Transcript
Announcer:
Welcome to ReachMD. This medical industry feature is a recording of a live broadcast brought to you by UCB, titled “Expert Perspectives on a Treatment for Plaque Psoriasis.” The expert panelists for this live broadcast are Dr. Andrew Blauvelt, Dr. April Armstrong, and Dr. Bruce Strober.
Dr. Blauvelt:
Hi, I'm Dr. Andy Blauvelt. Thank you for joining us for this live broadcast: Expert Perspectives on a Treatment for Plaque Psoriasis. Today we're talking about the immuno-dermatology pharmaceutical created by UCB. UCB has a long history of creating impactful pharmaceuticals, and now BIMZELX, bimekizumab has arrived!
BIMZELX is a humanized interleukin-17A and F antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Transformative treatment results are based on the results of the BE RADIANT versus secukinumab, BE VIVID versus ustekinumab, and BE SURE versus adalimumab, and BE READY versus placebo clinical trials.
This is a promotional program sponsored by UCB, so the panelists and I have been compensated for presenting the educational information you're about to hear. Joining me to discuss BIMZELX are two well-respected experts in the field of dermatology, Dr. April Armstrong…
Dr. Armstrong:
I’m excited to be here today!
Dr. Blauvelt:
…and Dr. Bruce Strober.
Dr. Strober:
I’m very happy to be a part of this discussion.
Dr. Blauvelt:
Thank you both for being here today to talk about BIMZELX. Reminder for those of you listening in to submit all questions via the Q and A box, and we will address as many as we can at the end of the presentation.
Now look at these numbers showing the global psoriasis impact that BIMZELX has already had. BIMZELX has been extensively studied in clinical trials and those studies have proven its efficacy and safety in adult patients with moderate-to-severe plaque psoriasis. That is why it is already approved by 11 regulatory authorities worldwide and in 40 countries.
One clinician said “The most striking observation, which is supported by the clinical data is the rapid and deep level of response that we see in these patients.” And another clinician commented that his patients have been able to maintain levels of improvement with many actually experiencing complete clearance of their psoriasis.
We're going to discuss how BIMZELX is proven to consistently deliver rapid, complete and sustained clearance for more patients from the very first dose, as measured at Week 4. To start us off, Dr. Armstrong, are there adult patients with moderate-to-severe plaque psoriasis in your practice who may benefit from rapid, complete, and sustained clearance that can be maintained easily?
Dr. Armstrong:
Thanks, Dr. Blauvelt. Yes, I have many patients in my practice who want to see a rapid improvement that can be maintained for years. That's what my patients tell me they want their treatments to do.
This is why I'm so excited about BIMZELX, which delivers rapid, complete, and sustained skin clearance for more patients from the very first dose. And this complete clearance has been maintained for up to about three years in most patients.
BIMZELX has a consistent safety profile in long-term treatment across clinical trials in plaque psoriasis and offers a convenient dosing schedule every 8 weeks after Week 16 with one dose that equals two injections. This is very important to my patients and me.
And UCB is committed to patient access through its BIMZELX Navigate Patient Support program. We'll be talking more about that later in the presentation.
Dr. Blauvelt:
BIMZELX sounds like it comes with a story. Going back to the beginning. Can you give us an overview of the clinical trials for BIMZELX?
Dr. Armstrong:
I'd be happy to. BIMZELX was evaluated in patients with psoriasis across three pivotal Phase 3 trials: BE READY, BE VIVID, and BE SURE. At week 16, BIMZELX exhibited superiority for Psoriasis Area and Severity Index, or PASI, 90 and Investigator’s Global Assessment, or IGA, 0/1 over placebo and ustekinumab in BE VIVID, adalimumab in BE SURE, and placebo in BE READY. Adalimumab is a TNFα inhibitor and USTEKINUMAB is an IL-12/23 inhibitor.
BIMZELX was evaluated in patients with psoriasis in the Phase 3B trial BE RADIANT. At Week 16, BiMZELX exhibited superiority for complete clearance PASI 100, over secukinumab and IL-17A inhibitor.
The clinical trial program included 2,223 patients with psoriasis across the three Phase 3 trials and one Phase 3B trial. Within these clinical trials, 36% of patients were biologic-experienced, some of whom had been on more than one prior biologic, and more than half of these biologic-experienced patients were previously on an IL-17 inhibitor.
Dr. Blauvelt:
Thank you for covering those details so succinctly, Dr. Armstrong. Now, we've heard it mentioned a few times here that BIMZELX is a biologic that selectively targets both IL-17A and IL-17F. Dr. Strober, what does this mean for the treatment of plaque psoriasis?
