New FDA Approval: Descovy

New FDA Approval: Descovy

Drug

Emtricitabine + Tenofovir alafenamide [Descovy]

Indication

Image: www.watchfit.com Also, seriously. Why do you need an orange AND orange juice?

Image: www.watchfit.com
Also, seriously. Why do you need an orange AND orange juice?

The treatment of HIV-1 in adults and peds 12 years and older -- As part of a combination. That last part is important. Descovy alone is not adequate treatment for HIV. Much like this balanced breakfast isn't balanced without the lone hard boiled egg, sitting regally atop his porcelain tower. #ThugLife. 

You can think of it as a younger, much more expensive cousin to Truvada (emtricitabine + tenofovir disoproxyl fumarate). 

 

I feel like this drug already exists...

Well it does. Kind of. You're going to see more of these  "tenofovir 2.0" drugs coming up. You've already seen it with Odefsey (rilpivirine + emtricitabine + tenofovir alafenamide) and Genvoya (elvitegravir + cobicistat + emtricitabine + tenofovir alafenamide). 

So what's the deal?

Up until now, we've used tenofovir disoproxyl fumarate (TDF) in HIV treatment. And it's one of the more common agents used for HIV. It's an NRTI, so it makes up part of the "backbone" of HAART therapy. It's also already co-formulated into a whole bunch of combination products. Truvada, Complera, Stribild, Atripla, and Triumeq. Adding to that, TDF is used to treat Hepatitis B as well.

Anyway, suffice it to say, we have a lot of data (from a lot of patients) with TDF. And it's pretty well tolerated. But it has two common strikes against it. 

  1. It can worsen renal function -- even leading to the rare-but-serious Fanconi Syndrome (the same Fanconi Syndrome you can get by taking expired tetracyclines).
  2. It can cause bone loss 

These are legit side effects. As HIV has basically transitioned to a "chronic" disease, people live longer with it. Advances in HIV treatment have removed the 5 - 10 year death sentence that used to hang over your head when you were diagnosed. Now people can live for decades with a pretty normal life. Just look at Magic Johnson. However, as patients age, bone loss and kidney disease become bigger issues.

Anyway. Enter the selfless, humanitarian efforts of Gilead, owners of of TDF (which has a patent expiring in 2017). And they find that with a slight tweak, they get tenofovir alafenamide (TAF). It delivers the same active agent (tenofovir diphosphate) more efficiently to HIV cells. The upshot? The TAF dose is 25 mg compared to the corresponding TDF dose of 300 mg. 

How it Works

The Original NRTIs Image: Middle Earth Enterprises

The Original NRTIs
Image: Middle Earth Enterprises

Just like TDF, TAF is a Nucleotide Reverse Transcriptase Inhibitor (NRTI). So as the HIV (and HBV) virus is replicating, NRTIs insert themselves into the viral genome. They "look" just like the regular nucleotides that are supposed to be there. But they aren't functional. This is similar to how Frodo and Sam disguised themselves as orcs so they could march through Mordor undetected.

So the viral replication fails, and the HIV virus dies. Also (spoiler alert), the ring is destroyed inside Mt. Doom and Mordor collapses into itself like a dying star.   

Notable Adverse Effects

TAF is pretty similar to TDF across the board. I mean, at the end of the day it's the same drug, right? So you can think of Descovy as similar to its cousin, Truvada. Descovy has the same Black Box Warning for lactic acidosis and hepatomegaly/steatosis. If you have Hepatitis B, it might flare up if you stop taking Descovy or Truvada. 

How about that improved bone and renal bit we mentioned above?

Early data is decent. In one study where 1436 participants switched from TDF to TAF, there was an increase in bone density of 1.79% in the TAF arm (compared to a decrease of 0.28% in the TDF arm). As for renal function, there were also improvements in urine protein : creatinine ratio (a decrease of 21% for the TAF arm). They are using "different" markers for renal function because this particular study was done with Genvoya. Genvoya contains the PK enhancer cobicistat. Cobicistat can increase serum creatinine (but does not seem to actually cause kidney harm). 

Also of note was an increase in blood lipids for the TAF arm compared to TDF. Something to be mindful of.

Current Place in Therapy

It's unclear at this point. Gilead seems to be going through the entire collection of TDF combination pills and re-branding them with TAF. They're pushing for TAF to be used in the same way as TDF, but it's not there yet.

As an example, Descovy is NOT currently indicated for pre-exposure prophylaxis (PrEP), whereas Truvada is. 

These new TAF regimens offer similar (and in some cases slightly better) efficacy compared to TDF. The adverse effects and discontinuation rates are similar, but with a modest benefit for bone and renal disease to TAF. 

Also of note, TAF does not require a renal adjustment until CrCl hits 30 ml/min. The adjustment for TDF happens at 50 ml/min. 

So there's some benefit, but is it worth the (significantly) increased cost? We tend to think that post marketing data will be needed for that. Let's see how it does in a larger patient population. Gilead will certainly be pushing for Descovy and every other TAF-containing regimen to move to the front line of therapy. In fact they're already calling it the "Next Generation of HIV therapy." 

But color us "cautiously optimistic." It's hard to not see this as "Money Grab." Because Gilead has done that so effectively in the past. 

In the meantime, be on the lookout for more TAF-containing regimens. For your convenience, here's a handy list of the "cousins" that currently exist. The TAF brand is on the left, and the TDF brand is on the right:

  • Genvoya = Stribild
  • Odefsey = Complera
  • Descovy = Truvada

As a parting note...I have no idea where these new brand names are coming from. They're nearly more difficult to pronounce than the generic. 

 

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