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James Woody, MD, PhD, explains the key findings of the Phase 2b clinical trial, “Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).”
Rheumatology Network interviewed James Woody, MD, PhD, to understand the key findings of the Phase 2b clinical trial, “Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).” During the study, investigators repurposed adalimumab to treat this disabling condition that causes fingers to curl irreversibly into the palm. Woody is the CEO of 180 Life Sciences.
James Woody, MD, PhD: [Dupuytren’s disease] is one of the inflammatory conditions that goes along with the others, like rheumatoid arthritis, Crohn's disease, and psoriasis. It's just a different kind of indication. And so, what happens is that people begin to form a small nodule in the palm of their hand. And this small nodule creates some chords and it pulls the fingers together. And eventually they become disabled. There's a number of therapies after the condition has become disabling, like injections or surgery, to relieve the finger contractions. My wife had this and had steroid injections for a year that didn't help and she finally had to have corrective surgery. Even then it still kind of comes back. So one option is actually treating patients very early, as soon as we see these nodules forming, to see if we can prevent the disability that eventually develops.
Rheumatology Network: What inspired your team to repurpose adalimumab for treating this condition?
JW: In our scientific studies by Dr Jagdeep Nanchahal at Oxford University, he was able to do a trial where these patients were going to surgery. So, they would inject these nodules with different substances and see which one of them shut off the fibrotic pathways. And he found that the anti-tumor necrosis factor (TNF) worked the best. And the reason we use the adalimumab was that AbbVie made a very concentrated formulation that worked very well for what we needed to because you could only inject a very tiny amount into these nodules in the end. So that's why we chose there's their product. And it also was citrate-free. Citrate causes stinging when you inject these anti-TNF agents. So that was absent, and a high concentration is why he chose to use that particular formulation.
RN: What was the study design that your team used?
JW: For the for the Phase 2b clinical trial, he was able to determine what dose needed to be injected in order to shut off the fibrosis pathway. We knew what dose to give to these patients. And then the larger trial of 140 patients he reported on utilized this injection scheme and gave injections about once every 3 months over a year. And then all of the patients came back for the injections. We looked at them and measured the responses. It was a placebo-controlled trial, so half the patients got the drug and half the patients got saline injection. The end of the trial was to examine these for a whole range of primary and secondary endpoints and all of them were statistically significant. It was a huge benefit and a very novel trial. It was the first one ever run for preventing disease, as opposed to treating it with just a usual course.
RN: What were the primary and secondary endpoints?
JW: The primary endpoint was the size of the nodule and the softness and how far it extended into the into the palm of the hand. There were several kinds of measurements they did to examine this. So basically, the idea was to try to decrease the size of the nodule and the hardness of the nodule so that it didn't go forward to create the fibrous cords.
RN: And what were the results of this study?
JW: The results were that the primary endpoints and the secondary endpoints all were statistically positive. So, for a first trial in a unusual indication, this is very good news.
RN: In your opinion, what is the clinical significance of these results?
JW: Well, I mean, if you had a nodule in your hand, you would probably go to “Dr Google” and see what's going to happen next. And from that, you would be able to learn that eventually this is going to form these fiberous lines and pull your fingers together. You can't type, you can't button your clothes, etc. A whole variety of things that none of us would like to have. When people were aware of this, I think they were pretty motivated that there was a trial to try to prevent this disability from happening altogether.
RN: What are the next steps in your research?
JW: Well, for this particular program, we will be meeting with the regulatory agencies in the US (Food and Drug Administration [FDA]) and in the UK (Medicines and Healthcare products Regulatory Agency [MHRA]) and determine the path forward for making this available to people so that we could get an approved drug and be able to treat people. I think it's pretty desirable for people to prevent this rather than to go through the whole process like my wife did.
RN: Absolutely. Is there anything else that you would like our audience to know before we wrap up?
JW: Well, we have other trials going on in the fibrosis area. The second trial that will be starting probably in first part of next year is called frozen shoulder. That's where the shoulder becomes extremely painful and eventually kind of freezes up. Because it's so painful, and there's fibrosis in it, it turns out that about half of those patients have Dupuytren’s. We think the fibrosis in the shoulder is the same kind of scientific metabolic process. We'll be injecting the anti-TNF into the shoulder and see if we can relieve that from progressing as well. So that's the next trial coming along. And I think, given the success of this first one, and the science that's behind it, we are quite optimistic that one may work as well.