180 Life Sciences Corp. in collaboration with the University of Oxford, announced final results from its Phase 2b study in patients with Dupuytren's disease. The positive data results were published in The LancetRheumatology.

Fibrosis of the hand, known as Dupuytren's disease, is a common chronic, progressive condition that causes the fingers to curl irreversibly into the palm and can be very disabling. Approximately 20-35% of patients with a palmar nodule progress to finger contractures. Roughly 12 million patients in the U.S., 2.5 million in the U.K. and 22 million in the EU have Dupuytren's disease.

Currently, there is no approved treatment for early-stage disease and patients must wait until the disease progresses with loss of hand function before undergoing surgery or treatment with collagenase. Unfortunately, the disease tends to recur after these treatments. The Phase 2b trial was designed as a randomized, double-blind, placebo-controlled study to assess the efficacy of local injection of anti-TNF treatment, adalimumab, in participants with early-stage Dupuytren's disease and was led by Professor Jagdeep Nanchahal, clinician-scientist at the University of Oxford and Chairman of the Clinical Advisory Board at 180 Life Sciences who said: “This trial represents the clinical translation of laboratory findings where identified of TNF as a therapeutic target2,3, and the Phase 2a dose ranging clinical trial to identify the optimal dose and formulation4 effective in downregulating myofibroblasts.” The trial recruited 140 patients from two sites in the U.K. Patients were randomized 1:1 to the treatment arm or placebo.

Patients in the treatment arm received four injections of 40mg adalimumab in 0.4ml at baseline, which was determined to be most efficacious in the earlier Phase 2a study, at three, six and nine months. Patients were followed up at 12 and 18 months. Eligibility criteria included adults with early-stage Dupuytren's disease and a clinically distinct nodule with a clear history of progression in the preceding six months.

The trial was funded by the Health Innovation Challenge Fund (Wellcome Trust, Department of Health and Social Care) and 180 Life Sciences, and sponsored by the University of Oxford. The primary endpoint from the Phase 2b trial was nodule hardness at 12 months measured with a durometer. Nodule size, a key secondary endpoint, was measured using an ultrasound scan at 12 and 18 months.

Key findings of the study were: Nodule hardness was lower in the anti-TNF treatment arm compared to placebo (-4.6AU; 95% CI -7.1 to -2.2; p=<0.0002) at 12 months and decreased further at 18 months (-5.8AU; 95% CI -8.7 to -3.0; p=<0.0001), 9 months after the last injection. Nodule size (area), measured using ultrasound scan, was also lower in the anti-TNF treatment arm compared to placebo at 12 months (-8.4mm2; 95% CI -13.8 to -2.9; p=<0.0025), and decreased further at 18 months (-14.4mm2; 95% CI -19.9 to -9.0; p=<0.0001). There were no treatment-related serious adverse events in the trial.

Patient compliance was high, with 84% returning for all 4 injections. Fewer patients in the treatment group underwent or were awaiting surgery compared to placebo at 18 months. However, the overall numbers were small and longer-term follow up would be required to confirm this.

In conclusion, the data showed that in patients receiving anti-TNF treatment, nodules continued to soften and regress at the 18-month follow up, which was nine months after the final dose. These results suggest that treatment of early-stage Dupuytren's disease with adalimumab can have a profound local biological effect and potentially provide a much-needed early therapeutic option for patients with a chronic, debilitating disease.