Dr. Strober:
Thank you, Dr. Blauvelt. BIMZELX is the first and only approved biologic to selectively target those overly expressed IL-17A and IL-17F cytokines in plaque psoriasis.
Dr. Blauvelt:
Along that same line, can you tell us more about targeting IL-17A and IL-17F? In other words, what kind of impact does that have on IL-17–mediated inflammation?
Dr. Strober:
To answer that, let's take a look at this illustration. It depicts the inflammatory pathway in psoriasis, driven by IL-17A and IL-17F production, that can come from both IL-23 dependent and IL-23 independent sources.
So we know both IL-17A and IL-17F are key drivers of inflammation in psoriasis pathogenesis, with IL-17F more abundantly expressed in psoriatic lesions than IL-17A. And if you look at this illustration, you can see different combinations of the IL-17 isoforms from IL-17 dimers: IL-17A/A, IL-17A/F, and IL17F/F.
These dimers bind to the receptor on the surface of keratinocytes signaling the release of othercytokines and chemokines which leads to inflammatory responses of the skin. IL-17A inhibitors interfere with IL-17A/A and IL-17AF. However, they do not intercept with the IL-17F/F dimer.
So, you can see that targeting IL-17A partially interferes with IL-17–mediated inflammation in psoriasis. But only partially.
The mechanism of action of BIMZELX differs from other IL-17A inhibitors. That is because BIMZELX targets both IL-17A and IL-17F, which means it binds to all three IL-17 dimers implicated in psoriasis pathogenesis: IL-17A/A, IL-17A/F, and IL-17F/F. I'll say it again: It binds to all three IL-17 dimers.
This means BIMZELX provides more inhibition of inflammation than inhibition of IL-17A alone. So, BIMZELX interferes with more than one part of the IL-17 pathway.
Dr. Blauvelt:
Thank you for walking us through the mechanism of action, Dr. Strober. If we take a moment to discuss efficacy, Dr. Armstrong, what do you look for to determine a biologic's efficacy?
Dr. Armstrong:
I would say rapid response is one of the most important pieces of efficacy I look for because of how important it is to my patients.
For many of my patients, they may have an important engagement coming up and it's important that they get clear as fast as possible. Also, something in addition to that is that I'm also looking for maintenance and response long term, because psoriasis is a chronic disease, having that long-term maintenance response is very important.
So essentially, when a patient with moderate-to-severe plaque psoriasis walks through my door, I already know how they must be feeling. They're probably feeling very miserable because this disease can really take a toll on the patient's daily life and having that rapid clearance and then being able to sustain and maintain that response is very important to them.
Dr. Blauvelt:
Given the physical toll this disease causes, what is your initial approach to treatment for these patients?
Dr. Armstrong:
When I think about my psoriasis patients that I first meet, I take a very careful clinical history and look at their psoriasis severity and very importantly I also take into account their comorbidities before I choose a therapeutic option for them. And when I consider these treatment options for a patient who's suffering from all these various symptoms that we talked about from psoriasis, I want to help provide relief as quickly as possible. I know that's what they want, it's also what they need from me as their provider.
Dr. Strober:
Now let's go back to the clinical trial results for BIMZELX. Keeping that approach to treatment in mind, Dr. Blauvelt, what can you tell us about the efficacy of this biologic for patients who are hoping to experience rapid relief from their symptoms?
Dr. Blauvelt:
Speaking frankly, I'm excited and impressed that patients across the BIMZELX Phase 3 and Phase 3B trials experience what I would characterize as consistent results across four clinical trials. And that's from the very first dose of BIMZELX. What's more, about 4 out of 10 patients achieved rapid response from the very first dose of BIMZELX at Week 4, as seen in the PASI 90 scores. That is compared to three of the most prescribed biologics, as well as a placebo, in head-to-head trials.
Also, PASI 75 at Week 4, a secondary outcome, was met across the Phase 3 and Phase 3B clinical trials.
Again, BIMZELX delivered rapid response from the very first dose. This is shown by at least 80% mean PASI improvement at Week 4 across clinical trials, where the mean PASI improvement is the average improvement across all participants in any given clinical trial. So in my opinion, BIMZELX is going to be a promising option for patients who want to achieve rapid response from the very first dose.
Dr. Strober:
I agree, and I think rapid response is definitely an important factor to consider here.
Dr. Blauvelt:
Going back to you, Dr. Armstrong, what's another factor that's important to you and your patients when considering efficacy?
Dr. Armstrong:
Returning to something we spoke about earlier, I look for data about how a biologic performs to achieve complete clearance, or PASI 100.
