Management of Acquired Thrombotic Thrombocytopenic Purpura (aTTP) - Episode 4

Using Caplacizumab to Treat Acquired TTP

An expert in acquired TTP describes the use of caplacizumab in treating acquired TTP, and highlights data from a phase III clinical trial.

X. Long Zheng, MD, PhD: Now we can talk about caplacizumab. Caplacizumab is a humanized monoclonal antibody that initially was identified or isolated from a llama. It’s a single chain monoclonal antibody and is specifically targeted at von Willebrand factor. So this monoclonal antibody inhibits von Willebrand factor and the platelet interaction. By doing that, you break up or prevent thrombosis, or ongoing thrombosis, in patients with TTP [thrombotic thrombocytopenic purpura], despite that they don’t have ADAMTS13 to cleave them. If they can’t stick together so you actually prevent thrombus formation. Caplacizumab is the only FDA [Food and Drug Administration] approved drug thus far for treating acquired TTP. So the phase III double-blind controlled trial shows that if you add in caplacizumab, the primary end point, which is looking at the time for platelet normalization, is actually significantly improved. So it shortened the time needed for platelets to be normalized. Then there’s also several other secondary end points, which is also showing the rate of thromboembolism and some other mortality. The composite end point is also significantly reduced as well. How do you use caplacizumab? Caplacizumab is approved for the adult TTP patient either in the first episode or during the relapse. It’s actually given for the first day, 15 minutes before plasma exchange, and then after plasma exchange is completed you give another dose which is 11 milligram subcutaneous after the plasma exchange. Before plasma exchange it’s actually given intravenous infusion. And then subsequently you give caplacizumab every day subcutaneous after completion of the daily plasma exchange, until the platelet count is normalized, which means the platelet count reaches 150,000 per microliter. At this point, the plasma exchange can be stopped, but the caplacizumab continues for another 30 days. And, if necessary, if we need it, let’s say this patient after 30 days, if the ADAMTS13 still measures low, you can actually go on for another 28 days of so-called extension. So that’s how you currently use caplacizumab. Caplacizumab is actually used in conjunction with plasma exchange, corticosteroids, and rituximab.

Caplacizumab, as I just mentioned, actually prevents von Willebrand factor platelet interaction and transformation. But this is not targeting the etiology, which is the autoantibody formation. So you need to inhibit the immune system so that you don’t actually continue [to] produce the antibody against ADAMTS13. Rituximab is a monoclonal antibody against B cell CD20. So, you bind to B cell, which is a cause of B cell deaths. Then the B cell is the one that go on [to] become a plasma cell making the antibody. So rituximab in combination with corticosteroids will inhibit immune system so they’re not producing antibodies. This is really important. When you treat the patient with plasma exchange and caplacizumab, you always want to at the same time suppress the immune system so they’re not making ADAMTS13 antibody. If you don’t do that, the moment you stop plasma exchange or caplacizumab, the patient’s disease will recur. So suppressing antibody production is extremely important. The rituximab does this.

Transcript edited for clarity.