New FDA Approval - Epclusa

Drug

sofosbuvir / velpatasvir [Epclusa]

Indication

Epclusa is used for treatment of chronic hepatitis C (HCV). It can be used in patients both with and without cirrhosis. If the patient does have cirrhosis (moderate to severe), Epclusa should be given with ribavirin. 

Epclusa can be given all by its lonesome self if there is no cirrhosis or if cirrhosis is in earlier stages. 

Also, this is the first ever drug combination that can be used to treat all six major forms of HCV. 

How it Works

There are two components to Epclusa...

Sofosbuvir is an NS5B RNA-dependent polymerase inhibitor. 

Velpatasvir is an NS5A RNA-depended polymerase inhibitor.

To learn more about what the hell those things are, check out our post covering the basics of Hepatitis C. 

Notable Adverse Effects

First, let's get the NAPLEX-fodder out of the way. There are post-marketing reports of using sofosbuvir with amiodarone. Specifically, the interaction appears to be when sofosbuvir is used in combination with another direct-acting antiviral (like velpatasavir).

Long story short, you should avoid the combination. Do not use amiodarone in patients taking Epclusa if you can help it. It can cause profound slowing of the heart (bradycardia), and has required pacemaker intervention in some cases. 

If your patient is stable on amiodarone and you have no other alternatives, then it's recommended to initiate Epclusa in the inpatient setting for 48 hours. And then have close (daily) outpatient monitoring for at least 2 weeks. 

Otherwise, all things considered Epclusa is pretty well tolerated.

Headache and fatigue are the most common side effects. If the patient has decompensated cirrhosis and is using Epclusa along with ribavirin, then you also have all of the ribavirin side effects to worry about.

Just keep in mind that this was a priority review by the FDA...so more stuff will likely be uncovered as the number of patients taking Epclusa is expanded. 

The only other quick point to mention is use with acid suppressing agents. Velpatasvir requires an acidic environment to be optimally absorbed. It's recommended to avoid PPIs entirely with Epclusa. You can use an H2 antagonist instead, if you separate the dose by 12 hours (or take Epclusa at the same time as the H2 antagonist). Regular old run-of-the-mill antacids like Tums should be separated by 4 hours. 

Additionally, both components in Epclusa are P-gp substrates (and Velpatasvir is partially a 3A4 substrate), so you'll have to be on the lookout for interactions there. Particularly with strong inducers...because induction can lower the serum concentrations of Epclusa and lead to treatment failure and possibly resistance. 

Current Place in Therapy

Oh Gilead. You sure do know how to take our money. The $1000/pill sofosbuvir cash cow continues to bring home the bacon for shareholders.

But if sofosbuvir isn't a breakthrough for HCV, then I don't know what is. 

This is yet another combination of sofosbuvir that can bring > 95% Sustained Virologic Response (SVR. ie. "cure") rates in 12 weeks. Without ribavirin or interferon.

Compared to the old regime of "48 weeks of feeling like you have the flu, becoming depressed, and not being able to have children" that's pretty damn significant.

Epclusa's mark in the world is that it can be used for all 6 major genotypes of HCV. This is sort of a big deal for those patients without genotype 1.

Genotype 1 is by far the most common in the US (~75% of US HCV infections). It's also considered the most aggressive. And so most of the treatments developed have been specifically catered to Genotype 1 (because the US will actually pay $1000 per pill).

After Harvoni (another Gilead combination of sofosbuvir) was initially approved for Genotype 1, it's labeling was expanded to included Genotypes 4 - 6 as well. 

Well now we've got something that can cover Genotypes 1 - 6. We didn't have much that could help with Genotypes 2 and 3 until this. And even in the US, Genotypes 2 and 3 account for about 20ish% of HCV infections.

So while I'd hesitate calling Epclusa a breakthrough, it does streamline the treatment decision-making process. And it does provide an option for Genotype 2 and 3 where not much existed before. 

Plus money. Epclusa provides money for Gilead. To the tune of $890 per pill. Which is a solid 10% discount compared to Harvoni.