What's in a name? For Gilead Sciences (NASDAQ:GILD), a few billion dollars.
Tenofovir alafenamide and tenofovir disoproxil fumarate may sound similar enough (and also a mouthful), but tenofovir alafenamide, commonly referred to as TAF, is worth a heck of a lot more to Gilead Sciences than tenofovir disoproxil fumarate, which goes by the brand name Viread.
Gilead Sciences' exclusivity on Viread, which is a component of its HIV cocktails Atripla, Stribild, Complera, and Truvada, expires in 2018. If Gilead Sciences can swap TAF for Viread in those cocktails and switch patients onto the new regimen, it can extend the time without generic competition. Atripla, Stribild, Complera, Truvada, and Viread are on pace to sell over $9.4 billion combined this year.
Step 1: Prove they're equivalent
Earlier this week, Gilead Sciences announced that two phase 3 trials met their primary endpoints of lowering the viral load to less than 50 copies per mL of blood. In one trial, 93.1% of patients taking the TAF containing regimen that's equivalent to Stribild reached their viral load goal compared to 92.4% for patients taking Stribild. In the other trial, the TAF version of Stribild did slightly better, with 91.6% of patients reaching their goal compared to 88.5% for Stribild.
The efficacy is close enough to call TAF non-inferior to Viread, which is all Gilead Sciences was really trying to prove for the efficacy component of the trial.
Step 2: Prove TAF is safer
The jury is still out on this one, but it's looking good for Gilead Sciences.
TAF looks better than Viread in a couple of laboratory tests measuring kidney (renal) function and bone mineral density. Viread's label warns that side effects "can include acute renal failure," and there's the potential for "decreases in bone mineral density."
On the downside, TAF increases the levels of LDL cholesterol -- that's the bad kind -- compared to Viread. While the difference was statistically significant, LDL cholesterol levels only went up 15 mg/dL in one study and 11 mg/dL in another study; depending on where the patients started, those increases might not be enough to push the LDL levels high enough to justify taking a cholesterol-lowering drug. TAF also increases levels of good HDL cholesterol, so doctors may not be so worried about the increase in LDL cholesterol.
Will patients switch?
Clearly there's no reason for patients to use TAF over Viread -- especially after generic versions of Viread are available -- unless TAF is reliably safer.
The data from these two trials comes after 48 weeks of treatment, but both trials are still ongoing. The safety aspects of the 96-week data should give us a longer-term indication of how much safer TAF is compared to Viread.
Gilead Sciences also has two more phase 3 trials left to read out. One trial is testing the switching of patients from Stribild, Atripla, and Truvada to the equivalent TAF-containing regimens. Look for efficacy to be similar with better renal function and bone mineral density for the TAF-containing regimens.
The other study is testing HIV patients with mild to moderate renal impairment. Starting with patients who already have a problem with their kidneys should make TAF's safety more apparent. While Gilead Sciences would like all patients to use TAF, not just those with renal impairment, the biotech can use the trial results to show doctors what might happen if Viread induces renal impairment and then makes things worse.