Bimekizumab vs. Risankizumab: BE BOLD Study Insights with Jeff Stark

In a recent interview with Dermatology Times, Jeff Stark, MD, vice president and head of immunology at UCB, shared insights into the BE BOLD study, which aims to directly compare bimekizumab with the IL-23 inhibitor risankizumab in treating psoriatic arthritis. This study addresses the critical need for head-to-head data that can guide treatment decisions for both dermatology and rheumatology practitioners. Drawing on his extensive clinical experience and a decade at UCB, Stark highlighted the importance of evaluating therapies through elevated endpoints, with a particular emphasis on joint health in conjunction with skin responses.

TRANSCRIPT

Jeff Stark: Thank you for the invitation to join you. My name is Jeff Stark. I lead the medical affairs team at UCB in immunology, including our areas of therapeutic focus in both dermatology and rheumatology. I've been with UCB for about the last 10 years, and I'm a rheumatologist by training and previously in full time clinical practice.

Dermatology Times: Can you give an overview of the study design and timeline of BE BOLD?

Stark: We’re excited to share the news of the BE BOLD study with the community across both dermatology and rheumatology, recognizing that the disease state of psoriatic arthritis is equally important to both therapeutic communities. This will be the first study for the bimekizumab clinical program in the area of psoriatic arthritis that directly compares 2 active therapies in a head-to-head fashion powered for superiority. The bimekizumab clinical program has already been quite robust in this regard, in the area of dermatology, where we've had head-to-head studies that have demonstrated the superiority of bimekizumab versus 3 active comparators, including adalimumab, secukinumab and ustakinamab. Those represent, of course, 3 therapeutic approaches to treatment that are available for the treatment of psoriasis, but has not included, to this point in time, the head-to-head versus the mechanism of action of interleukin (IL)-23 inhibition. BE BOLD will add to that body of head-to-head evidence that exists for bimekizumab by now including a study that directly compares bimekizumab with the IL-23 inhibitor, risankizumab. We're very excited about the study for several reasons. The first is that clinicians care very much about head-to-head studies in the sense that it informs their treatment choices. It helps clinicians who are selecting, across the many mechanisms of action of therapy, the ability to choose the 1 that has the greatest likelihood of benefiting their patients that they're taking care of. So we're very excited about the opportunity to bring this study forward in the hopes that it will inform those treatment choices for the dermatology and rheumatology communities who are taking care of psoriatic arthritis patients today. The study will include on-labeled doses for both medications, so approved doses in psoriatic arthritis for both bimekizumab and risankizumab, and we'll compare those 2 therapies according to a primary endpoint of ACR50 assessed at 16 weeks. We think this is very important, not only because it will add to the body of evidence that's in existence for bimekizumab, but it will also help to add to the body of evidence for head-to-head studies in psoriatic arthritis in general. We know there have been several previous head-to-head studies, but those have perhaps not met the expectations of the clinical community in 1 way or another. Either, the study did not focus specifically on joints, but maybe used a composite endpoint that blended skin and joints together. Some of these studies, frankly, just did not meet the primary endpoint, or only met it for an off-label dosage of the medication that was being studied. We're very hopeful that by looking at on-label doses of both medications, bimekizumab and risankizumab, that we will have the ability to provide meaningful data that actually helps to inform patient care.

DT: How were the endpoints of this study chosen and how do they compare to similar studies?

Stark: I think that these are important questions in how we design a study and help to set up that study to meet the real needs of the clinical and patient communities. In the area of psoriatic arthritis, joints are very important, not just to the rheumatologist, but to the dermatologist as well. We know that in psoriatic arthritis, if joints are not adequately controlled, if we don't reduce inflammation significantly in the joints, then permanent and irreversible joint damage can and does ensue. Designing a study for which the primary endpoint is joint health is a very important aspect of this study, and certainly was part of our consideration in choosing that primary endpoint. Moreover, we also have chosen an elevated joint endpoint, not the traditional ACR20 score that most people are accustomed to see in psoriatic arthritis trials, but rather an ACR50. I will say that this is in keeping with elevated endpoints that we have chosen throughout the bimekizumab clinical program, whether that be in psoriasis, psoriatic arthritis, or axial spondyloarthritis, we've chosen more elevated primary endpoints in all of those studies. The reason for that is we know that patients deserve more than a 20% improvement. Patients really need to and aim to achieve the highest level of inflammatory control that they can in the interest of controlling their disease, improving their symptoms, but very importantly, preventing those long term consequences of uncontrolled inflammation that we know can damage the quality of life and well being of patients with psoriatic arthritis. I will say that skin is not unimportant. Although joints are often paramount in our thinking, and 1 of those areas that we really want to go to great efforts to protect for the patient, skin is also very important to the quality of life of patients, and so we certainly are assessing skin responses in the course of this study. We do have a secondary endpoint of PASI100 responses, again, a very elevated endpoint reflecting not just improvement in the skin, but complete resolution of skin psoriasis. We know ultimately, that's what patients want and what they deserve. We're certainly not ignoring skin in the study, but recognize that in a multi-domain disease like psoriatic arthritis that affects multiple organ systems, it's important to demonstrate that a therapy can significantly improve the patient experience across all of those domains.

