Investing in Long-Term Studies May Provide a Better Picture of Cell Therapy Efficacy


Adrian Kilcoyne, MD, MPH, MBA, the chief medical officer of Celularity, discussed what the company learned from relitigating results of legacy trials for a mesenchymal stem cell therapy in Crohn disease.

Adrian Kilcoyne, MD, MPH, MBA, the chief medical officer of Celularity

Adrian Kilcoyne, MD, MPH, MBA

This is the second part of a Q&A with Adrian Kilcoyne, MD, MPH, MBA. For the first part, click here.

Some time ago, Celularity evaluated a mesenchymal stem cell (MSC) therapy for the treatment of Crohn disease (CD) in several phase 1 clinical trials. Although the results of these studies, which measured efficacy outcomes after just a few months, showed promise, they left room for improvement. More recently, the company performed a new analysis on blood samples from the patients treated in these trials and made a surprising finding: at 2 years posttreatment, 50% of the patients had achieved clinical remission. Adrian Kilcoyne, MD, MPH, MBA, the chief medical officer of Celularity, presented the findings of this new analysis at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16 to 20, in Los Angeles, California, in a talk called “Placental-derived mesenchymal-like adherent stromal cell (MLASC) therapy results in alterations in gene and protein signatures associated with inflammation and fistula formation in patients with Crohn’s disease.”

CGTLive™ spoke with Kilcoyne after the conference to learn more about the new analysis and the main takeaways for the healthcare community. Kilcoyne stated his view that even though long-term clinical trials are more expensive and time-consuming, they may be necessary to demonstrate the full effectiveness of some types of cell therapies. He also emphasized the need for the healthcare community to readjust expectations for remission rates as the cell therapy field grows beyond its initial foray with chimeric antigen receptor T-cell (CAR-T) therapies in hematological malignancies.

CGTLive: What would you say are the big implications that the healthcare community should take away from the findings that you presented?

Adrian Kilcoyne, MD, MPH, MBA: I think the key is that when we understand the pathophysiology of fistula formation, which is epithelial to mesenchymal transition—is there a way we can really impact that? Is there a way that we can stop that process, but also go towards repair? We think that the community now needs to think about curing fistulae not necessarily surgically, but importantly, preventing progression to fistulae. We also think it gives the healthcare community an additional tool. I want to be very clear, the biologic products that are available are exceptionally good. However, we also know that almost all the therapies you have thus far stop working at some point in time. This longevity of response we've seen with MSCs after a single treatment course—it's just 2 doses a week apart; this is not extensive treatment—without any further treatment and without any form of maintenance we saw a 50% 2-year clinical remission rate. I think this will give hope that we can give a treatment to patients that can give you duration of effect without the need for ongoing maintenance. Obviously, we need more data to support what I'm saying, but this is 2 potential upsides. Adherence could be a lot better if we were able to give 1 treatment course and enable patients to get to a longer-term remission. That's great, but the cost implications are also huge for the healthcare economy in terms of not having the requirement of maintenance therapy.

As we progress forward, we’d love to start looking at the markers in this piece of work and determine whether or not with time we would need to redose these patients. So there's [still] a number of unanswered questions, but nonetheless I think it gives real hope that if we investigate further it may be a much more patient-friendly and financially less toxic approach to the management of CD.

The real learning for us is this: Let's be really careful in how we design our clinical trials and how we choose our patients because if we get the timing of the endpoints wrong we're going to fail to show the benefit. Let's be willing to invest the extra to follow the patients for the right amount of time. Yes, it will be more expensive; yes, there may be some delay to getting our end point if we're looking at a 6 month to 1 year end point rather than a 12 week end point. But I think that's when you're really gonna start seeing the benefits for patients. So it's really a learning for us in understanding the pathophysiology of the disease and the mode of action of the MLASCs in this particular space.

Is there anything else you’d like to share with the audience?

As we move forward, we've seen it across all of cell therapy. We were spoiled a little in the T-cell therapy space. We came out with CAR-Ts, we've seen exceptional results. We've seen exceptional results in acute lymphocytic leukemia, in diffuse large B-cell lymphoma, we've seen complete remission rates in reach of 60%—and even those data seem to hold true in the real world—so we've seen exceptional results. Following that, cell therapy gets a little bit more difficult. We've seen that in the solid tumor space, we've seen it with natural killer cells—that everyone expects a 60% remission rate. The low hanging fruit may well have been picked now. We know that in order to get optimal impact—and we know it from the studies we've done—that we may have to do more.

That's why we are not looking at taking this exact MLASC construct with us to market; we're looking at a next-generation construct. We're looking at our learnings and saying, ‘How do we edit these [cells] to make them an awful lot better?’ And that's what we're doing right now. When we take this to clinical trials, it'll be next-generation with some sort of editing technology—certainly tissue factor knockout to improve the tolerability and any sort of side effects, but we’re also really thinking about how we target it exactly to where we want it to be. I can't go into huge details on this, but it will be a next-generation product to boost efficacy, to boost persistence, and to boost tolerability for patients. We hope that it could potentially be somewhat disruptive in the field of CD and we also think there's some other therapeutic areas where this would add a critical benefit.

Transcript edited for clarity.

Click here for more coverage of ASGCT 2023.

Kilcoyne A, Koppisetti S, GloverB, et al. Placental-derived mesenchymal-like adherent stromal cell (MLASC) therapy results in alterations in gene and protein signatures associated with inflammation and fistula formation in patients with Crohn’s disease. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #1111
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