Mark Lebwohl, MD: Let’s move on to UltIMMa.
George Han, MD, PhD: I’ll take that. It was a very interesting trial design in that they also abandoned PASI [Psoriasis Area and Severity Index] 75 completely. They didn’t even talk about it. In this clinical trial design, a patient getting to PASI 89 [89%] improvement is completely a failure at 16 weeks.
Brad Glick, DO, MPH: Isn’t that incredible.
George Han, MD, PhD: It’s incredible, right. So about three-quarters of the patients or so got to PASI 90; close to that got to sPGA 0/1. So really great data. But what I think is really important coming out of those data points is that out to 1 year the PASI 100 continues creeping up to the point that at 52 weeks, the PASI 100 clearance is over 50%, which is really unique among all of our agents. And that I think is a very objective endpoint, you will be clear of psoriasis.
So that agent has that advantage. But also what’s interesting if you break down the trial data looking at UltIMMa, the comparator with ustekinumab, there’s an interesting plot that they show looking at different patient demographic characteristics at trial entry, looking at weight classes, looking at previous exposure to biologics, biologic failures. And if you look at ustekinumab, it seems a little fickle because it jumps around depending on what the patient characteristics are. But if you look at risankizumab, this medication doesn’t care what you’ve been on, doesn’t care if you’ve failed.
Brad Glick, DO, MPH: It doesn’t budge.
George Han, MD, PhD: It doesn’t care what weight you are.
Scott Gottlieb, MD: It also doesn’t seem to lose efficacy toward that 12-week mark.
George Han, MD, PhD: Yes.
Scott Gottlieb, MD: When they put the 2 graphs of ustekinumab and risankizumab next to each other, you saw a little sawtooth effect of ustekinumab. As patients were getting closer to the 12-week mark, they were losing some of the efficacy. Within the 12 weeks dosing schedule, they did better in-between the 12 weeks than they did at week 12 as opposed to risankizumab, where patients were rock steady the whole time.
Brad Glick, DO, MPH: And we clearly see that in clinical practice with ustekinumab. That is a drug in my camp, I have many patients still on the drug, and I have many who are dosed at every 8 weeks.
George Han, MD, PhD: I remember we would actually try to figure out when the insurance company would pay for another syringe. I found that most of them pay at around 72 to 75 days. So you can actually, without even trying to fight for it, get it a little more frequently. And that actually shows up in the long-term data for ustekinumab, which look really good, but the investigators are actually allowed to change the dosing regimen and frequency if they wanted to.
Brad Glick, DO, MPH: I believe in Phoenix 2 there was an arm that actually had patients who were not responders. They were between PASI 50 and PASI 74. Some of those patients were randomized to an every-8-week arm too. So there is some justification, and they did better.
Mark Lebwohl, MD: Yes.
Scott Gottlieb, MD: I think the 90 mg group did better, but I think that is some justification there.
Mark Lebwohl, MD: Have any of you tried that with current insurers? At least in my area, we’ve tried to take, for example, guselkumab in the few patients when it’s not working well and give it every 7 or every 6 weeks; they will not me do it. The only option you have is to throw in samples. It’s interesting that we’re so almost blasé about giving more drug because these drugs are so safe. I’ll just say, look at the package insert for secukinumab, Cosentyx. It’s 2 injections a week for 5 weeks. It’s a once-a-week.
Brad Glick, DO, MPH: It’s an induction.
Mark Lebwohl, MD: We had this twice—we’ve written up 1 of them—where the patient took it Monday, Tuesday, Wednesday, Thursday, and Friday.
Scott Gottlieb, MD: And Saturday they were clear.
Mark Lebwohl, MD: And the dermatologist called me and was really nervous. And I said, “Don’t worry, be happy, your patient is going to really get a good quick response.” In the package insert for secukinumab, they dosed as high as 10 times the approved human dose. And it’s the package insert. There are also over 100 cases of overdose with that drug, and there are no adverse events of note.
Scott Gottlieb, MD: And I want to add that there are probably thousands of cases of overdose with ustekinumab-treated patients. For Crohn disease, it’s given at much higher doses than psoriasis patients. And so, I think we all are more comforted by that dosing schedule for Crohn disease in treating our psoriasis patients.
Mark Lebwohl, MD: It actually brings us to the safety of blocking IL-23 and [interleukin-23] IL-17, because it appears that with that pathway, people born IL-17 deficient get yeast infections. They get chronic mucocutaneous candidiasis. They get tinea infections and yeast infections. With IL-23, I’m not aware of people who are born just deficient in IL-23, but IL-12/23, p40 deficient people, get 2 infections. They get salmonella infections, and I don’t believe there’s a single patient on any of these drugs who has gotten a salmonella infection. And the other infection they get is mycobacterial infections. In fact, many of them are discovered when at birth they’re given BCG [Bacille Calmette-Guérin], which is a live mycobacterium. And in those patients, the BCG disseminates. There actually are patients who can be very ill from BCG vaccinations when they’re deficient in p40.
Well, we’re not blocking IL-12, but we are blocking IL-23. And so that’s why probably in the package insert we have this caution about tuberculosis [TB], even though in practice and in the clinical trials, reactivation of latent TB has not been a problem.
Transcript edited for clarity.