Patients with moderate-to-severe plaque psoriasis are grateful when their psoriasis clears quickly. And once that happens, they want their plaques to go away completely. And this is very important because not seeing any plaques really allow them to feel, I will say in their own words, normal, so that they can really focus on things in their lives that are important to them. So as you can see, PASI 100 is a helpful data point for us because complete clearance is important for our patients.
Dr. Blauvelt:
Dr. Strober, I like to get your thoughts on this as well. Looking at the BIMZLEX clinical trials, what results regarding PASI 100 stood out to you the most?
Dr. Strober:
Well, how much time do I have? Seriously, though, with BIMZELX, the majority of patients—about two-thirds—achieve PASI 100 at Week 16 in each of the Phase 3 trials.
And in a head-to-head trial with secukinumab, which is an IL 17 A inhibitor, 62% of patients on BIMZELX achieved PASI 100 versus just 49% on secukinumab at Week 16. Also, in each of the three Phase 3 and one Phase 3B clinical trials at Week 16, more patients, at least 85%, on BIMZELX achieved PASI 90 versus secukinumab, ustekinumab, adalimumab, and a placebo.
Dr. Blauvelt:
Thanks, Dr. Strober!
In addition to rapid and complete clearance, I want to add that a data point I'd look for in a treatment for my patients with psoriasis is sustained efficacy. Remember, psoriasis is a chronic disease. So, while my patients are delighted when they get a rapid response with their treatment, and they are thrilled with PASI 100, they can get extremely frustrated when a treatment loses efficacy over time. What I look for in a drug is whether the patients who achieve PASI 100 sustain that long-term.
Dr. Strober:
It’s an excellent point, Dr. Blauvelt. On that note, I want to call out two studies with BIMZELX that show complete clearance, PASI 100, and lasting results. In the BE RADIANT trial, patients treated with BIMZELX had a rapid, complete, and sustained clearance up to Week 48. As early as four weeks after the first dose, 14% achieved PASI 100. At Week 16, 62% achieved PASI 100. And at Week 48, 67% achieved PASI 100 versus 46% with an anti–IL-17A.
And if we jumped to the BE SURE pivotal trial, patients treated with BIMZELX achieved complete clearance, PASI 100, and sustained clearance up through Week 56. At Week 56 in the BE SURE clinical trial, 70% of patients in the BIMZELX Q4W/Q8W dosing group achieved PASI 100.
Dr. Blauvelt:
It's important to know that patients achieving PASI 100 at Week 16 maintained complete clearance results from the BE BRIGHT open-label extension, or OLE, trial showed that 82% of Week 16 PASI 100 responders maintained complete clearance, PASI 100, up to approximately three years. Primary objective of the BE BRIGHT OLE was to assess the long-term safety of BIMZELX, and evaluation of efficacy was a secondary variable. All patients in the BIMZELX Q4W/Q8W/Q8W arm achieved PASI 90 upon entering the OLE. Maintenance of the PASI 90 and PASI 100 responses was evaluated through the BE BRIGHT OLE Week 96.
Looking at the pooled analysis from three pivotal Phase 3 studies—BE SURE, BE VIVID, and BE READY—63% of BIMZELX-treated patients achieved PASI 100 at Week 16. Of those patients, 82% maintained complete clearance, or PASI 100, at Week 96 of the OLE trial in the BIMZELX Q8W/Q8W arm, or maintenance/OLE initial dosing group.
So, we've discussed how with BIMZELX patients across the trials achieved a mean PASI improvement of at least 80% at Week 4 from the very first dose. And two-thirds of patients across the trials achieved complete clearance for PASI 100 at Week 16. Additionally, in the BE RADIANT and BE SURE clinical trials, approximately seven out of 10 patients achieved complete clearance, or PASI 100, with BIMZELX after about one year. And in the BE BRIGHT OLE trial, 82% of Week 16 PASI 100 responders maintained complete clearance up to about three years. Just think about that for a second—that's three years of efficacy at approval.
Dr. Strober:
Let's take a look at what rapid, complete, and sustained clearance can look like. In a series of photos from Weeks 0, 4, 16, and 52, you can see the results from the first dose: BIMZELX delivered rapid, complete, and sustained clearance.
The next series of photos shows a patient in one of the trials at Weeks 0, 4, 16, and 48. From these photos, you can see the results from the first dose: BIMZELX delivered rapid, complete, and sustained clearance.
Dr. Blauvelt:
Now that we've covered the efficacy profile of BIMZELX, let's talk about its consistent safety profile. Dr. Armstrong, can you cover what adverse events patients experienced in the trials?
