How Fitusiran Changes the Treatment Landscape in Hemophilia: Guy Young, MD

Fitusiran (Qfitlia; Sanofi) was approved by the FDA as subcutaneous prophylaxis for patients with hemophilia A or B with or without factor VIII or IX inhibitors in March. The interference RNA therapeutic demonstrated low bleed rates across patient subgroups with as few as 6 injections a year in the phase 3 trials submitted with the new drug application.

ATLAS trial investigator Guy Young, MD, a pediatric hematologist at Children's Hospital Los Angeles and a professor of pediatrics at the University of Southern California Keck School of Medicine, joined The American Journal of Managed Care® to discuss the current treatment options physicians have for their patients with hemophilia A or B, with or without inhibitors, since the FDA approval of fitusiran earlier this year.

This transcript has been lightly edited; captions were auto-generated.

Transcript

How does the FDA approval of fitusiran impact the treatment landscape for patients with either hemophilia A or B?

Fitusiran was licensed at the end of March in the United States for patients older than 12 with hemophilia A or B, with or without inhibitors. As far as the landscape is concerned, for patients with hemophilia B—let's talk about those with inhibitors—there's only one other medication that is approved and effective at controlling bleeding in those patients, which is concizumab, which was licensed just a couple of months before fitusiran. Concizumab is given as a daily subcutaneous injection. It has a one-time, at least, required laboratory test to check the level.

Fitusiran starts as a once-every-2-month subcutaneous injection. It does have required labs once per month because the level of antithrombin, which is the pharmacodynamic marker of fitusiran—the way fitusiran works is by lowering antithrombin—we have to keep the level between 15% and 35%, and for that reason, there are labs required once a month using an FDA-cleared antithrombin assay, which is available commercially in many labs, although some labs won't have that specific assay. Then, there's a program through Sanofi that patients can get labs drawn through a program through LabCorp. Essentially, those are the 2 drugs available for patients with hemophilia B with inhibitors for bleed prevention.

Fitusiran, being [administered] every 2 months, may be an option that might be preferred over one that is given subcutaneously every day. Although, again, concizumab has shown really good results as well. There's certainly nothing wrong with treating a patient with hemophilia B with inhibitors with concizumab.

For patients with hemophilia B without inhibitors, factor therapy is still available, of course. Most patients use extended half-life factor products, and typically the doses are once a week, although it could be somewhat less often than that, but those are all given intravenously, so there's always that particular challenge. Not every patient has great venous access. It takes fairly long—10, 15, 20 minutes—to do the infusion, and it does create problems with adherence.

The subcutaneous options, again: in this case, fitusiran is approved for this use in patients without inhibitors. Concizumab, at this point, is not yet approved for patients without inhibitors, though that may be coming soon. There is another drug, marstacimab, that is approved as a subcutaneous drug for bleed prevention in patients with hemophilia B without inhibitors. That one is given once a week subcutaneously, and there's no lab requirement with that.

For patients with hemophilia B without inhibitors, their options are to continue IV [intravenous] factor therapy—although many are going to want a subcutaneous option—and then fitusiran is the every-2-months option. Some patients may need to dose every month, but most will stay on every 2 months. And then there's marstacimab, which is given weekly, and there's no lab monitoring required with that one.

With respect to hemophilia A and fitusiran, we have to discuss the fact that there are other treatment options in hemophilia A that don't exist in hemophilia B, and of course, that is emicizumab [Hemlibra], and emicizumab has been available for 8 years. It is given subcutaneously, either weekly, every 2 weeks, or every 4 weeks, and it has become the No. 1 option for patients with hemophilia A, with or without inhibitors, for bleed prevention. So, the question becomes, what does fitusiran offer that Hemlibra perhaps doesn't offer?

Let's start with a few rare situations. There are rare patients, and I say rare, I mean really rare patients, who have antidrug antibodies to emicizumab, essentially like an inhibitor to emicizumab, and therefore they can't use it. Those patients, of course, could be good candidates for a drug like fitusiran. Then there's another group of patients I quantify at around 10% that don't seemingly do as well as most other patients with emicizumab. Instead of 0 to 1 bleed a year, they may have 2, 3, or 4 bleeds a year. Often, these are more active patients, and the bleeds are not spontaneous, but activity- or trauma-induced. Then the question becomes, can fitusiran offer a higher level of bleed protection than emicizumab? And I think we don't know that; the jury is out on that.

There are some studies that are looking into that, but for the patient who's not doing so well, of course, they do have the option to go back to IV factor replacement, which may work better for them, but once patients are on subcutaneous therapy, they don't really want to go back to IV. It'll be like going from the iPhone 16 and then saying, “My next iPhone is going to be the iPhone 12.” Nobody wants to go backwards in that way. Then the question is, can they do well with fitusiran, with reducing the number of bleeds that they get per year, including those who are active?

For those who are not active, who are getting multiple bleeds a year on emicizumab, I definitely think that fitusiran is a great option. For those who are active, it's probably worth a try, but I know we don't really have great data yet on how well fitusiran will protect from activity-related bleeds, but if they're not doing well, then that is an option. So, that’s for the 10% of patients who are not doing well with emicizumab.

Lastly, there are the rest of the patients who are doing well. However, emicizumab has to be drawn up in a vial. You have to draw exactly a certain dose for your weight. The volumes tend to be fairly large, especially for bigger people. The every-4-week dosing has a very high volume, so most people don't even use it. Then there's the matter of, well, fitusiran is every 2 months, the volume is 0.5 mL, which is far less than what emicizumab would be. Patients who are doing fine bleedwise, but don't love administering the emicizumab because of the pain or the volume, or they want a less frequent schedule, well, in that case, a discussion about fitusiran could be had with those patients, since the dosing schedule is much less, every 2 months. At most, some patients would need it every month, but it still retains that low volume. So, that's another group of patients worth having a discussion with about [fitusiran].

All in all, I do think most patients on emicizumab who have been on it for years, who are comfortable with it, probably aren't going to want to switch to fitusiran if they're doing well, but I think some might be interested. The last aspect is that fitusiran comes in a neat little pen, so it's a disposable, one-time use pen, very, very simple to use, as opposed to the administration option that's available currently for emicizumab. So, that's for hemophilia A, and that would include patients with and without inhibitors. Right now [fitusiran] is only for patients older than 12, anyway, so in terms of the landscape, that's my summary about where fitusiran fits in with the other available options.