Drug Safety Developments

Study Suggests HCV Clearance with DAAs Lowers the Risk of Liver Cancer

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Background

Hepatitis C virus (HCV) treatment drugs--such as Harvoni, Sovaldi, Viekira Pak, and Technivie--are classified as Direct Acting Antiviral Agents (DAAs).

The relationship between DAA treatment and liver cancer, or hepatocellular carcinoma (HCC), is a complex one that has been the subject of several studies in the past year.

While some studies found an increased risk of liver cancer in those who used DAAs, others found insufficient evidence for such a link, or even evidence that showed a reduced risk with DAA use.

Norah Terrault, MD, of the University of California San Francisco addresses the earlier studies on the topic in an article by Medpage Today published October 23, 2017:

Terrault said the apparent increase in HCC risk was probably seen because the physicians were treating sicker patients with the DAAs, patients who would not have been eligible for the more toxic and arduous earlier regimens.

 

New Research

The most recent study on the topic was published in Gastroenterology earlier this month, and examined new cases of liver cancer in HCV patients, rather than recurring cases.  Information on the study can be found in the following press release: "Direct‐Acting Antiviral Medications Cuts Risk of Liver Cancer by 71%."

This study was based on the largest number of patients to date.  It examined over 62,051 patients in the VA healthcare system from 1999 to 2015.  Among those patients, 21,948 received DAA treatment alone, as opposed to interferon treatment or a combination of the two types of treatment.

As indicated by the title, the researchers in the study found that there was a 71% reduction in the risk of liver cancer among patients who achieved sustained virological response (SVR).  Otherwise put, among those who are cured of HCV--by DAA treatment, or otherwise--the risk of being diagnosed with liver cancer decreases by 71%.

 

The Fine Print

George N. Ioannou, MD, MS, of the University of Washington School of Medicine, Seattle, provides an interesting caveat to this statistic:

However, patients with hepatitis C may already have developed cirrhosis or advanced fibrosis before the hepatitis C is eradicated, which may put them at risk of liver cancer even after hepatitis C is eradicated.

Furthermore, those who achieved SVR had a lower risk of liver cancer in general, regardless of the method.  This suggests that DAA treatment alone is not to be lauded for the reduced risk.

Additionally, the risk reduction percentages change among patients with cirrhosis; only a 50% risk reduction was observed in these patients.

Finally, the researchers in the study note that their findings may not be sufficient to establish a causal relationship between HCV cure and reduced risk of liver cancer.

Another point of interest is that Dr. Ioannou disclosed a relationship with Janssen, the manufacturer of Olysio, a DAA.  Dr. Terrault, though not directly involved in the study, also disclosed relationships with Abbvie, Gilead, Bristol-Myers Squibb, and Merk, all of whom manufacturer DAAs.

Please know that our law firm is NOT currently handling cases involving liver cancer and DAA treatment.  However, we will continue to monitor the medical literature on the topic and report significant new developments.

 

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Previous articles on this topic:

• August Update: Possible Link Between Hepatitis C Drugs & Liver Cancer
• July 2017 Update: Any Link Between Hepatitis C Drugs and Liver Cancer?
• No Link Seen Between Sovaldi Or Harvoni And Liver Cancer Recurrence
• Can Hepatitis C Drugs Harvoni Or Sovaldi Cause Return Of Liver Cancer?
• Is The Risk Of Liver Cancer Increased From Use Of Harvoni Or Sovaldi?

August Update: Possible Link Between Hepatitis C Drugs & Liver Cancer

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

In the past several years, there has been much controversy surrounding the possible link between a class of Hepatitis C drugs known as direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC), or liver cancer.  The DAA drugs include Harvoni, Sovaldi, Viekira Pak, Technivie, Olysio, Daklinza, Epclusa, and Zepatier.

In July, I wrote an article on a study that was posted in the July 2017 edition of Gastroenterology that weighed in on this controversy.  This study provided additional evidence that DAA treatment does not entail a higher risk of liver cancer.

Although the articles that have been published on the potential link between DAAs and liver cancer tend to conflict with one another concerning whether a definite causal relationship occurs between the two, there are some points of agreement.  A recent Medscape article discusses these commonalities in detail, and is the source for the information below.

Firstly, advanced liver disease carries the strongest risk for liver cancer development.  One study found that in addition to advanced liver disease, treatment failure was also associated with HCC.  

Another study pointed out that patients treated with DAAs are more likely than untreated HCV patients to have conditions that independently increase their risk of liver cancer.  Rather than the DAAs themselves, these conditions--such as older age, cirrhosis, and portal hypertension--may be to blame if a patient treated with DAAs experiences an occurrence or recurrence of HCC.  

Moreover, additional research suggests that patients who develop HCC after DAA therapy may have had unidentified tumors present before DAA treatment ever occurred.  However, some research proposed a theory that DAAs may reduce the immune system's ability to target certain tumors, which may be responsible for their formation in patients with cirrhosis.

Secondly, many studies show a decreased rate of newly-occurring liver cancer in patients with HCV cirrhosis after sustained virologic response (SVR) due to DAA treatment.  See my previous article for a list of some of these studies. 

Thirdly, patients with active liver cancer show lower rates of SVR, which means that they are less likely to have the Hepatitis C virus absent from their blood for more than 12 weeks.

Until a definitive causal link between DAAs and liver cancer is--or is not--drawn, we will continue to monitor the medical literature for more information, and report on significant developments.