Dr. Armstrong:
Absolutely. Healthcare providers should also note the warnings and precautions for BIMZELX. We'll be talking about them in this presentation, but please also see section five of the full Prescribing Information for BIMZELX. Across our BIMZELX clinical trials, we sought to include a broad patient population reflective of the psoriasis patients you may treat in clinical practice.
Pooled analysis of short-term safety data across three Phase 3 clinical trials included 989 patients with 306 patient-years of treatment with BIMZELX 320 milligrams Q4W. Longer-term safety data across four Phase 3 and four Phase 2 clinical trials included 1,789 patients with 4,245 patient-years of total BIMZELX exposure.
With patients in mind, we designed our safety and laboratory assessments to monitor adverse events of special interest throughout our clinical program. Overall, there were low incidences of adverse events including serious infections, inflammatory bowel disease, adjudicated major adverse cardiovascular events, malignancies, hypersensitivity reactions, and injection site reactions across the pooled analysis of short-term safety data across three Phase3 clinical trials—the BIMZELX Q4W group—and longer-term safety data—the BIMZELX all doses group—across eight Phase 2 and 3 clinical trials.
Notably, long-term safety was measured using exposure-adjusted incidence rate to calculate risk per 100 patient-years. And in the BE RADIANT trial, the percentage of patients with incidences of adverse events of interest in the BIMZELX group was comparable to those in the secukinumab-treated group, except for candidiasis, where incidents was higher in BIMZELX-treated participants.
Dr. Blauvelt:
I want to ask you about one of the adverse events you mentioned. Can you talk more about the incidences of candidiasis during the clinical trials?
Dr. Armstrong:
Yes, let's talk about candidiasis. There was a greater incidence of candidiasis in all BIMZELX-treated groups compared to subjects treated with a placebo. In the pooled analysis of longer-term safety data of all BIMZELX treated groups across eight Phase 2 and 3 clinical trials, greater than 90% of the Candida infections were oral candidiasis.
The vast majority of candidiasis cases were mild to moderate. In fact, the discontinuation rate of BIMZELX patients due to candidiasis was 0.4%. Oral candidiasis cases were typically treatable with antifungal therapy, and the median treatment duration of antifungal therapies was 12 days. Of the patients who experienced oral candidiasis in the first year, the majority experienced only one event.
I should also mention that cases of elevated serum transaminases were reported in clinical trials. During the 16-week period of the placebo-controlled trials, 1% of patients treated with BIMZELX experienced liver serum transaminase elevations more than three times the upper limit of normal, while 0.6% of subjects treated with placebo saw the same elevations. In some subjects, these elevations resolved with continued treatment. In others, they resolved after treatment was discontinued.
Because of this, monitor the liver function of patients treated with BIMZELX by testing liver enzymes, alkaline phosphatase, and bilirubin at baseline, periodically during treatment with BIMZELX, and according to routine patient management. If elevations do occur and seem to be related to BIMZELX, treatment should be interrupted while the cause is investigated. If it is determined to be due to BIMZELX, then treatment should be stopped.
I also want to mention, during the 16-week period of the placebo-controlled clinical trials, higher rates of passive suicidal ideation were reported in BIMZELX-treated subjects than in placebo-treated subjects.
Additionally, during the open-label extension trial, one completed suicide was reported in a BIMZELX treated subject. As stated in the label for BIMZELX, a causal association between treatment with BIMZELX and increased risk of suicidal ideation and behavior has not been established. The overall rate of suicidal ideations and behaviors with 0.13 incidents per 100 patient-years. It can be noted that the literature has shown that the background rates of suicidal ideations and behaviors in a psoriasis patient population are 0.09 to 0.54 incidents per 100 patient-years.
Physicians and patients should weigh the potential risks and benefits of treatment before using BIMZELX in patients with a history of severe depression or suicidal thoughts or behavior. Additionally, patients should be monitored for new or worsening depression, suicidal ideations or mood changes. If these symptoms do occur, they should seek medical attention immediately.
Important safety information includes warnings and precautions for the risk of suicidal ideation and behavior, infections, tuberculosis, liver biochemical abnormalities, inflammatory bowel disease, and the use of live immunizations in patients treated with BIMZELX. The most common adverse reactions, those that occur in at least 1% of patients on BIMZELX, are upper respiratory infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, Herpes Simplex Infections, acne, folliculitis, other Candida infections, and fatigue.
Dr. Blauvelt:
Dr. Armstrong, based on your clinical experience, how would you characterize the safety profile of BIMZELX?
Dr. Armstrong:
I would characterize BIMZELX as consistent. A safety profile that's consistent across eight Phase 2 and 3 clinical trials up to about three years. Let's think about that—that's three years of safety at approval.
