PracticalDermatology

FDA last month approved Cibinqo (abrocitinib, Pfizer), an oral, once-daily, Janus kinase 1 (JAK1) inhibitor, for the treatment of adults with refractory, moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

The safety and efficacy of Cibinqo were evaluated in three Phase 3, randomized, placebo-controlled clinical trials. Both the 100mg and 200mg doses were shown to provide statistically significant improvements in Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), and Peak Pruritus Numerical Ratings Scale (PP-NRS), compared to placebo.

Ahead, study investigator Jonathan Silverberg, MD, PhD, MPH from the Department of Dermatology at The George Washington University School of Medicine and Health Sciences discusses the data and significance of the approval.

What is the significance of the approval of abrocitinib for adults with moderate-to-severe atopic dermatitis?

Jonathan Silverberg, MD: Patients with moderate to severe atopic dermatitis are a challenging subset of patients to manage. Burden of disease is significant, and there is a lot of unmet need. We have had limited options to date to be able to achieve good control of the disease. We really need more options—and more potent options.

The approval of Cibinqo gives us a new option in general, but with a lot of nice features that fill a lot of the unmet needs in moderate-to-severe disease. First, it is an oral option. Patients almost always prefer oral over injectable therapy.

Cibinqo provides a treatment approach with outstanding efficacy and has arguably set the bar in the field for efficacy. It also works very rapidly, which is important. Many patients with atopic dermatitis will experience rapid onset flares and need rapid control of the symptoms and reduction of itch.

It’s an important addition to our toolbox, something that we’ve waited for a long time and we’re excited to have now.

What stands out to you in terms of the efficacy data from the Phase 3 trials?

Dr. Silverberg: We saw two doses studied in the Phase 3 clinical trials. The higher 200mg dose is arguably one of the most effective therapies we’ve seen for moderate-to-severe disease. The 100mg dose is a little less effective but still very effective. The FDA label recommendation is to start at the 100mg dose, which is in of itself a very impressive dose. We have dose flexibility with the approval of both doses. If the 100mg dose is not adequate, we can increase to 200mg.

I think that dose flexibility becomes an important consideration. We always want to use the lowest amount of medicine possible, and this gives us options clinically to tailor therapy to patients’ needs.

Speed is important. When patients experience rapid improvements, not only are they improved, but seeing early benefits often enhances adherence and patient satisfaction.

Within the clinical trials, a large proportion of patients who were enrolled in the studies were patients who had previously used other systemic agents and really severe cases. Despite those past exposures and perhaps not doing well on those therapies, they still did quite well on Cibinqo.

Do you have any thoughts on the importance of looking at that itch component and how Cibinqo performed in that regard?

Dr. Silverberg: Itch is not only the most common symptom of AD, it’s the most burdensome symptom of the disease. Itch is the number one driver of healthcare utilization—why patients make treatment decisions and change treatments. If dermatologists really want to understand the burden of this disease and monitor treatment response, they must ask about itch. I would argue other symptoms too, but at the very least, itch.

For any therapy to really hit its mark in the real world, it has to work well for itch. Not only was Cibinqo effective for itch, but it was very rapidly effective. Within a matter of days there’s dramatic improvements with respect to itch.

What stood out to you in terms of the safety and tolerability of Cibinqo in AD?

Dr. Silverberg: The tolerability overall looks quite good. There is a little bit of headache, a little bit of nausea that comes up. But generally speaking, it is quite well tolerated. In terms of safety, overall, the safety profile looks good.

The challenge that comes up across the class of JAK inhibitors, and Cibinqo is included within that, is that there are some serious adverse events that can happen. Fortunately, they are rare events. That’s the key thing to contextualize. These are still being studied and will be studied in the real world, and we’ll learn even more about just how commonly they happen in atopic dermatitis.

The label is reflective of the class—even including things that didn’t happen in the clinical trials for atopic dermatitis, or maybe happened with just one or two events. But because of class-wide concerns, it ends up in the label.

It’s important for dermatologists and other clinicians to really familiarize themselves with the potential class-wide adverse events, serious adverse events, and boxed warnings. And it has to be a fundamental part of the shared decision-making conversation. And the patient should understand that these are concerning risks but that, fortunately, they are rare.

I think dermatologists also need to be comfortable with the laboratory monitoring. Fortunately, high grade laboratory anomalies were quite rare in the clinical trials. But the label recommends that we do blood work, so we will do blood work. Dermatologists should get familiar with the recommended time points for checking blood work and how to monitor that.

What more are you interested to learn in terms of patient data or real-world clinical use of Cibinqo?

Dr. Silverberg: We’ve got a lot of rich data on the safety profile and we know a lot, but we always want more. Given the class-wide safety concerns, I’d love to be able to see more real-world studies looking at pharmacovigilance and long term safety.

There are some nuances in the FDA label regarding the recommended dosing and requirement, or suggestion, to have had an inadequate response to a previous systemic therapy. Those nuances differ slightly different from how it was studied in the clinical trials. It would be nice for us to get more data in the real world for that labeled suggested use. I think would be valuable for us.

In terms of in the clinic, I think there’s a lot of versatility to this drug. I think that there’s the potential to use it in a lot of different ways, but all being on label within that moderate-to-severe atopic dermatitis patient population. Some patients have chronic disease with six months or more, maybe even 12 months, of active disease and need a daily continuous therapy. When given a choice between a biologic or an oral agent, like Cibinqo, they may very well prefer the oral agent. They may be averse to shots and also may not like the idea of being on a therapy continuously with no clear end in sight. Cibinqo becomes a very attractive option for those patients.

Then there’s a whole subset of moderate-to-severe patients that don’t necessarily have 365 days a year of bad disease. They may have more intermittent disease, two or three months out of the year. And that’s not really a biologic patient in the first place. That’s been a subset of patients who have really suffered without any great treatment options to date. I think Cibinqo becomes a very important addition to our toolbox there and really allows us to treat the patients when they need it and not necessarily have to stay on treatment continuously when they don’t need it.