Emerging Therapies Reshaping Atopic Dermatitis Care
Key Takeaways:
- The atopic dermatitis landscape has rapidly evolved from a minimally managed space to a highly competitive market driven by biologics, Janus kinase (JAK) inhibitors, and newer mechanisms such as interleukin (IL) and PDE4 inhibitors.
- Dupixent (dupilumab) remains the dominant standard of care, creating significant access and differentiation challenges for emerging therapies.
- Payers prioritize strong efficacy data and competitive pricing, with contracting and rebate strategies playing a critical role in formulary positioning.
In this interview, Roy Moore of Clarivate’s market access team examines the transformation of the atopic dermatitis treatment landscape. He discusses the growing pipeline of therapies, including IL inhibitors, JAK inhibitors, and emerging mechanisms, as well as the implications for payers and manufacturers. Moore also explores the increasing role of competition, contracting pressures, and the challenges new entrants face in a market anchored by established biologics.
Please introduce yourself by stating your name, title, and any relevant experience you’d like to share.
Roy Moore: Thank you for having me. My name is Roy Moore. I'm on the therapy team here at Clarivate. I have 20 years of experience in US and global market access across a variety of therapeutic areas, including immunology. This work extends to interviewing payers and doing analysis around the market access landscape for different diseases. Last year, my work on atopic dermatitis included interviews with payers about reimbursement and how that landscape is going to evolve over the next coming years.
Let’s start with an overview—what does the current atopic dermatitis pipeline look like, and which therapeutic classes or mechanisms of action are generating the most momentum right now, particularly among biologics, Interleukin (IL) inhibitors, and Janus kinase (JAK) inhibitors?
Moore: When we think of the landscape and what's in the pipeline, we need to take a step back and see how things have been in recent years. Atopic dermatitis is one of the most dynamic diseases that we've seen in the last several years. A payer I spoke with last year said that several years ago patients were using a lot of creams and methotrexate. It was not a very heavily managed disease state, but that has changed considerably.
We've seen the launch of new therapies across a lot of different therapeutic areas. These include interleukin (IL) inhibitors, JAK inhibitors, PDE4 inhibitors, and other drug classes. There are a robust number of drugs that are currently available that are fighting for market supremacy. That said, it is a dynamic space and we do foresee the launch of more drugs.
The pipeline remains robust. Earlier this year there was an approval, but we are seeing some movement going forward, particularly around the OX40 inhibitors. We have a couple of products in development that we're keeping an eye on that could represent intriguing additions to the pipeline.
Are there any mid- to late-stage candidates or recent FDA approvals that stand out in terms of efficacy, safety, dosing convenience, or novel targeting pathways? Additionally, what upcoming FDA decisions or regulatory milestones should payers be watching closely over the next 12 to 24 months?
Moore: We've seen a lot of activity around atopic dermatitis in specific drug classes, most notably, IL inhibitors. This class is important because they suppress interleukins, which are responsible for the chronic inflammation associated with atopic dermatitis. We've seen activities in development there, including Nemluvio (nemolizumab-ilto), which is an IL-31 inhibitor. This drug class includes Dupixent, which is a combination IL inhibitor that is top of market.
But there are opportunities for other therapies. Difamilast, a topical PDE4 inhibitor, was approved last month. This is an option for patients who do not want to take Eucrisa (crisaborole) or want an alternative to that therapy. However, when it comes to the pipeline, the most active interesting area will be the OX40 inhibitor class, specifically rocatinlimab and amlitelimab.
With increasing competition between IL inhibitors and JAK inhibitors—and the anticipated introduction of biosimilars in this space—how do you see the competitive landscape evolving? How might biosimilar entry affect contracting strategies, formulary positioning, and step therapy requirements within commercial and Medicare plans?
Moore: The market access environment for atopic dermatitis has changed over the last several years. As I mentioned earlier, it transitioned from fairly hands-off management to something far more competitive. This is because several new drugs have increased competition across classes.
Atopic dermatitis fits within the archetype that we consider heavily contracted areas. IL inhibitors—led by Dupixent—are in this area. Dupixent has referential reimbursement due to widespread contracting. Also, because it is the market leader it is considered the standard of care by both physicians and payers.
Additional therapies will be launched, which will increase the demand for contracting to have a parity to Dupixent. To have better placement or better use of a newer therapy, there needs to be better data or at least better reimbursement. This will be difficult to accomplish when Dupixent is already the market-dominant player.
Biosimilars will not have a significant role for several years. The competitive landscape will be pretty static for biosimilars because the existing therapies are competing against each other along with some of the newer agents.
Currently, there is a default payer policy where they reimburse emerging therapies. In fact, they will probably reimburse all these therapies. It depends on how often they'll be used and what line of therapy will be used. This will continue to evolve.