Dr. Blauvelt:
And Dr. Armstrong, what other information factors into your decision about whether a particular biologic is right for your patients?
Dr. Armstrong:
I look for a dosing schedule that my patients can stick with over time.
Dr. Blauvelt:
I'm glad you brought up the topic of dosing. Dr. Strober, could you tell us about the dosing schedule for BIMZELX and how it is administered?
Dr. Strober:
Absolutely. I'll answer your second question first, “How is BIMZELX administered?” Patients have two options: they can choose between a prefilled syringe or an autoinjector.
Now for your first question, BIMZELX offers the fewest number of doses within the IL-17 class. The recommended dose of BIMZELX is 320 milligrams given as two subcutaneous injections of 160 milligrams each. This dose is given at Weeks 0, 4, 8, 12, and 16 and every eight weeks thereafter. For patients weighing 120 kilograms or more, a dose of 320 milligrams every four weeks after Week 16 may be considered.
Dr. Blauvelt:
Dr. Strober, how would you characterize the dosing schedule for BIMZELX?
Dr. Strober:
I'd say BIMZELX offers convenient dosing, and here's why I say that. After the initial 16-week treatment period, BIMZELX offers just four maintenance doses in the first year for patients on a dosing schedule of one dose every eight weeks.
Dr. Blauvelt:
Dr. Armstrong, you mentioned a moment ago that you look for a dosing schedule that works for your patients—in short, a schedule they can stick with over time. Dr. Strober, tell us about your experience and your practice.
Dr. Strober:
My patients find BIMZELX dosing schedule very convenient every four weeks through 16 weeks, and then every eight weeks thereafter, making it a very unique dosing schedule for an IL-17A pathway inhibitor. That said, it can be tailored for patients who weigh 120 kilograms or more. Being an every four-week dose after Week 16, that might allow heavier patients as good a response as a lighter patient would experience on a Q8W dose.
Dr. Blauvelt:
Dr. Armstrong, how does a biologic’s dosing schedule impact your decision on whether to prescribe a biologic and why?
Dr. Armstrong:
I think that naturally, our patients want something that's dosed infrequently. So, if everything else being equal, I tend to go for a biologic with lower dosing frequency.
Dr. Blauvelt:
We've almost reached the end of our program today, so let's share our final topic—patient support.
As providers, several considerations factor into our decisions to prescribe a drug to our patients, and access is a big one. Dr. Strober, can you talk about what UCB has done to help provide access to BIMZELX for patients?
Dr. Strober:
Sure thing. Eligible, commercially insured, patients who experience denial or delay in coverage can connect with the BIMZELX Bridge Program. This program enables patients to get rapid access to their first dose of BIMZELX before submitting a prior authorization. Eligible patients with commercial insurance pay as little as $5 per dose of BIMZELX or $15 per dose while eligibility is being determined. Making sure my patients can access the drug is extremely as important.
And the BIMZELX Navigate program is supporting patients and providers with robust online resources. Nurse Navigators help patients with questions about insurance, payment assistance, and more. It's this kind of support and access that allows us to get the treatment we want to prescribe into the hands of our patients. I'm excited to help my patients achieve the results they want.
Dr. Blauvelt:
Now before we finish and open the floor for audience questions, I want to ask you both for some closing thoughts. What are the top three reasons you're excited about BIMZELX and why should your peers consider BIMZELX as a treatment option for their appropriate patients?
Dr. Armstrong:
I'm really excited that BIMZELX is one, the first and only approved biologic, that selectively targets both IL-17A and IL-17F. And two, it has a convenient dosing schedule of every eight weeks after initiation, and three, that BIMZELX has a consistent safety profile for patients with plaque psoriasis.
Dr. Strober:
And I think the three most compelling reasons to consider BIMZELX are: one, rapid; two, complete; and three, maintained. And much like my quick answer there, BIMZELX consistently delivers rapid, complete, and sustained clearance—from the very first dose—that can be maintained up to three years in some patients.
Dr. Blauvelt:
Thank you both for sharing your perspectives about BIMZELX.
And now we'll be happy to take questions from our audience.
So our first question is, why would I need another option to treat psoriasis? There are already so many biologics available.
Dr. Strober, do you want to take this one?
Dr. Strober:
Sure. Through my experience with my own patients, BIMZELX delivers rapid relief for patients after the first dose Week 0, and then following up with these patients approximately four weeks later, you see most of the burden of the psoriasis has been removed.
