The FDA’s Latest Hep C Drug Warning Makes Clear Why You Should Protect Your Beneficiaries From New Drugs’ Dangers

The latest FDA Black Box Warning about hepatitis C treatmentsscreen-shot-2016-10-05-at-5-20-06-pm demonstrates why it’s imperative that your Plan implement methods for protecting your beneficiaries against the dangers of new drugs.

After all, more than three years after the FDA approved the first of eight new hep C treatments, the FDA has just issued yet another warning about a newly discovered danger related to these drugs.

The FDA is continually approving new drugs. Last year, it approved 46 New Molecular Entities (NMEs). (1) And in the first 9 months of 2016, it approved another 17 NMEs. (2)

However, given the limited testing that new drugs undergo before approval, many newly approved drugs pose significant safety risks that only emerge several years after approval. Therefore, logically, only those who really need new drugs should take them.

In fact, two basic safety rules should control new drugs’ use:

  • If older meds are available – with known efficacy and safety records – those drugs should be used instead of a new drug, until more is known about the new drug.
  • If use of a new drug is unnecessary – either because a health problem will go away on its own, or a health problem poses no serious risk for many years – a new drug should be avoided.

The wisdom of these rules is demonstrated by the events that have occurred over time related to the new hepatitis C treatments.

A Short History of Hep C Drugs: From 2013 to the Present 

In 2013, the FDA approved two, entirely new hepatitis C treatments – Olysio and Sovaldi.

Since then, the FDA has approved six additional hep C treatments: Harvoni and Viekira Pak (in October and December 2014), Technivie and Daklinza (both in July 2015) and Zepatier and Epclusa (in January and June of 2016).

As is typical of virtually all newly-approved drugs, the new hep C treatments were all approved based on clinical trials containing less than 3,000 individuals. (3)

As is also typical of almost all newly-approved drugs, the hep C clinical trials that were submitted to the FDA did not test potential drug-to-drug interactions, or the safety of the tested drugs if users suffered from other diseases. (4)

As a result of all the above weaknesses in the FDA’s approval process, certain dangers about the hep C treatments only began to emerge several years after the treatments were approved.

In March 2015, the FDA issued its first new warning concerning patients taking Sovaldi or Harvoni. The FDA stated that individuals using these drugs could “develop a serious and life-threatening” slowing of the heart if either drug is taken at the same time as a drug called amiodarone. Adverse Event Reports reflected one individual had died from cardiac arrest and three required placement of a pacemaker to regulate heart rhythms. The Reports also showed other individuals suffered from slowing of the heart, but recovered after discontinuing either the hep C drugs or amiodarone, or both. (5)

In October 2015, the FDA issued a second warning based on accumulating Adverse Event Reports, this time stating that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in patients with underlying advanced liver disease, meaning careful monitoring of these patients is necessary. (6)

On October 4, 2016, the FDA issued a new Black Box Warning – the FDA’s most serious warning – in connection with all 8 of the new hep C treatments. Based on an accumulation of Adverse Event Reports, the FDA reported that all 8 of the new hepatitis C treatments may cause a previous hepatitis B infection to come roaring back – or an existing hepatitis B infection to get far worse – potentially resulting in serious liver problems or death.

Accordingly, the FDA is now warning that before starting treatment with any of the new hepatitis C drugs, individuals should be screened for evidence of current or prior hepatitis B infection. The FDA also stated that all hep C users should be monitored for hepatitis B flareups or reactivation, during – and after users finish – their hepatitis C treatments. (7) 

The FDA also added the following information to its new warning: “We identified 24 cases of [hepatitis B] reactivation … during the 31 months from November 22, 2013 to July 18, 2016. This number includes only cases submitted to FDA, so there are likely additional cases about which we are unaware. Of the cases reported, two patients died and one required a liver transplant.” (8)

Tellingly, the FDA also made two additional points: First, the FDA observed that certain individuals who were harmed were at the early stages of hepatitis C disease (meaning they had not needed treatment). Second, the FDA indicated that Hepatitis B reactivation “was not reported as an adverse event in the clinical trials submitted for … approvals because patients with [hepatitis B] co-infection were excluded from the trials.”(9)

Unfortunately, the FDA’s latest warning about hep C treatment dangers may not be its last warning. As more and more individuals use these drugs, other drug-to-drug and drug-to-disease interactions may emerge that are currently still unknown.

