Hepatitis is a fancy word for liver inflammation. Sounds just somewhat serious, right?

Wrong, infections that cause Hepatitis can be a very grim business. In fact, they are responsible for one of the world’s largest healthcare burdens.

Hepatitis can be caused by different viral infections that are designated by the astonishingly creative nomenclature of A, B, C, D, and E. Hepatitis C (HCV) is what we will focus on today. ~200 million people carry this virus around inside them, including 3-4 million Americans. Ten times as many people are infected with HCV than HIV.  It is the most common blood-borne viral infection in the world and is responsible for substantial amounts of morbidity and death.

HCV is known as the “silent killer” because ~75% of those infected are unaware they carry the virus. Furthermore, some infected individuals may only show obvious symptoms many years after they are infected. By that time, however, they may already be suffering from serious liver damage.

Vaccine development has been successful for Hepatitis A and B, but not for HCV because the virus undergoes multiple mutations and therefore does not present a common target for vaccine developers. Given that there is no vaccine, the only available treatment for HCV infection is anti-viral drugs.

For the last decades, people suffering from HCV infection have not had great choices. The standard of care, interferon and ribavirin, had low success rates and were accompanied by serious/debilitating side effects. These treatments only worked about half the time and made people who were already sick even sicker from potent side effects.

This is a key point, as both the fear and reality of side effects from HCV drugs are a main cause of 1) not even starting treatment in the first place, and 2) premature treatment cessation.

When treatment is terminated early stronger variants of the virus can replicate - making any subsequent treatment attempt less likely to succeed and significantly increasing financial costs. Accordingly, the side effect profile of HCV drugs is a particularly big deal as strict patient adherence to HCV treatment regimens is vital.

The recent introduction of new HCV drugs, known as “direct-acting antivirals,” is a radical, and welcome, change from the past “standard of care” mentioned above.

Or is it?

In with the New Drugs: Looking like Good News on Efficacy

For the type of HCV infection common in the US and Europe, “cure” rates have appeared to skyrocket from ~50% to 90+%, seemingly overnight. While the efficacy of these new drugs seems to be superior to past regimens, questions still remain about their true effectiveness and also their side effect profiles – mainly because their history of use is so short.

So far, Gilead’s Sovaldi (sofosbuvir) looks poised to achieve an almost total market domination based on its excellent efficacy and, at least to-date, very favorable side effect profile.

Not all is rosy, however. Both Sovaldi’s assumed efficacy profile and, especially, its’ price tag are creating a firestorm of opposition.

The National Association of Medicaid Directors, for example, recently stated: “Based on its rigorous review of the ten published sofosbuvir studies, the Center found that each was of “poor” methodologic quality, noting risks of bias and lacking comparison to current standards of hepatitis C treatment. None of the studies were designed to answer the question of whether these drugs work better than current treatments and for the people most likely to have them prescribed. The report also questions the soundness of treatment guidelines published by the American Society for the Study of Liver Disease, noting the guideline methodology did not rigorously examine the aforementioned studies to assess their weaknesses.”

Additionally, a recent cost estimate suggested that an additional 20 billion dollars would be needed just to treat half of those infected with HCV in California alone. 20. Billion.

Accordingly, provider groups are scrambling to contain this impending potential cost nightmare. In order to stem the surge of patients clamoring for Sovaldi they are implementing various authorization guidelines including prescription only by specialist physicians, proof of interferon intolerance, the need for liver biopsies, requirements for previous treatment failure, viral load tests early in treatment to assess patient adherence, etc.

In short, controversy swirls around just how efficacious these new drugs are, and whether they present an economically sound treatment choice. Patients, however, have heard the efficacy success stories and now assume Sovaldi is a miracle drug. They want it, now.


Related Read: Hepatitis C Payer Scorecard: According to Peers, Express Scripts DID Make the Wrong Decision

The New Drugs are Safe, Right? Not So Fast.

Knowledge about side effects, especially from newly introduced drugs like Sovaldi, is very limited. A drug’s true side effect profile is never fully elucidated until after, sometimes years after, FDA-approval.

Why? Well, the main reason is that pre-approval clinical trial processes cannot provide a thorough safety profile because those testing regimens suffer from many limitations like enrolling only relatively homogenous groups of patients, short drug exposure times, ever-increasing exclusion criteria, lack of gender-specific analyses, inadequate testing of the elderly and different races, etc., etc.


Related Read: Post Approval Adverse Events... What's the Real World Impact? [INFOGRAPHIC]


All of these restrictions can result in very different reactions, especially with regard to side effects, in clinical trial subjects compared to the real-world consumer populations that end up taking them.

In short, when a drug is approved most patients assume it has already been “proven” to be safe. This is absolutely not accurate. For more detail, please see a White Paper we recently produced, “Post FDA-approval drug safety data: why they are vital and how they can be made accessible, actionable, and predictable.”

Sovaldi, so far, appears quite safe, especially when compared to other HCV drugs. However, we’ve only be able to analyze ~400 side effect case reports to date because the drug is so new.

Time, and more side effect reports from real-world patient populations, will tell.

AdverseEvents, through a combination of our daily adverse event diligence and Freedom of Information Act services, will keep our clients as up to date as possible regarding side effects associated with HCV drugs.

That is what we do, and we love it.

For more information please see our recent Special Report: The Comparative Safety of Hepatitis C Medications.”

Drug Safety Monitor Report - Viekira Pak Hepatitis C

Keith Hoffman

Keith Hoffman, PhD

Vice President, Scientific Affairs

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Topics: Drug Safety, Drug / Indication Information

Dr. Keith Hoffman

Written by Dr. Keith Hoffman