DT: How did last month's FDA approval of bimekizumab for psoriatic arthritis impact the research timeline?

Stark: This has been a study that has long been in the works. For 1 thing, it’s a complement to the other, head-to-head studies. By looking at bimekizumab against another mechanism of action of treatment that hasn't been looked at previously, it will add a head-to-head study in psoriatic arthritis, whereas our head-to-head data primarily have been in the area of plaque psoriasis previously. It's a nice complement there. I will say there are a couple other reasons for us to choose to do this study. One is that risankizmab is really the most commonly prescribed IL-23. We know that it's a therapy that is used very commonly, and so the ability to compare a new therapy to a therapy that is used very commonly, we think, provides the greatest likelihood of generating data that will actually be helpful to the community to make choices between therapies. The other reason, though, I will say, is a mechanistic one. We have done quite a bit of preclinical and mechanistic work in the lab at UCB, and some of those studies, along with data from outside of UCB, have shown that while IL-23 is an important cytokine that leads to the production of cytokines like IL-17A and F, there are also IL-23 independent mechanisms of IL-17A and F production. What that means is that by shutting off IL-23 with a powerful inhibitor of that cytokine, you don't address all of the downstream IL-17A and F that are driving psoriatic disease in the joints and in the skin. We think that there is actually a very strong mechanistic hypothesis and a reason for us to expect, and therefore design a study that demonstrates the superiority of Bimzelx or bimekizumab over risankizumab.

DT: What aspect of the study are you most excited to see the results of?

Stark: I think I'm most excited to see results that we hope and have, I think, a strong rationale to hypothesize we'll demonstrate the superiority of 1 drug over another, and those data will be very meaningful to the clinical community to help them choose between all of the various mechanisms of action of therapy that are available to them today. The mechanism of actioniscertainly, for me as a rheumatologist and a scientist, 1 of the things that I think is most intriguing. It’s been very exciting over the last several years, as we have understood more and more about the immune system and how it goes awry in psoriatic disease, the cytokines that are playing a role, they are driving the inflammation, they are causing the symptoms and therefore become targets for treatment. Certainly at UCB, we have built upon what was known about IL-17 a as a driver of inflammation, and also identified IL17F as an important contributor. Now we’ve generated and are now marketing the first molecule that can target specifically both IL-17A and F in an effort to provide greater control of that inflammation.The science is, I think, certainly very elegant. It's very intriguing to those of us who enjoy immunology, but I think ultimately it also underpins the rationale for this study and why we think there is value in investigating these 2 therapies in the area of psoriatic arthritis.

DT: How does this study fit into the current research climate?

Stark: There is a great desire for head-to-head data. The days of comparing new therapies against placebo alone, I think, are certainly past us.When new therapies were coming and there weren't quality existing therapies just to demonstrate that any given treatment was better than placebo was sufficient. We're now in an era where there are multiple robust therapies that are available to the dermatology or rheumatology clinician, and among which they are able to choose. In this climate head-to-head, data becomes extremely important as the clinician is faced with this variety of choices and is attempting to choose the one that is best for the individual patient, and that also gives that patient the highest likelihood of response. In the context of the head-to-head data we've already built in the area of psoriasis, I'm very excited about adding this to that larger body of work, and again, hoping to provide the most informed treatment choices that give patients the highest likelihood of success in seeking treatment.

[This transcript has been edited for clarity.]