As I mentioned earlier, BIMZELX delivers consistent results from the very first dose, as shown by the greater than 80% mean PASI improvement at Week 4 across each of the four Phase 3/3B trials. Primary endpoints across each of the head-to-head Phase 3/3B trials tested for superiority at Week 16. BIMZELX exhibited superiority, achieving PASI 100 in more patients than secukinumab in BE RADIANT and PASI 90 did in more patients than placebo and ustekinumab in BE VIVID and adalimumab in BE SURE at Week 16. At Week 48 in the BE RADIANT trial, 84% of patients achieved PASI 90, and 67% achieve PASI 100. Further results from the BE BRIGHT OLE show that not only does BIMZELX offer rapid clearance, but also complete clearance, PASI 100, up to about three years for the majority of patients.
Dr. Blauvelt:
Okay, the next question is, what was the treatment history of the biologic-experienced patient population in the four Phase 3/3B clinical trials?
Dr. Armstrong, would you like to answer this one?
Dr. Armstrong:
This is a great question because the data really gives us some real-world results.
BIMZELX has been evaluated in 2,223 patients with psoriasis across four Phase 3 and 3B clinical trials, and among these 36% were biologic experienced. And when we look at that 36% total-biologic experienced patients, 53% had prior IL-17 inhibitor exposure, 42% had a prior anti-TNF exposure, 16% had a prior IL-12/23 inhibitor exposure, and 14% had a prior IL-23 inhibitor exposure. And it's important to note that some patients had prior exposure to more than one biologic.
The next question from our audience is, I thought all IL-17 inhibitors work the same. Can you explain in more detail the importance of targeting IL-17F in addition to IL-17A?
Dr. Blauvelt, would you like to address this one?
Dr. Blauvelt:
Of course. IL-17A and IL-17F production can come from both IL-23 dependent and IL-23 independent sources. Both IL-17A and IL-17F are overexpressed pro-inflammatory cytokines implicated in psoriasis pathogenesis.
Targeting IL-17A alone only partially interferes with IL–17–mediated inflammation. IL-17A inhibitors interfere with the IL-17A/A and IL-17A/F dimers, preventing them from binding to and activating the IL-17RA/C receptor, which is on the surface of the keratinocyte. However, IL-17A inhibitors do not intercept the IL-17F/F dimer. It remains free to bind to and activate the IL17RA/C receptor, leading to the release of other inflammatory chemokines and continuing to drive psoriasis pathogenesis.
This is how the BIMZELX mechanism of action differs from other IL-17 inhibitors. BIMZELX provides more inhibition of inflammation from the blocking of IL-17A and IL-17F compared with IL-17A alone. This means it binds to all three IL-17 dimers implicated in psoriasis pathogenesis: IL-17A/A, IL-17A/F, and IL-17F/F.
BIMZELX is the first and only approved biologic to selectively target the overly expressed IL-17A and IL-17F cytokines in plaque psoriasis, providing more inhibition of inflammation and the blocking of IL-17A and IL-17F compared with IL-17A alone.
The next question from our audience is, can you provide more information on complete clearance with BIMZELX? This isn't a realistic treatment goal for the majority of my patients.
Dr. Strober, can you share here?
Dr. Strober:
You bet. In fact, when you use BIMZELX, it is a realistic treatment goal to achieve PASI 100. When I have administered BIMZELX to my patients, it is true that about two-thirds can achieve PASI 100 at Week 16 and even keep that response out to Week 48 and beyond.
At Week 16, BIMZELX delivered complete clearance and exhibited superiority for PASI 100 after four doses over secukinumab (after seven doses) in BE RADIANT and adalimumab (after nine doses) in BE SURE. Pooled results from BE READY, BE VIVID, and BE SURE showed a PASI 100 of 63% at week 16 with BIMZELX treatment.
In the BE BRIGHT OLE complete skin clearance, PASI 100 was maintained up to approximately three years in the BIMZELX Q8W/Q8W, or maintenance/OLE, dosing group.
Dr. Blauvelt:
Another question from our audience is, my patients are happy, but over time their treatment loses efficacy. While my patients want rapid response, they also want treatment that lasts long term. Can you share your clinical experiences?
Dr. Strober, would you like to address this as well?
Dr. Strober:
Yes. Through my own experience with my own patients receiving BIMZELX, patients do get a rapid response and yet they maintain it over a longer period of time, such that at Week 48 and onward, patients who achieve say PASI 100 or PASI 90 are keeping that response.
As I mentioned earlier, BIMZELX delivers consistent results from the very first dose as shown by at least 80% mean PASI improvement at Week4 across each of the four Phase 3/3B trials. In the BE RADIANT trial, 84% of patients achieved PASI 90 and 67% achieve complete clearance, PASI 100, at Week 48. Further results from the BE BRIGHT OLE show that BIMZELX not only offers rapid clearance, but it provides complete clearance, PASI 100, up to three years for patients as well.
