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Prof Reich on the Results of BE-VIVID and BE-READY, Two Phase 3 Clinical Trials on Bimekizumab, an IL-17A/IL-17F Inhibitor

Kristian Reich, MD, PhD, discusses the results of two phase 3 clinical trials, BE-READY1 and BE-VIVID,2 that tested the efficacy and safety of bimekizumab, a novel IL-17A/IL-17F inhibitor. Dr Reich is affiliated with the Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center in Germany.

Disclosure: Prof Reich was an investigator for both BE READY and BE VIVID.

1. Reich K, Papp KA, Blauvelt A, et al. Efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis: results from BE VIVID, a 52-week phase 3, randomized, double-blinded, ustekinumab- and placebo-controlled study. Presented at: American Academy of Dermatology Virtual Meeting Experience 2020; June 12-14, 2020.
2. Gordon K, Foley P, Krueger J, et al. Efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis: results from BE READY, a 56-week phase 3, randomized, double-blinded, placebo-controlled study with randomized withdrawal. Presented at: American Academy of Dermatology Virtual Meeting Experience 2020; June 12-14, 2020.

Professor Reich:
 The big thing that happened last weekend was the virtual AAD where two of four phase 3 studies that are planned and conducted with bimekizumab in moderate‑to‑serious psoriasis were presented. 
One study is called the BE VIVID. That is a head‑to‑head comparison of the bimekizumab, the new IL‑17 inhibitor, to ustekinumab, a drug that blocks IL‑12 and ‑23 and to placebo. The placebo patients were crossed over to bimekizumab at week 16. The other study, BE READY, was a study where the drug, bimekizumab, was compared to placebo. Then the drug was, at week 16, in responding patients, either continued or taken away. You can see what happens. How quickly does the disease come back?

When I say continued, there are two ways in that it was continued. One with the usual every four week injection, but the other arm every eight week injections. Again, this is very relevant for the daily practice. Patients will want to know, "How often, doctor, do I need to inject this?" Once monthly is already good but once every 8 weeks, I think, most patients would consider as being even more convenient.

Now, what did these studies show? They showed a lot of things, but let me try to carve out what I find and I feel is most important for the practicing the dermatologist to know.

First of all, we saw amazing levels of response when we look at PASI 90 and PASI 100 of almost clear skin, which is often similar to PASI 90. Clear skin being often similar to PASI 100. Very high level of response. To put this in perspective, if I would have psoriasis, really bad psoriasis and a treatment would improve my disease by 90 percent or bring it to clear or almost clear, I could probably go swimming and no one would see that I have psoriasis. Very, very little psoriasis left. A level of response for most patients would say, "I'm no longer bothered by my disease," just to put this in perspective.

We saw very high levels of this PASI 90 and PASI 100 response. PASI 90, 80%, 90%t. PASI 100, 50%, 60% plus. An amazing high level of response. Some of the highest numbers we have seen.

A second piece of information, we saw a very fast onset of response. After 4 weeks after one injection--because bimekizumab was given in the studies 320 mg in one shot every 4 weeks--if you measure the response at week 4, that means after one shot, 75% in one study already had a PASI 75 response and 40% of PASI 90. Four out of 10, after one shot had this very high level of response we talked about. I would think it's fair to say this is the fastest onset of response in psoriasis we have seen with any other drug.

The third piece of information: psoriasis is a chronic disease. Most of my patients have the disease for 10, 15, 20 years. To have a very fast onset of response is nice, is important. What my patients want to know is, "How stable is this, doctor? Can I be sure that if I take this drug my disease will continuously be controlled?" The maintenance of response is important. We can look at 1‑year data here, and we can say that the maintenance of the response was very stable. Almost every patient maintained the response over time.

To put a cherry on the whipped cream, this was also true in this BE READY study where this longer injection interval was tested for the longer injection interval. If you have a PASI 90 response at week 16, it's possible to maintain the good response with 50% of the dose, prolonging the injection interval by a factor of two. It's possible to maintain this response with every 8-week dosing.

To put this again in the big context, the current IL‑17 inhibitors have to be given monthly. The beauty of the 23 inhibitors is that because of their MOA, you can go to every 8 or even every 12‑week injection intervals and you have this very stable response.

I'll probably use a little bit of watering your mouth language now, but what this data seems to indicate to me is that this IL‑17 2.0 inhibitor bimekizumab that blocks F in addition to A, combines the good things we have seen with the IL‑17A inhibitors with the good things we have seen with the 23 inhibitors when it comes to onset of response, but also maintenance of response.

If you ask patients, "What do you want?" Patients don't know PASIs. They don't know Investigator Global Assessments. They want to say, "Look, I want to live a normal life." When you dig a little bit deeper, you also hear from patients, "I want to have trust in my therapy." This speaks to the fact that the novel psoriasis is a disease with a genetic susceptibility. No therapy is curing the disease. You always live with this fear, "Does the disease come back?" This is what it comes down to, how big can the trust of the patient be? "OK, now I have a good response. How big can my trust be that the good response I've achieved after 16 weeks or whatever, that this is maintained over time?"

If you put yourself in the patient perspective, this point becomes extremely understandable. Confidence. "My disease with this therapy is controlled, and will remain controlled over months and years." Obviously, the years I cannot talk about with bimekizumab because we only have 1‑year data to look at right now. The 1‑year data we have to look at indicates a very stable response level. There are different statistical ways of looking at long term data. Don't forget that in clinical trials, patients drop out. They do not always drop out for bad reason. Sometimes they are clear. They fall in love. They marry. They move away to Italy, and they no longer come to your clinical trial site in Chicago. There are also good reasons that make patients dropping out. The analysis that was used here is so conservative that it imputes every missing data as a non‑responder. Even if you left the study clear, my example with the honeymoon, you were imputed as a nonresponder.

Based on this conservative analysis, if you look at the 1‑year data, you see a very stable response. Almost all patients maintain their response over this 1‑year period.

As I alluded to earlier, for a drug that inhibits IL‑17, that is very important to see many doctors would think that 23 inhibitors are a little better in maintaining the response than 17 inhibitors. At least, that's the perception. I'm not sure it's always backed by data, but that's the perception. To see here an absolute 23 inhibitor‑like maintenance of the response, at least for this one‑year period, this is what brings me to saying, "Hey, there may be more to this blocking F in addition to A than just creating a better 17 inhibitor. That may give you a drug profile that is completely different from just an IL‑A inhibitor. It may start to integrate elements that until now we have only seen for 23 inhibitors. Complicated answer.

Simple answer, great maintenance. Absolute nice maintenance of the control over this one‑year period data that would reassure my patients that they can have this trust in this therapy.

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