Examining Newly FDA-Approved Anticoagulants and Upcoming Drugs in the Approval Pipeline

In this episode of Pipeline Projections, Roy Moore—Senior Healthcare Research & Data Analyst at Clarivate and Editorial Board Member of First Report Managed Care—explores newly approved and existing anticoagulant therapies. He analyzes real-world data to inform insurance coverage decisions, offering insights into potential long-term costs and key considerations for both curative and noncurative treatment approaches.

Roy Moore: Hello, everyone. My name is Roy Moore. I'm a senior analyst here at Clarivate. I have nearly 20 years of experience in US and global market access on both market research and consulting services, working across a number of different therapeutic areas and many diseases. So, I think I can speak well to the topics today.

The FDA approved Hympavzi (marstacimab-hncq) on October 11, 2024. Can you provide your perspective on its demonstrated efficacy, particularly in reducing annualized bleeding rates compared to traditional therapies?

Moore: The approval of this drug is quite interesting. One, because it treats both hemophilia A and B, that's obviously a positive, and it has shown efficacy in reducing internalized bleeding rates by I think around 32%. Now, that is the challenge when you're looking at the data because it's actually against mixed comparators. You're not actually doing a head-to-head comparison, which makes interpreting the data a little bit of a challenge.

I would say that the payers who will be looking at this data are also going to be looking at it for hemophilia A and B, and the market is different for both diseases. In hemophilia A, you have factor replacement therapy, as you always had, but you did have the rise of Hemlibra, which was approved by the US Food and Drug Administration (FDA) in 2017. That's actually been a game changer for the market, mostly because it is subcutaneous administration vs something that's physician-administered via IV. Hemophilia B is a smaller population; however, you do have lower rates of resistance or inhibition, but you only have the factors there, so there's actually a better opportunity for this drug there.

That being said, I did speak with our therapy analyst, who is an expert on the hemophilia market, and although the data is promising within hemophilia A, it doesn't look like it's that much better than what you'd see with Hemlibra. It may face some challenges there, even though it does show promising uptake, just because it's hard to interpret the data without an active comparator, or at least a head-to-head comparator.

What advantages does Hympavzi offer in terms of administration and patient adherence compared to existing hemophilia therapies?

Moore: The current treatments for hemophilia, as I mentioned before, typically involve factor replacement therapy, which are IV drugs that are physician-administered multiple times a week. What that means is that patients have to go into the doctor's office and receive that drug multiple times a week. Patients typically don’t like that because it’s obviously an inconvenience. Additionally, it can drive up drug costs because these drugs are physician-administered.

One of the benefits of Hympavzi is that it’s self-administered and it comes in a pre-filled syringe. So, it's subcutaneous and the patient can administer the drug themselves. They do it once weekly, so they're treated less often than the factors, and they can do it themselves instead of having to go to the physician's office. That should drive up adherence. Of course, if you have better adherence, you should be able to reduce downstream costs, such as the need for hospitalizations for lack of adherence, etc. There is less risk of patients developing seizures or mobility issues as well.

How are payers incorporating this data into their formulary decisions, particularly in light of the drug’s potential to reduce long-term health care costs?

Moore: We should say with the current treatments for hemophilia, all of the drugs are reimbursed, according to a Clarivate fingertip analytics product. We actually have a product, where we look at formulary and medical benefit coverage of all drugs and we can segment it by commercial, Medicare, Medicaid, etc.

Within commercial, all of these drugs are reimbursed. It could be under the pharmacy benefit or it could be under the medical benefit. Even though these drugs do have high costs, they are covered, and that's because we're talking about a very small population. There are only around 30 000 to 33 000 Americans who have hemophilia. Payers are willing to accept a higher price because it's a smaller population. That said, they will look at data. When it comes to hemophilia, like with any drug, they do look at a number of factors. We typically segment them into the clinical versus the nonclinical.

In the clinical, they're going to be looking at the analyzed bleeding rate as well as the risk of other bleeding or any kind of any kind of secondary measures such as hospitalization rates, etc. They'll be looking at that, and they will probably look at the data and say, “Okay, it's pretty promising. It's not better than what we already have, but it is promising. The safety and tolerability data pretty good.” They will look at the route of administration. As I mentioned before, it's subcutaneous and self-administered. Payers aren't going to necessarily give you a premium for that, although they do appreciate if it can be self-administered, because it lowers cost for them.

But they have to balance that with the nonclinical factors, and that's basically the cost. We're talking about really high-cost drugs. In the case of Hympavzi, its list price is, I believe, around $800 000. That's a premium over what's already on the market because the manufacturer believes they'll be treating more patients with hemophilia B, which is a smaller population, so they can get a higher price. But they also seem to believe that the ease of administration, as well as the mechanism of action, will be valued by payers.

I will tell you, though, that payers are not going to be swayed by the mechanism of action. They are always going to look at the data. They're going to look at analyzed bleeding rates, and that's going to be top of mind for them. That will be the number one driver, as well as safety and tolerability.

I would say this is an interesting indication because we know there is contracting between manufacturers and payers. Manufacturers will give a rebate back to the payer in exchange for favorable reimbursement. We'll probably see that in the case of Hympavzi.

