HIV Noninjectable Long-Acting Therapies in Development
JUN 14, 2019 | PANELISTS:JOSEPH ERON, MD; PAUL SAX, MD; W. DAVID HARDY, MD; ERIC S. DAAR, MD; IAN FRANK, MD
Joseph Eron, MD: What are the long-acting options? I mean, we have this injectable. What else might we get, do you think?
Eric S. Daar, MD: There is 1 other drug that is long-acting but not for this population, and that’s ibalizumab. We’re going to talk about the newest, I guess, FDA-approved drug.
Joseph Eron, MD: Right, so ibalizumab, how are we going to use that, Eric?
Eric S. Daar, MD: It’s really for treatment-experienced patients, but it is administered every 2 weeks. But it is probably the beginning of something new when we start thinking about the possibility of monoclonal antibodies as a therapeutic and modifying those monoclonal antibodies, so the half-life isn’t allowing for every 2-week dosing but every 4-, 8-, or 12-week dosing. And certainly there’s a lot of work going in that area, although I would argue it’s still very, very early.
W. David Hardy, MD: I think it’s important to point out, though, ibalizumab is even more medically oriented, and it has to be intravenously infused. Which does mean it’s going to have to be in a medical situation, or at least a home-nursing situation, where it can be actually set up to do it, which is more complex. And there’s no reason it couldn’t be used in HIV treatment-naїve people, as long as it was accompanied by something else that also worked well.
Eric S. Daar, MD: Yeah, but every 2 weeks isn’t going to be a game changer probably, especially as you say, it’s so complicated.
Paul Sax, MD: And expensive.
W. David Hardy, MD: And expensive.
Eric S. Daar, MD: Maybe the price would come down if people used it.
Joseph Eron, MD: And fostemsavir? Paul, can you say anything about fostemsavir?
Paul Sax, MD: Yeah. It’s an attachment inhibitor, orally available twice daily.
Joseph Eron, MD: Twice daily, sure.
Paul Sax, MD: It is being looked at in the same population, a very small population of patients with multidrug-resistant HIV who really don’t have other options. We’ll see.
Joseph Eron, MD: Yeah, it will be used by experts, right?
Paul Sax, MD: Exactly.
Joseph Eron, MD: It will really be for people who have multidrug resistance.
Paul Sax, MD: I think 1 thing that I keep having to clarify to people who don’t know this field as well as we do is that there are a lot of people with multidrug-resistant HIV out there. But most of them are suppressed. It’s only for people who are failing, so it’s a very tiny patient population.
Eric S. Daar, MD: And have been suppressed for a long time.
W. David Hardy, MD: Yeah.
Paul Sax, MD: Yeah.
Joseph Eron, MD: It’s good. And then there are a couple of exciting molecules that are incredibly potent—there’s the MK-8591, or EFdA [4'-ethynl-2-fluoro-2'-deoxyadenosine], and then there’s a capsid inhibitor—that are incredibly potent, like picogram levels.
Paul Sax, MD: Amazing.
Joseph Eron, MD: How might they be used?
W. David Hardy, MD: Well, it’s curious, MK-8591 could be used on a once-a-week basis, but currently it’s being studied on a daily basis with a very small dosage. And then there’s recently, with data presented last summer in which it actually was put into a slow-release sort of implant. The great news of it is that has a lot of great characteristics, a slightly different mechanism of action, which makes it more resistant to resistance as an NRTTI [nucleoside reverse transcriptase translocation inhibitor]. And the fact that it is long lasting. But it has to be paired with something else that has similar sort of scheduling to actually make it work.
Joseph Eron, MD: And maybe this capsid inhibitor, right, makes a lot of similar properties.
Paul Sax, MD: That kind of potency and potential for less frequent dosing.
Joseph Eron, MD: And kind of a very long half-life.
Paul Sax, MD: Definitely.
Joseph Eron, MD: At least in animal models.
Eric S. Daar, MD: Very early stages.
Paul Sax, MD: Very early, yeah.
Joseph Eron, MD: Yeah.
Ian Frank, MD: And maybe more of a role in prevention than in therapy.
Paul Sax, MD: Which one?
Joseph Eron, MD: Either one.
Ian Frank, MD: Either one.
W. David Hardy, MD: As a single drug.
Ian Frank, MD: As a single drug but long acting and well tolerated.
Joseph Eron, MD: If there were partners for MK-8591—which is a nucleoside, but as David pointed out, it kind of works in 2 steps in the reverse transcriptase process. If you could get 1 pill once a week, I saw that from South Carolina in Duke.
Paul Sax, MD: Yeah, exactly.
Joseph Eron, MD: Heaven forbid.
Paul Sax, MD: Right near you but not you.
Joseph Eron, MD: Not us, yeah.
Ian Frank, MD: You does not equal you.
Joseph Eron, MD: But yeah, I think once weekly would have some attraction. We’ll see.
Paul Sax, MD: We’ll see.
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