Redefining Asthma Management With Emerging Anti-Inflammatories

Roy Moore, a market access expert, discusses the evolving asthma drug pipeline, highlighting upcoming therapies—including Breztri, depemokimab, and masitinib—their potential to improve adherence and outcomes, payer considerations around cost and generics, and the importance of linking clinical evidence to reduced medical costs to secure favorable coverage in the next 5 to 10 years.

Roy Moore: My name is Roy Moore. I've got close to 20 years of experience in global and US market access, including syndicated and consulting projects. I interview payers to understand how the reimbursement landscape for drugs is coming along and summarize those conversations for reports that we put out that are always disease specific.

Let’s start with an overview—what’s the current landscape of anti-inflammatory therapies in the asthma drug pipeline, and what mechanisms of action are generating the most attention?

Moore: Asthma, of course, is a very interesting disease because you have a fairly heterogeneous population and, as a result, you tend to have different mechanisms of action (MOAs) at play because you're trying to attack the disease in different ways.

The current state is that we have a set of MOAs that include inhaled corticosteroids (ICS), long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), leukotriene inhibitors, and then combinations of the above. That could be a LABA/LAMA/ICS or anything of that nature.

Of course, we do have biologics that are available. Those are the monoclonal antibodies. Those are usually for a case of severe asthma. It's a pretty robust pipeline and a pretty robust market, as it stands. A lot of these drugs have been in the market for quite a long time, so they've gone generic. You have a landscape where payers are reimbursing the generic versions of the drugs. The branded versions are not being reimbursed, they are just left off formulary. But those that don't have generic equivalents are going to be reimbursed, and oftentimes on a preferred tier, which means patients are able to access them for a copay. Now, the biologics will typically be covered under a specialty tier or under medical benefit, in which case beneficiaries will be paying co-insurance. That net set is a percentage of the list price.

Are there any candidates in mid- to late-stage development stand out in terms of efficacy, safety, or differentiation, and how might they reshape treatment paradigms?

Moore: There are 3 drugs right now that we're anticipating getting approved starting next year. One is Breztri. It's actually a drug that's already approved for chronic obstructive pulmonary disease (COPD). It's a combination therapy. It's a LABA/LAMA/ICS. As far as this drug, we know it's out there, so we have some data on it. There's nothing that stands out about it except that we do know in clinical trials they are looking at recruiting adolescents. You're looking at a population that usually doesn't get covered in these trials because, typically, it's adults. That is something that will be intriguing. We'll see how those results turn out and, of course, how they're reimbursed. The drug is covered because it's already available for COPD.

There is actually a little more excitement, though, in other classes. GSK has a long-acting IL-5 inhibitor called depemokimab. It's in phase 3 trials right now. What's interesting about this is that it's subcutaneous and it's administered every 6 months.

Let's compare that with what's currently on the market. Cinqair is every 4 weeks while Fasenra is every 8 weeks. From a physician and payer standpoint, the idea that the timing for treatment is going to be fewer, that means you're probably going to have greater compliance because, obviously, there are times where you wouldn't be taking the drug. That's really promising and that's coming out next year.

Lastly, there's masitinib. That's AB Science's twice daily oral therapy. It's a TKI. It has a lot of promise because it's going after a certain population with uncontrolled severe asthma, and there aren't a lot treatments for that. However, it's a TKI, so the side effects may give pause to payers in some cases. We'll see how those shake out.

As far as how they reshape the paradigm, they'll just be additional options. Payers do like when there is a new drug class because it gives physicians greater options to treat patients who are edge cases or not served by current treatments.

How could emerging therapies influence the positioning of existing treatments—particularly inhaled corticosteroids and currently available biologics?

Moore: Emerging therapies are going to run into an issue, and that is that you have treatments already available. They've been on the market a long time and a lot of times they've gone generic.

That creates a cost anchor in the eyes of payers. They say, "Why should I cover this drug on a favorable tier when I can get this other drug that is a different class, or even the same class, that is generic and cost me pennies on the dollar?" They have to find their niche.

Let's look at the case of masitinib. That's the TKI that I mentioned. It's an oral therapy. It actually might have some influence on what's currently on the market, mostly because it's going to be lower cost. It might be used in front of the biologics because it'll have a much lower cost.

For the LABA/LAMA/ICS, like I said, it's already approved, so there's not really much you could see there with that affecting the current treatment. Again, this is a very competitive space, and you do have a lot of contracting already in place. Manufacturers are already giving rebates back to payers for favorable coverage.

With the monoclonal antibody from GSK that's coming out, it'll be another option. How I can see that affecting things is that those drugs are typically already covered under specialty tier or under medical benefit. You could see an influence on rebates going up, perhaps. You could see payers eventually favoring one therapy over another, but I don't think it's really going to happen because they want to give physicians options, and they don't want to necessarily drive behavior unless it's mandated or required by the organizations like the broader physician community.

What data points—clinical, safety, biomarker, or cost-effectiveness—should providers and payers be watching most closely as these therapies advance?

Moore: That's a great question. They probably won't be looking at cost effectiveness because it takes a lot of time to do that data. How is it really usable in their mind? What they're typically going to focus on is going to be the clinical data, the efficacy, and the safety. They'll be looking, of course, at the FEV1, but the big one they'll be looking at is the rate of severe exacerbations. The reason that's important is if you're a patient with asthma and you have a severe exacerbation, there's a chance you can end up in the emergency room (ER) or even in the hospital. That's top of mind for the payers because that does add cost to them. That's something that they will be looking at.

The challenge is that they would like for that data to link to medical costs. In fact, when I talk to payers—and I was actually talking to them earlier this year for COPD, which is a related disease—that’s what they said: "We want to see the exacerbations come down, but to be truly meaningful, it has to be connected to reducing costs, particularly medical costs." That's something that they'll be looking at.

The other data points, again, I mentioned that some of these drugs are administered less often. If that has an impact on adherence, that is something they would be looking at. That's something that the manufacturers should be capturing.

I would definitely recommend that any of the manufacturers who are coming out with therapies that evidence generation doesn't stop at US Food and Drug Administration (FDA) approval. You want to do phase 4 trials, particularly if you can track adherence and you can tie that to medical costs because that is going to be something that's going to be useful and actionable for payers.

What are the biggest challenges to integrating newer anti-inflammatories into care pathways, and what does the next 5 to 10 years of innovation look like in this space?

Moore: That's a great question. You will continue to see, obviously, more drugs coming out in all these different classes because there's going to be iteration on the part of manufacturers.

Payers do want to see MOA. As I mentioned before, asthma can be a fairly heterogeneous population, so they need different tools in the toolkit, essentially. They're going to want those. That's something that they'll be looking forward to.

The biggest challenge though is, again, this is an indication where a lot of the drugs have gone generic and they are effective. They're trusted by physicians and payers. Payers may not be super excited to update their formularies to incorporate a very expensive therapy if it doesn't show superiority to what's on the market that's already fairly inexpensive. That's going to be the biggest challenge. For the manufacturer, the way you handle that is, obviously, the guidelines, but for the relevant bodies—and in asthma that's the case.

You want to make sure that you can generate additional evidence and make sure those guidelines include your therapy. That's one thing that the payers will listen to, because a physician saying to a payer, "I want this drug, and it's in the guidelines,” will probably make the payer receptive. That would be my advice for this space.

Is there anything else that you would like audiences to take away from this?

Moore: It's a fascinating disease. Obviously, hospitalization is going to be something that's key. Reducing exacerbations is going to remain key. We'll see what new drug class is coming out and how they can affect this population. It'll be exciting in the next 5 to 10 years.