people who suffer from this common
disabling condition, with its frequent recurrences, who currently have
few treatment options other than surgery or collagenase for late stage
disease."

"Based on results so far we are very optimistic about the likelihood of
clinical efficacy in our ongoing Dupuytren's Phase 2b clinical study.
This is because our approach has been based on investigating human
diseased tissue in the lab, the same approach which provided the
rationale for the translational path we pioneered in rheumatoid
arthritis which showed the first dramatic clinical benefit of anti-TNF
in patients afflicted with rheumatoid arthritis," said Professor Sir
Marc Feldmann, co-founder of 180 Therapeutics and a Lasker Award winner.

About the Phase 2a Trial
The randomized, dose response,
placebo-controlled Phase 2a trial recruited 28 patients with Dupuytren's
disease who were scheduled to receive elective surgery to remove
diseased tissue from their hands. Two weeks prior to surgery, patients
received a single injection of the anti-TNF drug, adalimumab, at various
dose levels, or placebo. The tissue removed during surgery was then
analyzed in the laboratory. Adalimumab, at a dose of 40mg, reduced
expression of the fibrotic markers, α-smooth muscle actin (α-SMA) and
type I procollagen proteins, at 2 weeks post injection, suggesting
anti-TNF therapy may have utility in treating early Dupuytren's disease
by preventing activity of disease causing myofibroblast cells. The
treatment was found to be well-tolerated. The Phase 2a study publication
is available on line in the journal EBioMedicine, published by The
Lancet
: https://www.ebiomedicine.com/article/S2352-3964(18)30229-9/fulltext

About Dupuytren's Disease
Dupuytren's disease is a common
fibrotic condition of the hand that causes the fingers to curl
irreversibly into the palm, leading to discomfort, pain and loss of hand
function. In severe cases, digit amputation may be necessary. The
disease affects approximately 4% of the population of Western Europe and
the USA. Pharmaceutical treatments are extremely limited and there are
no approved treatments for preventing progression of the disease.

About 180 Therapeutics
180 Therapeutics' is a clinical-stage
company with a unique scientific approach and therapeutic drug pipeline
for fibrosis, based on the ground-breaking science pioneered by Sir Marc
Feldmann, a prestigious Lasker Award recipient for his work which led to
the discovery of the utility of anti-TNF therapeutics. The discovery of
TNF as a mediator of numerous immune mediated diseases, originated from
the unique approach of analyzing human disease tissue from patients with
rheumatoid arthritis, to identify the key mediators of disease. This
approach has been used again for the analysis of human Dupuytren's
disease tissue from patients with active fibrosis to identify a novel
therapeutic target. Our areas of interest include fibrosis of the liver
(NASH) and the musculoskeletal system, including Dupuytren's disease. http://www.180therapeutics.com/

View Comments and Join the Discussion!