Dr. Blauvelt:
All right, the next question from our audience is, can you explain what it means to have three years of efficacy and safety from the start? So, I can address this one.
So, BIMZELX has three years of efficacy and safety at approval, and the results have been repeated across trials. To me, that is both impressive and reassuring.
So, in the BE RADIANT and BE SURE clinical trials, approximately 70% of patients achieved complete clearance, PASI 100, with BIMZELX after about one year. And in the BE BRIGHT OLE trial, 82% of Week 16 PASI 100 responders maintained complete clearance up to about three years.
So to me, this is very unusual whenever we have a biologic approved for psoriasis. In the past, we've had usually one year of data, sometimes two, and that's all we've had to base our decisions on. So, when we see from the get-go three-year data when we see this drug being used already in European countries and across the world, it should give us much more assurance about the data set that's out there regarding BIMZELX.
Dr. Armstrong:
The next question from our audience is, in the long term, what is the incidence and recurrence of candidiasis? I think I can take this one.
Data from a pooled short-term analysis (Weeks 0-16) showed that 9.1% of patients developed Candida infectious with BIMZELX versus 0% for those taking the placebo. The exposure-adjusted incidence rates in the long-term analysis, and that's up to about three years, across all doses of BIMZELX was 11.5 incidences per 100 patient-years.
Let me elaborate more about an analysis focus on recurrence. 15.4% of BIMZELX patients experienced oral candidiasis in the first year. Of the patients who experienced recurrence of oral candidiasis within the first year, about two out of three patients experienced only one recurrent event. Incidence rates decreased with prolonged BIMZELX exposure over two years. And finally, the safety data observed over three years of BIMZELX treatment were consistent with those observed over two years.
Dr. Blauvelt:
The next question is also about candidiasis. How was oral candidiasis treated or managed in the clinical trial program? So, I can address this one too.
Oral candidiasis cases were mild to moderate and led to few discontinuations. Cases were typically treated with antifungal therapy at the discretion of the investigator—mostly Nystatin and/or Fluconazole.
So, in my experience, we did see oral candidiasis in this trial that the rates were slightly higher than what we have seen with the previous IL-17 inhibitors, but it, [DD1] in my experience, had no major impact either on the patient experience or on the patient's remaining on drug. So we would ask about it at every visit. We would treat it if we saw it. And it was easily treated and patients tended to stay on the drug, stay on the study. Most of the cases were single cases they didn't recur.
Occasionally, we have seen in the trial program a recurrent case and we would simply treat that again the second time without any issues. So, I think as dermatologists, I think most of us are comfortable with oral candidiasis both diagnosing and treating it, and I think that's how clinicians should view the BIMZELX candidiasis data. Just be aware of it, ask patients about it, provide the simple treatment, but don't let it really, I think, influence you, in terms of prescribing or not prescribing. So to me, it's pretty much a non-issue and was easily handled.
Another question reads, how often do I need to monitor for elevated liver transaminase?
Dr. Armstrong, would you like to address this one?
Dr. Armstrong:
Absolutely. The label states to monitor liver function enzyme at baseline and periodically during BIMZELX treatment, as well as according to routine patient management. In my practice, I will also look at patient-specific risk factors when I think about timing and frequency of monitoring. It's also important to note that monitoring requirements are not tied to the onset of the elevated liver serum transaminase.
The next question from our audience is, how many patients discontinue BIMZELX due to hepatic adverse events? I'll address this one as well.
Among 2,186 patients treated with BIMZELX over one year in Phase 3/3B study, 11 subjects, or 0.5%, withdrew due to hepatic adverse events. These included five subjects who withdrew due to hepatobiliary disorder events and six subjects who withdrew due to elevated LFTs. In the second year of the Phase 3 and Phase 3B open-label extension pool were two additional discontinuations due to hepatic adverse events in both cases LFT elevations.
Dr. Blauvelt:
Another question reads, can you provide more information on the hepatic adverse events that occurred with BIMZELX?
Dr. Armstrong, would you address this one?
Dr. Armstrong:
Yes. In the BIMZELX psoriasis clinical studies, the majority of hepatic treatment-emergent adverse events, or TEAEs, and biochemical changes they were transient, asymptomatic, did not result in clinical sequelae, and typically reversed either with continued treatment with BIMZELX or shortly after discontinuation when therapeutic levels of BIMZELX remained.
Dr. Blauvelt:
Another question reads, could you explain the risk of suicidal ideation and behavior with BIMZELX?
Dr. Armstrong, would you address this one?