How does coverage for gene therapies currently on the market, such as Hemgenix, compare coverage for a drug like Hympavzi?

Moore: Hemgenix is on the market. There have been other drugs in pipeline that are gene therapies. They come with a super high price tag if they're approved, millions of dollars, but they're curative. In theory, you pay more because it's curative, you don’t have to worry about it ever again. That said, when it comes to payers, they only have patients on their health plans for a certain number of years. The modeling they do to actually see whether a drug is cost-effective can be tricky because if you're paying $2 million or $3 million for a therapy now and the patient is off your plan in 2 years, someone else is reaping that benefit. That's something of a challenge for payers to address or to wrap their brains around.

How do payers navigate coverage decisions for high-cost drugs, given the frequency with which patients switch insurance plans?

Moore: It would be so much easier if we were in the UK because they can do a cost-effective analysis, lifetime benefit, you're in the same payer, it makes sense economically. It's much harder in the US when patients switch plans every few years, and through no fault of their own, their employer just decides to change plans.

The payers have to balance that, and you do see that a lot with how drugs are covered. If the benefit is longer term, how do they decide to cover it? You see that with some cancer drugs, etc.

How do payers remain competitive in the market when curative treatments or factor inhibitor drugs like the newly-approved Hympavzi become available?

Moore: When you have curative drugs, they want to cover the drugs. First of all, the patient populations for these are pretty small unless you're a small plan, like if you're UnitedHealthcare, or you're a former Anthem plan, or even a statewide Blue Cross plan, you can absorb these costs, because you may only have 3 or 4 patients that are actually on that drug.

You can absorb the costs, and, honestly, if you don't cover the drug, you can actually get negative public feedback. If the public finds out that you're not covering a specific drug, particularly if it's a very high unmet need population, like those with hemophilia, you can get blowback for it. There are often times when even state and federal regulations say you have to cover these drugs. They have to bake that in.

What they can do is try to minimize the cost. That is typically through formulary coverage or utilization management, where they'll say, “Okay, we will favor this specific drug over the other ones for this disease, and we're going to do that through step therapy.” They'll pick that drug based on, obviously, the safety, efficacy, and tolerability, but there is contracting. We see that especially in hemophilia, where the payer will say, “We will reimburse your drug. Fine, we'll even ease up the restrictions, but you have to rebate us back 10% to 15% just so that we can make the numbers work.” Everyone comes away a winner on this. That's how the payers compete. They will agree to cover the drugs, but they will try to limit access in certain ways to steer utilization toward a preferred agent.

Are there any obstacles patients with hemophilia should anticipate, given the need for cost-saving measures like rebates and the condition’s small patient population?

Moore: We do syndicated research on specific diseases, and we have looked into hemophilia. Looking at it now, it is prior authorization, usually to the label. In the case of Hympavzi they're going to say, “Okay, it can only be patients without the inhibitors.” That automatically limits the population there.

We do see some step therapy, as we've seen in the past. Sometimes they will do mandatory specialty pharmacy. What that means is that the physician who gets these drugs has to go through the payer's specialty pharmacy to acquire them. What that does is it limits costs because the physician is not getting the drug via buy and bill and charging more to the payer to administer the drug or just to treat the patient.

So, there are certain methods that they're doing to reduce costs, but I would not call it actively managed. I would say probably managed to the label, at this point, and then use a specialty pharmacy.

How does Hympavzi’s novel mechanism of action influence payer decisions on formulary placement and tiering, or do payers prioritize data over innovation?

Moore: When I've done payer interviews in the past, usually launching new drugs and trying to set the price for it, we would talk to them and say “Okay, here's this novel mechanism of action.” And they will say, “That is nice. We don't care. We don't pay for mechanisms of action.” This is mostly because the payers themselves are pharmacy and medical directors. They're not going to be experts in that disease. They will have KOLs that they rely upon, but they're not going to be experts in disease.

So, they hear a mechanism of action and they're thinking “That’s nice for science, but what does the data actually say?” They're not going to value a new mechanism of action unless it has demonstrated better efficacy, safety, tolerability, or a lower cost.

What I would say in the case of a drug like Hympavzi, when you have a novel mechanism of action and you have a small population, this is screaming out for sort of real-world data analysis, real-world evidence generation contracted with the payers, so we can show that this mechanism of action actually does translate to better outcomes. With the clinical data from the trial, you're talking about a basket of comparators already, you have a small population, and you have a smaller population when talking about head-to-head versus different competitors.

If you can do some sort of real-world data and evidence generation, you can demonstrate that your drug is better. Then you can actually command that higher price, because the drug is priced at a premium to what's on the market.

What do you see happening in the FDA pipeline regarding hemophilia treatments in 2025?

Moore: There were drugs in the pipeline that, when I spoke with our therapy analysts and experts in hemophilia, did seem promising. There should be a lot of activity around this. I am curious to see what happens to gene therapies because that is what you want, you want a curative treatment. I will be curious if they can expand that and how those get taken up, because obviously there is definitely a need for curative treatment within hemophilia. It's a patient population with a high disease burden and a great level of unmet need. It will be interesting to watch going forward.