Many patients with moderate to severe atopic dermatitis have poorly controlled disease. These patients can experience skin trauma, intense itching, sleep disturbances, secondary effects like anxiety and depression and significantly diminished quality of life.3, 4
Mild cases of atopic dermatitis are frequently treated with a topical corticosteroid or emollient skin creams or ointments. Unfortunately, long-term use of topical steroids can cause thinning skin, atrophy, acne and disfiguring changes in skin pigmentation.5
Moderate to severe atopic dermatitis may need to be treated with medications that affect the immune system (immunosuppressants). Historically these have included off-label use of drugs like methotrexate, azathioprine, and cyclosporine. These can have serious side effects and are only recommended for short-term use.6
More recently Dupixent® (dupilumab) has replaced the immunosuppressants for moderate-to-severe patients. Dupixent is a biologic drug. It is considered the current market leader mainly because of its good safety profile, especially for chronic use. Dupixent does have some drawbacks, including being an injectable, as well as high cost. The Wholesale Acquisition Cost (WAC) for Dupixent is approximately $41,000 per year.7
Let’s review some of the drug development activity in this dynamic space.
We can sort the next-gen options to treat atopic dermatitis into two basic buckets. One bucket contains biologic drugs like Dupixent called interleukin (IL) inhibitors. The other contains small molecule drugs called Janus kinase (JAK) inhibitors.8
IL and JAK enzymes are part of the same basic immune system signaling process (the JAK-STAT pathway). They are particularly important in immune responses and diseases like atopic dermatitis.9
Inhibitor drugs that target IL and JAK enzymes are both attempting to influence the signaling pathway; they just act on different parts of the pathway. But from a pharmacology perspective, the drugs are quite different.10
There are at least three new IL inhibitors under development for atopic dermatitis. They include tralokinumab (reviewed here), plus nemolizumab and lebrikizumab. Tralokinumab has been delayed from its scheduled approval date in April of this year due to questions about the device used to administer the drug.11 Lebrikizumab’s Phase 3 trial was suspended in 2020 due to COVID-19.12
There are four JAK inhibitors that are expected to be approved this year (abrocitinib, ruxolitinib, baricitinib, upadacitinib). Some of these products are already available for other uses but are now under Food and Drug Administration (FDA) review for atopic dermatitis. You can read our review here. In addition to these, there may be at least four additional JAK inhibitors evaluated by the FDA within the next five years.13
There is additional development activity, including non-JAK small molecules and different monoclonal antibodies. However, the main activity seems to be concentrated in the two buckets described above.14, 15
Sorting the market
We are probably not looking at a winner-take-all scenario in favor of either the biologics or the JAK inhibitors. There are clear differences in mode of action, safety, route of administration and price among all of the new drugs in the pipeline. All of these factors will be important.16
Dermatologists must weigh all the available options for each patient based on their specific situation. This includes the choice of biologics versus JAK inhibitors.
We may see a blend of products, not only among patients, but for individual patients. Each mix will be designed to address different levels of disease severity and use multiple approaches in order to care for a diverse patient population.17
And we should caution that there are still many important questions the next wave of atopic dermatitis agents. For example, concerns about JAK inhibitor safety, like off-target effects, plague the entire class. These concerns remain valid for atopic dermatitis as well.18
We cannot say for sure that a particular developmental drug will actually come to market, including the ones mentioned in this report. But analysts expect the atopic dermatitis market to grow faster than other leading dermatological conditions such as psoriasis and psoriatic arthritis in the coming decade.19 As noted above, in dollar terms the global atopic dermatitis market may reach approximately $20 billion by 2027.20
In general, small molecule drugs are much less expensive than biologic drugs. So while the overall size of the atopic dermatitis market will grow, the exact mix of utilization between the biologic and small molecule atopic dermatitis drugs will matter a lot, although perhaps not immediately.21
For example, we should not necessarily assume that the small molecule JAK inhibitors will be less costly than an existing biologic like Dupixent, at least at first. In fact, the JAK inhibitors currently approved for other conditions such as rheumatoid arthritis are actually more expensive than Dupixent.22
That could change over time. One reason is that atopic dermatitis has a far larger patient population than rheumatoid arthritis. And analysts forecast 11 new product launches for atopic dermatitis globally between 2020 and 2029.23
Since multiple offerings in the same drug class tend to yield lower prices, the market for JAK inhibitors may evolve to look very different for atopic dermatitis in the coming years.
There is still more work ahead. One broad unmet need is treatments for children.
As noted, there are roughly three million children in the U.S. with moderate to severe atopic dermatitis. Until relatively recently, there were no systemic drugs, other than corticosteroids, approved for pediatric and adolescent atopic dermatitis24 Dupixent was approved for adults in 2017, and then received approval to treat adolescents (age 12+) in 2019. Use for children aged six and up was approved in 2020. Studies are also underway to evaluate Dupixent for younger children.25
Additional studies are underway to learn about whether any of the potential new treatments may prove useful for younger patients.23
The biggest remaining challenge in atopic dermatitis is to move beyond just treating symptoms and into disease modification. That is, therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic disease.
Theoretically the biologics have the potential to act as disease modifying drugs. Researchers are investigating various types of the interleukin molecule (found in tralokinumab, lebrikizumab and nemolizumab). These have the advantage of blocking multiple steps of the inflammation cycle that causes atopic dermatitis. The hope is that drugs in this class may offer both a rapid and durable therapeutic response.26
What remains is to build up our experience and our understanding of how all these molecules work and gather the data to determine which approaches work best for patients. Only then can we determine whether they can do the job of switching off the disease.27
Health care providers are excited by the possibilities that a more diversified atopic dermatitis drug class may hold for their patients. However, it is reasonable to expect overall spending in the class to rise as multiple new drugs enter the market and as the atopic dermatitis population grows.
Plan sponsors can look to Optum Rx for ongoing updates as new drugs make their way through the development pipeline. And as always, you can count on Optum Rx for the resources, programs and clinical assistance you may need to manage these new medications effectively.