25th EADV Congress. Late-breaking insight: Tildrakizumab Phase 3 data in psoriasis

25th EADV Congress. Late-breaking insight: Tildrakizumab Phase 3 data in psoriasis


Dear colleagues, my name is Professor Kristian Reich here. I’m a dermatologist from Hamburg, but I’m
not in Hamburg right now. I’m in Vienna, Austria, where we have the
25th Meeting of the European Academy of Dermatology and Venereology. When it comes to the management of psoriasis,
there have been, in my eyes, two big highlights. One is the introduction of the Phase 3 data
of the IL-23p19 inhibitors, and then of course, more data on the IL-17A inhibitors; so new
data on our two new classes of targeted therapies. I would like to present two late breakers
to you. And you know that the late breakers—this
is the really hot stuff that gets selected lately, and the room is crowded with people. The first late breaker is on tildrakizumab,
which is an IL-23p19 inhibitor. And let’s not forget: we have IL-12 and IL-23;
they are both heterodimers, they are composed of two molecules. They share one molecule, this is called p40—this
is what ustekinumab blocks. And then we have the IL-23–specific part,
which is p19. So if you block p19, you selectively block
IL-23, but you will not block IL-12. The hope, of course, is that knowing that
IL-23 is the sweet spot in psoriasis, by doing so, you will increase the levels of response
but maintain the nice safety and convenience profile that we know Stelara has. So tildrakizumab: two Phase 3 studies, one
comparing two doses of tildrakizumab (100 and 200 mg per syringe) to placebo. The other study additionally having an active
comparator arm with etanercept—where etanercept was given 2 × 50 mg the first 12 weeks (so,
the highest dose that is in the label) and, from then on, continued with 50 mg per week. How is tildrakizumab injected? Like Stelara. So you give 1 shot at baseline, one shot after
4 weeks, and then every 12 weeks thereafter. If you look at the efficacy data, and I’m
going to focus on PASI 75, PASI 90, and PASI 100— although PASI 75 and PGA 0/1 was the
co-primary endpoint. If you focus on the PASI data, we first look
at Week 12. We see that approximately 60% of the patients
with both tildrakizumab doses achieve a PASI 75 response, so that is not so high. But if you go to Week 28—of course, placebo
stops at Week 12—but if you continue to give tildrakizumab and the Week 28 data was
reported, you get to 80% PASI 75. PASI 90—the new treatment goal, very likely,
and the new level of response we want to see, knowing that more patients achieving a PASI
90 will say, “I’m no longer impacted by my psoriasis in my daily life”—again,
discrepancy between the Week 12 primary endpoint and the Week 28 findings. PASI 90 Week 12 around 40%; again, that’s
similar to what we had with drugs like Humira and Stelara. But then at Week 28, 60% PASI 90. And if we look at PASI 100 at Week 28, 30%
PASI 100. So what is my interpretation of this? We have here a p19-selective inhibitor, where
you probably need to wait a little bit longer until it goes full throttle. The primary endpoint data, that’s not the
full power we can expect from this drug; you have to wait a little bit longer. It seems to take a little bit longer until
this drug goes full throttle, and Week 28 data with PASI 90: 60%, PASI 100: 30%, this
does look pretty good. Safety in these relatively small studies,
relatively short period of time—I feel this only gives you a first glimpse into the safety
profile, and I can summarize and say there was no safety signal here, no unexpected event. Comparing tildrakizumab with etanercept, no
real differences in the safety profile. So a promising candidate within the group
of the IL-23p19 inhibitors, and more data—more long-term data, of course—to come from the
Phase 3 program.

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