25th EADV Congress day 4 highlight: Emerging therapies for psoriasis

25th EADV Congress day 4 highlight: Emerging therapies for psoriasis


So for me today, the key highlights of our
discussion related to an attempt to look at the differentiation of the emerging and the
recently emerged therapies. So specifically what we did today was try
to have a 30,000 ft view, or global view, of the field of emerging and recently emerged
therapies by examining the interleukin-17s, looking at the p40 IL-12/-23 ustekinumab (STELARA), and also you know as a bridge to looking
at the new interleukin-23s. So it was quite interesting when you try to
do this in two ways; we did it in an evidence base and then kind of an eminence base. So the evidence base to it was that we looked
at the pivotal results for the interleukin-17s, and what comes across is that the PASI 75/IGA
co-primary endpoints—all these studies looked at Week 12—and it was important as we looked
at these to raise a few caveats. We basically said, “You know you gotta make
sure that they’ve done a similar study design, same statistical endpoints, have we controlled for the fact that the patient populations were the same?” So these are a number of the considerations
you have to have, and recognizing that when you do these even evidence-based analyses
that they’re not done in a head-to-head fashion. Having said that, it’s natural to look at the data that’s out there and try to kind of see where it all fits. And with those caveats in hand, we truthfully
thought that amongst the IL-17s the efficacy range for secukinumab at primary endpoint
is around 77%–82%, to ixekizumab around the 80% up to 89%–90%, and for brodalumab
still in the 80% range. So really what we’re seeing is drugs that
are in approximately this 80% PASI 75, which is a step up from what we’ve had with TNF antagonists. Now of course the caveat here is that the
peak efficacy looks like it’s a little later than Week 12—it looks like it’s probably
Week 16 or maybe a little later. And if you look at data that has those endpoints
we’re seeing upwards, for secukinumab we saw into the 80%–90% range and also for ixekizumab
and brodalumab. So it’s really hard to differentiate these
drugs when you look at efficacy. As we look at dosing, again we’re looking
at drugs that are given generally every month—once they’re in maintenance the induction regimens
are a little different between them, but they’re monthly—and the question came up (and here’s
where the eminence comes up), is there can be a difference in countries between what’s
labeled dosing and what is actually done. And so ustekinumab (or STELARA) is a classic
example of that: the labeled dose after induction is to give it by weight—less than 100 kg, greater than a 100 kg—either 45 or 90 every 12 weeks. In reality, in many parts of the world—in
Europe in particular, certainly in Canada, in some parts of the US—there’s a tendency to give it every 8 weeks even though that may not be by label. So the question will become then for the interleukin-17s,
will we be able to use (instead of every monthly dose) every 2-week dosing for ixekizumab and
for secukinumab? And certainly there’s clinical studies ongoing
that are looking at that. So I think the absolute level of efficacy
we’re seeing this range: difficult to discriminate, rapid onset, high effect. And then durability is probably one of the
most important things we discussed as being relevant to the use of these drugs. By durability we’re looking at the ability
to maintain efficacy, and it’s always very important to look at how we’re reporting that
data statistically; non-responder imputation is the preferred method up to a year, beyond
that it becomes a question of what the best endpoint is, but to standardize results across. And what we’re seeing, and we saw this at
first with ustekinumab (with STELARA), was that the durability of these newer molecules
seems to be excellent: we’re retaining a majority of patients at these high levels. Now the other element of efficacy (that although
these weren’t primary endpoints) was the PASI 90 and PASI 100 with these new molecules: we’re seeing ranges around 25% to about 40% achieving a PASI 100, which is clear. PASI 90 around 70% so again a step up from
what we’ve had, a step up has been shown even from one of the most effective drugs we have—STELARA (ustekinumab) —done in a head-to-head fashion with the CLEAR study for example. We’re getting higher levels on these more
stringent endpoints. In terms of whether these higher levels of
efficacy matter, I think there was pretty well consensus among the group that we spoke
today that it does matter and it matters because it matters to patients. As you achieve higher levels of efficacy you
will see that these patients are happier and you can measure that with DLQI, that you get
a 0 or 1 in a higher proportion of these patients who go from PASI 75 to PASI 90 to PASI 100. So it matters because it matters to patients. All right. The other elements that we talked about that
were different as we compared these molecules, related to perhaps other items such as psoriatic
arthritis, such as specific areas like the scalp, the nails; we looked at other areas like pediatrics, flexibility of dosing, and accessibility in the US. Mark Lebwohl mentioned that access can be
not defined necessarily by efficacy, but by what payers are going to agree to give, and that is not at all a clear relationship
as to how that happens. It may not be defined whether it’s cost that
drives it, whether there’s agreements that happened between payers, and that can change,
and it can result in switches. So really, I think it’s a fairly complicated
algorithm, if you will, that results in the ultimate choice of these molecules that can
go well beyond the standard efficacy metrics, and I think the discussion that we had to
me was fascinating in that regard. Now I didn’t talk about the new p19, the interleukin-23
molecules, and the reason for that is that data is embargoed until a few hours. So I’ll leave you with that, and maybe perhaps
come back and talk about the interleukin-23s and how they are going to compare to the interleukin-17s, and to the TNF antagonists, which really essentially, is the state of the field in terms of the
choice and the choices that we have for patients.

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