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In-depth Merck release on new Hep C drug skirts some of the basics

Merck Receives FDA Approval of ZEPATIER™ (elbasvir and grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults Following Priority Review

Our Review Summary

Hepatitis CMerck’s PR release fills us in on its freshly FDA-approved drug — Zepatier (elbasvir and grazoprevir) — to treat two different forms of hepatitis C and claims to “cure” upwards of 94% of infections based on 12- and 16-week trials. The combination pill is taken once a day throughout treatment. The release seems targeted primarily to healthcare professionals, rather than consumers, so it’s chock-full of jargon and statistics. While the release indicates the risks, benefits and costs, we saw some weaknesses in the presentation of the evidence. For example, the news release did not provide the outcomes for the placebo group, even though the studies compared the drugs with placebo. Nor did it explain that the outcome assessed — sustained virologic response — is a short-term proxy for the longer-term results that patients really care about, such as rates of liver failure and cancer.

Speaking of costs, what this release doesn’t cover (although who would expect a for-profit drug company to do so?) is the insane cost of specialty drugs, the rising demand for them, and their increasing burden on the U.S. healthcare system. HealthNewsReview.org contributor Trudy Lieberman expands on this issue in a recent blog post, which happens to focus on another (very expensive) hepatitis C drug. 

 

Why This Matters

Hepatitis C is caused by a virus that attacks the liver — an organ you can’t live without because it breaks down toxins, fights infections, helps regulate metabolism, and aids digestion. Infections can be passed down in a variety of ways, including from mother to child (during pregnancy), use of unsanitary needles (e.g. drugs or tattoos), or having sex with someone who’s infected.

Severe infections can lead to liver transplants, and cure rates with drugs in the past decade were less than 50%. Treatment has evolved rapidly as new drugs hit the market each year. Now drug sponsors are claiming that 80% to more than 90% of chronic infections can be essentially eliminated with drugs, but they do not come cheap. Harvoni, made by Gilead, costs $94,500 per 12-week course of treatment — $1,125 per pill. Gilead’s other hepatitis C drug Sovaldi costs $84,000 per course. And now Zepatier, made by Merck and now FDA-approved, costs $54,600 — what the Financial Times called the latest volley in a hepatitis C drug price war.

Unfortunately, the need for such expensive drugs is on the rise, and with it is an increasing burden on the healthcare system. About 3.5 million people in the US live with chronic hepatitis C. And according to the CDC’s latest estimates, the number of new US cases is growing: There were about 16,500 new cases in 2011, 24,700 new cases in 2012, and 29,700 new cases in 2013 — and more than three quarters of these cases lead to a chronic infection. The effect of these drugs on outcomes of reducing effects of Hep C virus on the liver, longevity or cancer rates has never been proven or quantified.  Before we can talk about the effect of the price of the drug, we need to quantify the effect (NNTB) of the drug for patients with symptomatic or asymptomatic Hep C.

Criteria

Does the news release adequately discuss the costs of the intervention?

Satisfactory

We’re told a 12-week regimen costs $54,600. However, we’re not clued in as to how much a 16-week treatment costs and that’s important since some of the trials lasted 16 weeks. Generally, according to the NIH, treatments take anywhere from 24 to 48 weeks. It’s unclear if this is true of Zepatier, although the results seem to indicate one round of treatment is all you need.

There’s also a notable addition in this release in regard to cost: Financial assistance that brings the cost down to “as little as $5 for each prescription” for private insurance plans that aren’t generous when it comes to drugs. As the recent HealthNewsReview.org post by Lieberman might suggest, this is part of a growing trend to conceal the true cost of expensive drugs to the consumer, forcing those with more substantial insurance plans to foot the bill. “Do we want the health system to work for a few or for everyone?” Lieberman wrote. “That should guide our reporting when the next news release touting the newest specialty drug shows up.” 

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Satisfactory

After 12 to 16 weeks of treatment, Merck claims its drug can cure two types of hepatitis C in 94% of people. This includes people who had cirrhosis, HIV or kidney impairment. However, it should have been explained that the response or “cure” refers only to the reduction of viral load, which does not address long-term effects or adverse effects of the drug. The benefits are given in absolute terms, but viral loads are not reported and the response or viral loads in the placebo group are not reported at all in the release. This would be a critical element to be adequately reported in describing the results of studies on the efficacy of a particular drug. Finally, since some of the patients already had cirrhosis, there is no way the drug can prevent this outcome, and the needed study outcome should be reduction in the rate of liver or other GI cancers.