Dupixent can be a deterrent for emerging therapies and other therapies, particularly since a lot of the clinical trial design for these therapies are not built toward superiority. Instead, they're built towards either non-inferiority or at least as indirect comparison with Dupixent. This creates a challenge in both the minds of payers and physicians.
From a managed care perspective, what types of data will be most critical as new atopic dermatitis therapies move through the pipeline—clinical endpoints (eg, EASI scores, itch reduction), safety signals, long-term durability, steroid-sparing data, real-world evidence, or cost-effectiveness models?
Moore: To start, we need to consider that atopic dermatitis is not an indication that has a high rate of hospitalization. So, when payers are looking at this disease and the drugs treating it, they're looking at basic efficacy data as well as cost data. The efficacy data typically includes skin clearance and higher efficacy, particularly for patients with severe disease.
We're also looking for data on better itching and scaling and pain. Data on faster onset of action is also great to have. At the end of the day, it's going to come down to efficacy. In fact, one of the payers I interviewed last year coined it well. He said, “It's efficacy, efficacy, and efficacy. When we're done with that, we'll look at efficacy again.”
When looking at data, payers will generally default to the US Food and Drug Administration (FDA) standard. If it's clinically accepted by the FDA and within the physician community, they will look at that.
There are many different measurements and different outcomes for atopic dermatitis that can be examined at different angles. Payers want to compare these emerging therapies to Dupixent because there is not going to be a head-to-head trial in any case.
I’ve looked at the trial design for some of the emerging therapies, and they tend to still be placebo controlled. They are looking at indirect evidence. As I said, there is not a significant risk of hospitalization for atopic dermatitis. If there were, the payers would be receptive to some data showing that a new/different drug can affect that. However, that’s not going to be the case.
Real-World Data
When it comes to real-world data for atopic dermatitis, payers have told me that they are skeptical. The reason is that they typically have 3 criteria: The data has to be relevant, it has to be easily obtained, and it has to be meaningful. In the case of atopic dermatitis, EASI-75 is a relevant data point, but it’s not something that is always captured by the clinician. So, real-world data will have limited import because it won't necessarily have the amount of data needed. Instead, payers will look at guidelines.
For a manufacturer, I'd be trying to generate additional data. However, in order to affect guidelines and impact payers, it is best to have the data published in journals because payers can look at a peer-reviewed journal they can trust and know that it's not biased by the manufacturer itself.
Safety
When I spoke with payers, treatment safety is a concern. Adverse events (AEs) are divided into 4 levels. Levels 3 and 4 are the most severe and require hospitalization. However, in the case of atopic dermatitis, payers I spoke with were also interested in the lower levels (1 and 2). This is not because they think that those adverse events are significant medical issues. Rather, those AEs could be annoyances to the patient, and those annoyances could lead to noncompliance, which could lead to abandonment of therapy.
So, when it comes to safety, I would also make sure to capture data from all different levels because payers want that level of granularity. They want data on the long-term durability as well (more than 6 or 9 months). They want to know how well the drug works in the long term, at least 1 year, maybe 2 years if possible.
Cost-Effectiveness
As far as cost-effectiveness models are concerned, payers have told me they're not going to do a cost-per-quality model for atopic dermatitis. They're going to line up one drug against Dupixent. They're going to eyeball it. The new drug will probably be placebo-controlled, so payers will do an indirect comparison and try to see if there are any areas where the drug is better or if at least it's going to be non-inferior to Dupixent.
If the drug is non-inferior, then it will come down to a pricing game. Dupixent already has robust uptake and widespread formulary reimbursement as a preferred agent. So, payers are going to be looking for price cuts around net pricing. That harkens back to the need for contracting for better rebates for payers.
What do you anticipate will be the biggest access challenges over the next 5 to 10 years—particularly as more premium biologics and oral agents enter the market?
Roy Moore: The biggest challenge is the entrenched powerhouse that is Dupixent. As I said earlier, we went from an unmanaged space to an increasingly managed one because of high-cost drugs that have moved into the market. The demand transitioned from low-cost creams and methotrexate in favor of biologics and JAK inhibitors. As a result, more expensive drugs require more management.
Out of this maelstrom of new therapies and launches came Dupixent, which benefits from strong efficacy across many diseases, a broad FDA label that allows it to compete in a lot of different diseases, and that leads to contracting. This allows Dupixent to be a preferred agent from the payer perspective. It's a lot easier to contract with 1 drug across many different diseases and get a bigger rebate than it is to negotiate with a lot of different drugs.
The biggest challenge tied to that is how to compete with Dupixent. The trials are built around placebo control, so what would come of a head-to-head trial? What if the drug doesn't measure up? As a result, indirect comparisons are made, which doesn't allow payers to see if a new drug is better than what is already available. This is why they're interested in real-world data, if it exists.
Without better clinical data, it's going to come down to net pricing. Manufacturers will need to offer better rebates or better discounts or some other services that will be meaningful to payers to give them preferential treatment or to physicians who have the freedom to choose their preferred drug.
