Garadacimab, Sebetralstat Were Both Safe to Use in Clinical Trials: Timothy Craig, DO

Timothy Craig, DO, professor at Penn State University and principal investigator of the VANGUARD phase 3 trial (NCT04656418) on garadacimab, discussed the safety profile of garadacimab, which was approved for use in patients with hereditary angioedema (HAE) on June 17, and sebetralstat, which is awaiting FDA approval for use as rescue medication in patients with HAE.

This transcript has been edited for clarity; captions are auto-generated.

Transcript

What is the safety profile of both garadacimab and sebetralstat?

One of the nice things about garadacimab, even though it's on the very top of the coagulation pathway, the 5 analytic pathway, the complement pathway, and the contact or kallikrein pathway, like we were talking about, it really has very good safety. Actually, to prove that, we monitored a variety of things during phases 2 [and] 3 and the open-label [trials], and that was thrombosis and bleeding. There really wasn't any signal that garadacimab, because of inhibition of factor XIIa, that had anything to do with bleed and/or thrombosis, it was very, very clean. The injection site reactions are minimal, and the other adverse effects really were also minimal. So it seems like a really safe medication to use for long-term prophylaxis.

With sebetralstat, also, the adverse effects were minimal. People question, can you take it if you say you have nausea? Are you going to vomit up the medication, since it's an oral medication? It looks like that's not an issue. Also, people ask, "Can you swallow it if you have an obstruction in the throat, if you have an attack in the throat?" Well, that also doesn't seem to be an issue.

But you have to remember, the earlier you take the medication, the better off you are, the less morbidity, the less mortality, the less interference with quality of work and productivity. You don't want to wait until your throat is really super swollen, and you don't want to wait until you're already vomiting before taking your medication. Taking the drug early is what you really need to do.

Again, I think these 2 drugs, because they both have good safety records, they both work, they are going to be, once approved, the least burden for the patient, one because of the infrequent dose and the other one because it's oral instead of injectable. It makes really sense to me to use them as one for rescue and the other one to prevent attacks from occurring.

When can clinicians expect both treatments to become available?

Garadacimab is already approved in many countries, including many in the [European Union] EU. It's not yet approved in United States. We expect it any day. [Editor's note: the interview took place before the approval.] Once it is approved, hopefully the launch would be rapid and then hopefully accessible. Sometimes in the first 6 months a drug is out, insurers don't cover it. But I think in this case, because of the efficacy and the infrequent dosing, it would probably be the preferred drug.

In the sense of sebetralstat, it's also approved in many countries but not yet in United States. They were expecting it last week. It looks like that's going to be deferred for a month. Nothing to do with the medication itself. [It] has to do with backlog in the FDA, from what I understand, at least. I think it's going to have that same problem that is the first 6 months, an insurer can deny the application for the drug, or the prescription for the drug. But again, I don't think that's going to occur, because I think it has some unique qualities that will make it actually the ideal drug for rescue.