New FDA Approval: Bevyxxa
Extended duration Venous thromboembolism (VTE) prophylaxis in hospitalized adult patients at risk for thromboembolic complications secondary to immobility or other risk factors.
The indication is limited to patients without a prosthetic heart valve (betrixaban has not been studied in this population).
How it Works
Bevyxxa is a direct Factor Xa inhibitor, similar to the others in its class:
- Rivaroxaban [Xarelto]
- Apixaban [Eliquis]
- Edoxaban [Savaysa]
- Betrixaban [Bevyxxa]
They all work by (wait for it...) inhibiting Factor Xa in your coagulation cascade. You know that monstrosity of a thing that looks like this:
So, you inhibit Factor Xa, you inhibit clotting. Makes perfect sense, right?
Notable Adverse Effects
You may want to sit down for a second, because I'm about to tell you something shocking.
The most notable adverse effect of Bevyxxa (an anticoagulant) is that it can cause bleeding. In the study (the APEX study), the most common reason for discontinuation of Bevyxxa was bleeding (2.4% of Bevyxxa patients compared to 1.2% of enoxaparin patients dropped the study due to bleeding). In particular, Bevyxxa showed twice as many nosebleeds and hematuria compared to enoxaparin.
That said, major bleeding events were equal in both treatment arms (and both were less than 1%) The vast majority of major bleeds with Bevyxxa were in the GI tract, so I'd be especially careful in patients with a prior history or with other risk factors for GI bleeds.
As for non-bleeding related adverse events, not much really stands out with Bevyxxa compared to enoxaparin. The rates are all less than 5%, but they include side effects such as nausea, diarrhea, urinary tract infection, constipation, and hypokalemia.
Otherwise, Bevyxxa is similar to other Xa inhibitors. There is a reduced dose in renal failure (CrCl < 30 ml/min) and in patients on P-gp inhibitors. If the patient has both renal failure and is taking a P-gp inhibitor, you should avoid Bevyxxa. Bevyxxa wasn't studied in liver failure (as many anticoagulants aren't) because of the inherent coagulopathies seen in that patient population.
Current Place in Therapy
So what need are we really satisfying with Bevyxxa? There are patients with acute medical illness (i.e. exacerbations of heart failure, stroke, and infections [especially pulmonary infections such as pneumonia]) that severely limit the patient's ability to move around. During this period of immobility, they are at risk for developing VTEs.
While in the hospital they're given enoxaparin. But then the patients go home and VTE prophylaxis is stopped. Unfortunately, the patient is often just as immobile (or only slightly better) in the first weeks after they leave the hospital.
So (at least in my mind), part of what the APEX study is looking at is whether extended duration VTE prophylaxis is better than standard prophylaxis of giving enoxaparin while inpatient and maybe for a few extra days outpatient. I've seen it noted somewhere (but I can't seem to find the exact reference) that the majority of all VTE events happen after a patient has been discharged from the hospital.
In that category, Bevyxxa passes with flying colors. It reduced DVTs and PEs by 1.6% (that's absolute risk reduction) compared to enoxaparin. 1.6% may not sound like much, but when you consider there are about 900,000 events per year in the US (according to the CDC) you're talking about quite a reduction in morbidity.
So what exactly is "extended duration?" In the APEX study, Bevyxxa patients were treated for 35 - 42 days compared to enoxaparin's 6 - 14 days. For most of the acute illnesses I mentioned above, patient mobility should be improved after the 5 - 6 week treatment duration of Bevyxxa. The increased bleed risk in the Bevyxxa arm seems kind of intuitive when you account for the longer treatment window in Bevyxxa patients.
In the end it will come down to a patient-specific decision. What is the risk of bleeding compared to the risk of clotting? For patients that are likely to have impaired mobility for several weeks, extended duration VTE prophylaxis seems like a good idea. Bevyxxa presents a convenient PO formulation that overall is very well tolerated for just that purpose (and they don't have to inject themselves in the belly every day like they do with enoxaparin).
It's also worth noting that enoxaparin isn't even approved for extended duration VTE prophylaxis. In fact, Bevyxxa is currently the only thing approved for extended duration prophylaxis. Because it can be started inpatient, it will be easy to transition patients to the outpatient setting to complete their treatment course.
But what about the cost? So far, I haven't been able to find any hard numbers on the expected cost of Bevyxxa. I know that enoxaparin syringes aren't exactly cheap, but Portola pharmaceuticals seems to be going the popular route of pricing the drug by comparing it to the worst possible thing that it could prevent. I'll have to hold my final judgement until I see the eventual price.