Dr. Armstrong:
Yes. During the 16-week placebo-control period of BE READY and BE VIVID, higher rates of passive suicidal ideation were reported in BIMZELX-treated subjects than in placebo-treated subjects. In the open-label extension study, one completed suicide was reported in a BIMZELX-treated subject. The subject had no reported psychiatric history but had reported financial concerns. The overall rate of suicidal ideations and behavior across the psoriasis clinical trial program was 0.13 per 100 patient-years. The reported background rates in a psoriasis patient population are 0.09 to 0.54 per 100 patient-years.
It should be noted that a causal association between treatment with BIMZELX and increased risk of suicidal ideation and behavior has not been established. However, we as clinicians should weigh the potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior prior to prescribing BIMZELX.
Dr. Blauvelt:
Our next question reads, my patients tell me dosing schedules are challenging for them. What is your clinical experience, Dr. Strober?
Dr. Strober:
Well, it depends on the medication. Some dosing schedules are challenging. With BIMZELX though, it's Q4W dosing through Week 16, that's convenient, and then it converts to Q8W thereafter. Except for some patients who weigh 120 kilograms or more, you can choose to keep them at the Q4W. That to me is not only tailored dosing, but convenience no matter how you slice it.
As mentioned in the presentation, BIMZELX has the fewest number of doses within the IL-17 class. The regimen includes one dose every four weeks for 16 weeks, then one dose every eight weeks thereafter, with one dose equaling two injections.
Dr. Blauvelt:
Another question from the audience. My patients tell me that gaining access to treatment is very stressful. What is your clinical experience, Dr. Strober?
Dr. Strober:
Well, access can be stressful, but it's not with BIMZELX. That's why I'm excited for the commercially insured eligible patients who experience a delay or denial in coverage, the first dose of BIMZELX can be made available before submitting a prior authorization. More information about this can be found online at BIMZELXHCP.com.
Dr. Blauvelt:
As we close out our discussion on BIMZELX, I want to thank our guests, Dr. April Armstrong and Dr. Bruce Strober, for their insights.
Dr. Armstrong:
It was a pleasure. Thank you.
Dr. Strober:
It was my pleasure. Thank you very much.
Dr. Blauvelt:
I'm Dr. Andy Blauvelt, and my thanks to you, our audience, for joining us for this live broadcast. Please stay tuned for Important Safety Information.
Announcer:
Important Safety Information.
Suicidal Ideation and Behavior
BIMZELX® (bimekizumab-bkzx) may increase the risk of suicidal ideation and behavior (SI/B). A causal association between treatment with BIMZELX and increased risk of SI/B has not been established. Prescribers should weigh the potential risks and benefits before using BIMZELX in patients with a history of severe depression or SI/B. Advise monitoring for the emergence or worsening of depression, suicidal ideation, or other mood changes. If such changes occur, advise to promptly seek medical attention, refer to a mental health professional as appropriate, and re-evaluate the risks and benefits of continuing treatment.
Infections
BIMZELX may increase the risk of infections. Do not initiate treatment with BIMZELX in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing BIMZELX. Instruct patients to seek medical advice if signs or symptoms suggestive of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer BIMZELX until the infection resolves.
Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with BIMZELX. Avoid the use of BIMZELX in patients with active TB infection. Initiate treatment of latent TB prior to administering BIMZELX. Consider anti-TB therapy prior to initiation of BIMZELX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients for signs and symptoms of active TB during and after treatment.
Liver Biochemical Abnormalities
Elevated serum transaminases were reported in clinical trials with BIMZELX. Test liver enzymes, alkaline phosphatase and bilirubin at baseline, periodically during treatment with BIMZELX and according to routine patient management. If treatment-related increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt BIMZELX until a diagnosis of liver injury is excluded. Permanently discontinue use of BIMZELX in patients with causally associated combined elevations of transaminases and bilirubin. Avoid use of BIMZELX in patients with acute liver disease or cirrhosis.
Inflammatory Bowel Disease
Cases of inflammatory bowel disease (IBD) have been reported in patients treated with IL-17 inhibitors, including BIMZELX. Avoid use of BIMZELX in patients with active IBD. During BIMZELX treatment, monitor patients for signs and symptoms of IBD and discontinue treatment if new onset or worsening of signs and symptoms occurs.
Immunizations
Prior to initiating therapy with BIMZELX, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid the use of live vaccines in patients treated with BIMZELX.
MOST COMMON ADVERSE REACTIONS
Most common adverse reactions (≥ 1%) are upper respiratory infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, Herpes Simplex Infections, acne, folliculitis, other Candida infections, and fatigue.
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