Some Things Considered

I am an outlier,

But I am happy.

Treatment to cure is every person with Hep C's goal. When things get closer to the end it can consume us to find the keys to the locked exit doors. Even in my early 20s I gave up hope when Int/Riba failed, I grasped at straws and took the treatment again with a higher dosage.

That grasping, failing, created my first RAV, I had a q80k polymorphism. Failing a treatment is not simply continuing to have HCV but it also bears the risk of creating mutations, RAVs. 

So after failing Int/Rib/Incivek, Sovaldi/Olysio, Harvoni... I now have three mutations, RAVs.

I am an outlier, but one or two RAVs is common among experienced patients.

Zepatier, the drug i've been waiting for had a contradiction I was worried about. While previously I was unsure my Child-Pugh score; I confirmed that it is only A. Which means it shouldn't be as hard to get access to the meds.
Daklinza/Sovaldi/Olysio/Riba is another contender.

(to make things even more complicated, the existence of RAVs from a previous treatment does not indicate that the treatment will or will not necessarily fail)

Well....fuck.  There isn't enough longitudinal data for my situation on these meds to make the best decision. Why? Because breakthrough medications often lack the studies their non-breakthrough partners have at date of FDA approval.  Breakthrough therapies are not about the results, they're about maximizing the amount of time the patent is most profitable.

Zepatier will undoubtedly change the conversation about Hep C meds due to its lower price point and high efficacy in smaller groups as well as across Genotype 1 and 4.  I fear that this low price point will drive a "consumer's" choice in treatment. 

(Insurance agencies, Healthcare groups and Pharma companies make the real choice between medications before you even see em... which means 1/3 of the people deciding  give a shit about the patient. Fucking Trident has more support from leading dentists.) 

There are many combinations of Hep C meds for many different cases, each one with different efficacies. (Sovaldi ranges from 84-96% depending on subtype.)

The best drug/therapy to treat should be set by relative efficacy, not by price.

That being said, my condition is stable, I don't seem to be getting worse, nor am I getting better. If I keep up the healthy changes I've been making I may be able to stay where I am for a few years yet.

The key now is choosing the best treatment, which means waiting for more data. Thankfully the EASL (aka the International Liver Conference) is coming up next month, so we should have more information in the coming months.

In the meantime later this month I'll be making a trip to Portland and Seattle. Making stops in San Francisco, and Sacramento.

If you're along the route, ping me! 

Zepatier Part Ugh

I have spent the better part of this past month re-writing this post, and on March 11, i will find out much more.

Because I legitimately don't know how to properly convey my despair and disappointment and fear at what will soon unfold.

I had been eagerly awaiting the release of Zepatier,  the announcement last month was terribly exciting.

Zepatier is a Hep C drug that deals with NS5A resistance,has a very high success rate, and is almost half the price of the leading treatments Harvoni and Sovaldi.

It's amazing, and it has shown to work very well in other harder to treat cases.


The drug has one small hitch.

Well, i think it kinda sucks like... a lot.

The FDA/Merck released a contraindication for the drug for use with patients who with child pugh score B or C

"ZEPATIER is contraindicated in patients with moderate or severe hepaticimpairment (ChildPugh·B or C) due to the expected significantly increased grazoprevir plasmaconcentration and the increased risk of alanine aminotransferase (ALT)elevations" - 

The contraindication does have a rationale beneath it.

In 1% of cases ALT levels raised 5X within in the first 8 weeks, Clearly, an indicative factor of a problem.

Unless it isn't.

Which it isn't.

Most instances self corrected soon after:

" During clinical trials with ZEPATIER with or without ribavirin, regardless of treatment duration, 1% (12/1599) of subjects experienced elevations of ALT from normal levels to greater than 5 times the ULN, generally at or after treatment week 8 (mean onset time 10 weeks, range 6-12 weeks). These late ALT elevations were typically asymptomatic. Most late ALT elevations resolved with ongoing therapy with ZEPATIER or after completion of therapy [see Warnings and Precautions (5.1)]. The frequency of late ALT elevations was higher in subjects with higher grazoprevir plasma concentrations [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. The incidence of late ALT elevations was not affected by treatment duration. Cirrhosis was not a risk factor for late ALT elevations."

In fact the contraindication seems odd considering the big new DAAs carried no such contraindication:
 Sovaldi 
Harvoni 
Daklinza 

Olysio 

"Initial analysis of Zepatier’s label showed comparatively fewer AE(Adverse Effects)s (29 vs 41 for Sovaldi). Liver cirrhosis, the only ImportantMedical Event (IME) listed on the label, is largely associated with HCV and notwith the drug. "

So... Now it's time to figure out how the hell I get this drug, because I suspect this will be my last treatment. success or failure.
Further research should show it's true efficacy, which i feel will reflect poorly on Zepatier if the drug is prioritized because of its price-point rather than it's efficacy.

Hope is not a four letter word

Merck.

We've been seeing DAAs like Sovaldi come out lots of labs, but we're about to witness the rest of the big companies throw their hat into the ring. Gilead's use of the Warehouse of Hep C (HCV) patients has led to historic profits for Gilead. Johnson and Johnson's Olysio tapped into the market, and Bristol Myers Squibb's new Daklinza (daclatasvir) are filling the gaps Gilead's Sovaldi left.

And soon Merck is about to throw down one of the most virally specific DAAs around. The new combination treatment will be able to cure even cases previously failed due to RAVs (mutations).

Why am i stoked?
Because it may be my sixth treatment.
So what makes it different?

Well first off two/three phases have been done with higher efficacy than Harvoni.
C-Edge and C-Salvage.
C-Edge is similar to most DAA studies, it's efficacy is unsurprisingly high.
C-Salvage as the name implies is specific not only to people who failed interfereon/ribavirin, but also failed a DAA like Sovaldi/Harvoni/V-Pak. It's going after people with NS3 and NS5A variants like myself.

The C-Salvage study has the best results i have seen for someone in my situation.

Previous treatments I've been on had an 84-86% success rate when it came down to my genotype, and cirrhosis. Usually being even lower for decompensated liver patients, however it still positively impacts MELD, so it's not all a waste.

The C-Salvage boasts an unbelievably high success rate: 96.2%

The new drugs names: grazoprevir and elbasvir.

So damn catchy, aren't they?

Annnd it's slotted to be FDA approved during the early first quarter of 2016.
Annnd the new grazoprevir and elbasvir treatments could be as low as 16 weeks instead of 24.

Troubles: The study doesn't specifically mention which variations, as those may/may not have an impact on success. So in this aspect it's kinda a crapshoot, because until later this year we won't have clear enough data to say that it will or will not be successful for my specific variations.

Troubles: Price, with the way Hep C meds are presently being marketed it would not be surprising to see a hundred thousand dollar price tag. Merck will also probably offer a massive discount program similar to Gilead's MySupportPath.

And this thing... keep an eye on the TPP...

The Trans Pacific Partnership. As i highlighted in a series of blog posts regarding why Medicaid is waiting until people are dying to cure them, the TPP will play a large role in how insurance agencies, Managed Care Organizations, Pharmaceutical costs(and carve outs) are going to be set over the next few years. 

With the TPP disclosure coming out soon, and congress to debate it, this will undoubtedly play a role in access to Merck's new meds, and the prices it offers consumers and insurance agencies.

C-Edge Study:
http://www.natap.org/2015/EASL/EASL_04.htm

C-Salvage Study:

http://hepcblog.amjmed.com/hep-c-treatment/c-salvage-final-24-week-follow-up-results/