In an interview with Pharmacy Times, Robert Harrington, MD, Librexia program chair and Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and Provost for Medical Affairs at Cornell University, discussed the Librexia clinical trial program evaluating milvexian, an investigational oral factor XIa inhibitor. The program includes 3 concurrent clinical trials, investigating milvexian’s use for ischemic stroke, acute coronary syndrome, and atrial fibrillation. All 3 indications received FDA fast track designation in 2023.
Q: How does the fast track designation for milvexian, granted in 2023, push this research forward?
Robert Harrington, MD: It’s impacted less now during the ongoing protocols in the 3 studies—as I said, acute coronary syndrome (ACS), atrial fibrillation (AF), and secondary stroke prevention. And so, all 3 trials are running, they're running concurrently. While running, if we have a protocol amendment, with the fast track designation we get a faster protocol review than we might if it wasn't on the fast track at the end, when we're all done. Let's say, for sake of argument, [if] we have positive results, fast track allows the FDA to move things forward more quickly, because it's a novel first-in-class therapeutic, that it'd be better than the preexisting therapeutics. So, I wouldn't say it does a lot right now. Maybe it gives you a little more of a favorable, quicker look, if you have amendments, etc. But where the advantage may come in is at the end, in terms of hurrying through that review process if the trials are positive.
About the Trials
LIBREXIA-STROKE
Trial Name: A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack
ClinicalTrials.gov ID: NCT05702034
Sponsor: Janssen Research & Development, LLC
Completion Date (Estimated): December 9, 2026
LIBREXIA-ACS
Trial Name: A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome
ClinicalTrials.gov ID: NCT05754957
Sponsor: Janssen Research & Development, LLC
Completion Date (Estimated): October 19, 2026
LIBREXIA-AF
Trial Name: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation
ClinicalTrials.gov ID: NCT05757869
Sponsor: Janssen Research & Development, LLC
Completion Date (Estimated): May 5, 2027
Q: What safety and efficacy data have been gathered thus far from the Librexia clinical program?
Robert Harrington, MD: Oh, yeah, I mean, a lot. So, one of the real interesting parts of these trials is that we're running 3 trials concurrently. I'd say, usually you do one trial, you do another trial, you do the third trial, and you're sort of building the information, and you're building upon what you learned. We decided to do all 3 concurrently, so we have study teams for each of the overall programs. We have a study team made up of experts from the individual programs that oversee the whole thing. We're collecting data using common data definitions across all 3 trials, we’re adjudicating events with the same definitions across all 3 trials, and we have a single independent data safety monitoring board (DSMB) across all 3 trials. So, all 3 trials are exposed to a review at the same time. And so, the DSMB has experts in each of the areas, but they're looking at it from all 3 trials. And I think that's a really unique way of doing studies like this. Let's say for the sake of argument that there's something going on in the AF trial. Well, I think it allows the stroke trial DSMB members to look at the data a little more critically, because AF is essentially a stroke prevention trial. So, they get to look at a little more critically by doing it that way.
We've enrolled close to 10,000 patients by this point across the 3 trials, so, you know, if you were doing just one trial, you wouldn't have all that information. But we're doing 3 trials, you have all this information now to be able to look across the milvexian landscape, if you will.
Q: How has milvexian been investigated both as a monotherapy and in combination with antiplatelet therapy?
Robert Harrington, MD: So, you can get on top of that and you're comparing it to people with placebo, on top of antiplatelet therapy, so you're really comparing the milvexian to placebo. In the total knee replacement study, you're comparing milvexian to enoxaparin, so you're looking to see clot prevention with enoxaparin. So, you’ve got 1200 patients who got milvexian or enoxaparin, so they got either the oral drug or the subcutaneous drug. And then they looked at clot formation, and there was less clot formation with milvexian, particularly the highest doses. So, in that one, you're comparing milvexian to an active anticoagulant, which we know has a benefit compared with placebo.
Q: The phase 2 proof-of-concept data showed benefit with milvexian as both a monotherapy and in combination with antiplatelet therapy. What does this mean for the treatment paradigm, should it be approved?
Robert Harrington, MD: Yeah, great question. I think what it does is, when you're adding it to something, you're getting the placebo comparison. When you're going head-to-head with something, you're raising the question of whether you can replace it. So, let's say for the sake of argument that the trial is positive in ACS. That would mean that clinicians would say, “Okay, my patient’s going to get antiplatelet therapy and now I'm going to add milvexian on top of that.” So, you're going to have an anticoagulant and antiplatelet. In AF, however, we're comparing it directly to apixaban, the Factor Xa inhibitor, and let's say for the sake of argument, it wins, it's better. Then you'd say, for your AF patients, you should treat them with factor XIa inhibitors instead of factor Xa inhibitors. So, I think what I like about the whole program is it gives, I think, at the end of the day we'll have data to allow people to sort through whether or not you want to add Factor XIa inhibitors on top of something else, and whether or not you want to use it instead of Factor Xa inhibitors. And remember how good Factor Xa inhibitors are, I mean, they're like considerably better than warfarin.
Q: What should pharmacists know about the management of milvexian?
Robert Harrington, MD: That like Factor Xa inhibitors, milvexian won't require therapeutic monitoring. That's remains a big thing in comparison to, say, warfarin, where we have to measure the international normalized ratio (INR). And the hypothesis is that we think you can get effective clot prevention while minimizing risk of bleeding. That's probably the most important piece of milvexian is that no monitoring, antithrombotic efficacy, with minimization of bleeding risk. Those would be probably the 3 take-home messages that I would give people, that's why we're doing the study, because those 3 things are really attractive. You don't have to monitor it, it might work, and you won't get as much bleeding.