Hep C Implications 

The history of the new hepatitis C treatments reflects why all health plans should try to limit the use of new drugs to those who really need them.

After all, even though the hepatitis C drugs are miraculous drugs, they are not needed by everyone who has hepatitis C: Analyses vary, but from about 15% to about 37% of people clear the infection on their own. (10) And those who don’t are not at any risk from the disease for many years after they are initially infected. Therefore, why should any individual with an early disease state put himself at risk from the new drugs’ unknown dangers, given that the drugs might not be needed at all, or won’t be needed for many years? And why would your plan rationally foot the cost for any individual to do so?

The same is true for many, far less miraculous drugs. Notably, approximately 20% of all drugs require Black Box Warnings within the first seven years after approval, meaning those who use new drugs before Black Box Warnings are added are exposing themselves to serious risks that are unknown when they take the drugs. (11) 

What Should Your Health Plan Do?

Given new drugs’ potential dangers, every health plan should take steps to protect beneficiaries, as well as avoid squandering money on drug use that is ill-advised.

Consider “blocking” coverage for at least a year for certain new-to-market drugs, and for those drugs that are allowed, imposing strict Prior Authorizations that restrict use.

If you represent a larger plan that is spending millions of dollars annually on your prescription coverage, consider retaining an outside expert to provide periodic reviews and evaluations of all new-to-market drugs. In this way, you will obtain independent advice that is free of your PBM’s conflicts of interest (including its interest in increasing its rebates and other monies that it retains for its own account).

Implementing the above approaches will not only protect the health of your beneficiaries. It will also save your plan considerable amounts of money. New brand drugs virtually always cost more than existing drugs, especially when generics are available. And even if no therapeutically similar drugs are available that are equally as effective as the newly-approved drugs (as was the case with the new hepatitis C treatments), there is little reason to spend immense sums of money to provide drugs to people who don’t need them.

Even a quick review of drugs approved since January 2015 makes clear why the above advice is well grounded: There are several high-cost drugs where exclusion – or restricted use – makes sense given lower-cost alternatives, including for the treatment of diabetes (Tresiba and Adlyxin), high cholesterol (Repatha and Praluent), MS (Zinbryta, where the review team recommended the drug only be used where individuals have had an inadequate response to at least 2 other drugs), plaque psoriasis (Taltz), gout (Zurampic) and dry eyes (Xiidra). And there are other drugs of dubious value, especially given their cost. For example: Addyi (to treat women’s lack of sexual desire) and Kybella (to treat adults with moderate-to-severe fat below the chin).

In sum, unlike other industries – like cars and computers – when it comes to drugs “newer is not always better.” A new drug may make sense if it represents a break-through drug (like Gleevec), or there are no other alternatives and there is evidence of net benefit over risk. But in the other instances we identified at the outset, the potential risks of new drugs counsel that your plan should be avoiding – or limiting – coverage, until the new drugs’ risk profiles are understood over time.

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(1) See FDA website, Novel Drug Approvals for 2015.

(2) See FDA website, Novel Drug Approvals for 2016.

(3) See the following information provided by the FDA on each drug: (i) Sovaldi:; (ii)  Harvoni:; (iii) Viekira Pak:; (iv) Technivie:; (v) Daklinza:; (vi) Zepatier:; (vii) Epclusa:

(4) As it happens, in the clinical trials for Technivie, certain tested individuals were women using birth control pills, and there was a more frequent elevation of liver enzymes among those individuals. As a result, when Technivie was approved, the FDA required the inclusion of a warning that women using contraceptives containing ethinyl estradiol should discontinue use prior to starting Technivie.

(5) See FDA website, “Hepatitis Update – Important safety information: Harvoni and Sovaldi”.

(6) See FDA website, “Hepatitis C Treatments Viekira Pak and Technivie: Drug Safety Communication – Risk of Serious Liver Injury”.

(7) See FDA website, “FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C”. 

(8) Id. 

(9) Id. 

(10) See, e.g., a clinical trial showing the 37% figure, in the Journal of Hepatology, at: 

(11) See Karen Lasser, Paul Allen, Steffie Woolhandler, David Himmelstein, Sidney Wolfe and David Bor,  “Timing of New Black Box Warnings and Withdrawals for Prescription Medications,” JAMA 2002;287:2215-2220.