Does the news release adequately explain/quantify the harms of the intervention?

Satisfactory

The discussion on harms includes a long list of drugs to avoid mixing with Zepatier as well as common side effects and adverse reactions including headaches, fatigue, nausea, and anemia in about 5% of people who took the drug. Although we wouldn’t expect harms from placebo to be severe, we expected to see at least a mention of them since the drug was compared against placebo. And, since the minor harms were listed so extensively, we would have liked to see a mention of the risks for more rare but serious side effects due to the drug. In its news release on the approval, the FDA writes, “Zepatier carries a warning alerting patients and health care providers that elevations of liver enzymes to greater than five times the upper limit of normal occurred in approximately 1 percent of clinical trial participants, generally at or after treatment week eight.”

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

Drugs must pass high bars to achieve FDA approval, and here we’re given the detailed results in five randomized, double-blind clinical trials for one form of hepatitis C (GT1 HCV) and one trial for another — GT4 HCV. Each of the trials used a few different populations with different pre-existing conditions. Despite the exhaustive accounting of study results, we’ll ding the release here for not acknowledging that the studies were all designed to find the “disease oriented” and not “patient oriented” outcomes. This means that the trial looked at the reduction in viral load, not the prevention of specific conditions like cirrhosis, an outcome that is supposed to be prevented by the use of these drugs. Patients care most about conditions that affect them and not how many virus particles are in their blood, so this was an important omission.

Does the news release commit disease-mongering?

Satisfactory

There are no harrowing, overly dramatic details here.

Does the news release identify funding sources & disclose conflicts of interest?

Satisfactory

Merck is clearly labeled as the sponsor of the release.

Does the news release compare the new approach with existing alternatives?

Satisfactory

In the clinical trials section, some alternative treatments are named, including “IFN or PegIFN ± RBV” and “boceprevir, simeprevir, or telaprevir in combination with PegIFN + RBV.”  We’ll award a Satisfactory on that basis, although the trials mentioned are all compared against placebo and not these drugs. It would have helped to know what those treatments are, and their effectiveness. We will note, however, that highly successful curative hepatitis C treatments are very new — basically, within the past few years. The alternatives prior to that were liver transplants, which can cost $300,000, and viral interferon treatments, which were less than 50% effective.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

Merck’s release states the drug will start shipping to wholesalers within 7 days of Jan. 28, 2016.

Does the news release establish the true novelty of the approach?

Not Satisfactory

This is the second one-pill, once-a-day option for hepatitis C. We don’t think the release demonstrates novelty. “Multiple therapeutic tools” to treat hepatitis C are mentioned in a quote by the executive director of the Hepatitis Education Project, but we’re not clued in to what those are or where Zepatier fits in. Alternative drugs have similar, albeit slightly lower, cure rates in the high-80% to low-90% range.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Not Satisfactory

We see the word “cure” four times in the release. The release defines its use of the term cure early on in the release as “Sustained virologic response is defined as HCV RNA levels measuring less than the lower limit of quantification at 12 weeks after the cessation of treatment (SVR12), indicating that a patient’s HCV infection has been cured.”  We disagree because there’s no indication that these “sustained” responses are prolonged for a long period after the drug is discontinued.

Total Score: 7 of 10 Satisfactory

Comments (2)

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Debbie lawler

February 11, 2016 at 6:12 am

I’ve had the worst so called side effects, my liver is so enlarged I’ve had to go to the ER, it’s irresponsible to not inform the public about lack of experience on people with esld & the possibility of causing more harm to MY liver.

Reply

Thomas Burgoon, MD

February 16, 2016 at 4:13 pm

Thank you for this review. My questions as a physician include ‘what happens after 12 weeks?’ It is a bit misleading to the public to keep advertising about a ‘cure’ when actually they are referring to a sustained virologic response of only 12 weeks. Also, your points about important clinical results such as evidence regarding liver transplant or progression to cirrhosis is very important. Furthermore, no data on how the placebo groups compared here. Without the above information, it is hard as a physician to recommend this therapy yet.

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