 

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July 2017 Update: Any Link Between Hepatitis C Drugs and Liver Cancer?

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

A recent study from the July 2017 edition of Gastroenterology sought to investigate the relationship between Direct Acting Antiviral Agents (DAA) -- such as Harvoni, Sovaldi, Viekira Pak, and Technivie -- and liver cancer, or hepatocellular carcinoma (HCC).

Previously, the medical literature on this subject was relatively sparse, as well as conflicting.

The following studies claim that DAA treatment is associated with an elevated risk of liver cancer recurrence:

• April 2016: Journal of Hepatology
• June 2016: Journal of Hepatology
• April 2017: Practice Update

However, the studies listed below either found insufficient evidence to declare a link between DAA and liver cancer recurrence, or evidence to the contrary:

• May 2016: Journal of Hepatology
• November 2016: Practice Update
• April 2017: Health Canada

The most recent study, titled "Risk of Hepatocellular Cancer in HCV Patients Treated with Direct Acting Antiviral Agents," tips the scale, so to speak, by providing further evidence that DAA treatment does not entail a higher risk of liver cancer.

The conclusions of this study are as follows:

Among patients treated with DAA, [sustained virologic response (SVR)] was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute HCC risk remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.

Otherwise put, these researchers found that DAA treatment does not promote liver cancer.  In fact, they observed that DAA treatment is associated with a reduction in the risk of liver cancer.  However, those with cirrhosis who have undergone DAA treatment may still be at an elevated risk.

 

A quote from the researchers who conducted this study -- excerpted from a recent Healio article -- provides the following information:

“Our data highlight the potential consequences of delaying treatment — either by lack of access or by patient/provider choice — on subsequent risk of HCC, and support treatment of all patients with HCV prior to their progression to advanced fibrosis and cirrhosis. Delaying treatment until patients progress to cirrhosis might be associated with substantial downstream costs incurred as part of life long HCC surveillance and/or management of HCC,” the researchers concluded. “We did not find any evidence to suggest that DAAs promote HCC either during or after treatment.”

Though at this juncture it seems as though DAA treatment does not lead to an increased risk of liver cancer recurrence, we will continue to monitor the medical literature for more information on this debate.

 

 

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Safety of Hepatitis C Treatment Drugs Called Into Question

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A

 

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UPDATE: 

On February 14, 2017, the FDA released a Black Box warning for these drugs with the following text:

Hepatitis B virus (HBV) reactivation has been reported, in some cases resulting in fulminant hepatitis, hepatic failure, and death. 

(2/16/17).

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Recently, the safety of the newer hepatitis C treatment drugs -- such as Solvadi and Harvoni -- is being called into question.  These drugs are known as direct-acting antiviral (DAA) drugs, and come with a steep cost of approximately $1,000 per pill.  

Here is a list of DAAs currently available in the US:

• Sovaldi (sofosbuvir) — Gilead Sciences
• Harvoni (ledipasvir and sofosbuvir) — Gilead Sciences
• Viekira Pak (dasabuvir and ombitasvir and paritaprevir and ritonavir) — Abbvie
• Viekira Pak XR (dasabuvir and ombitasvir and paritaprevir and ritonavir) — Abbvie
• Epclusa (sofosbuvir and velpatasvir) — Gilead Sciences
• Daklinza (daclatasvir) — Bristol-Myers Squibb
• Olysio (simeprevir) — Janssen
• Technivie (ombitasvir and paritaprevir and ritonavir) — Abbvie
• Zepatier (elbasvir and grazoprevir) — Merck Sharp Dohme

A report issued by the Institute for Safe Medication Practices (ISMP) provided information on the possibility of liver injury, liver failure, and reactivation of hepatitis B in patients who were treated with DAAs such as Solvadi and Harvoni.  This report is based on the adverse drug event reports submitted to the FDA, also known as MedWatch reports.  

Here is an excerpt from the ISMP QuarterWatch report, which provides details on the number of adverse drug effects that have been reported to the FDA:

The FDA report described 24 cases of hepatitis B reactivation, including 3 cases of acute liver failure, a catastrophic drug adverse event involving damage to the liver so severe that continued survival is threatened. Searching beyond the FDA’s cited cases to review the most recent 12 months’ FAERS data, we identified 524 reported cases of liver failure associated with the drugs, and another 1,058 reports of severe liver injury. In a further 761 cases the adverse event was antiviral failure against the targeted virus. Our data show the need for further investigation into the negative consequences of these expensive and important new drugs.

This WebMD article provides some additional statistics:

The study said about 250,000 people worldwide took the newer drugs in 2015. Among patients treated with the drugs during the year ending June 30, 2016, 524 suffered liver failure, and 165 of those patients died...The study also said the drugs appeared ineffective in 761 patients.

Of note, approximately 90% of the 524 reports linking liver failure to DAAs were submitted to the FDA by health professionals.  While these hepatitis C drugs are still being prescribed at the same rate they have previously been, the FDA findings are staggering, and should be cause for alarm.

Thomas J. Moore, senior scientist for drug safety and policy at ISMP is quoted as saying the following in a recent Healio article:

This is an example of the price we pay for faster drug approval with reduced clinical testing...Don’t we really want to know more than this about a new drug treatment on which we spent more than $10-20 billion in 2015 alone? We spent more than twice as much on these direct-acting antivirals for about 250,000 patients as the NIH did on all research into all infectious diseases.

The FDA identified the first new major safety problem linked to these nine new DAAs in their Drug Safety Communication from October of 2016.  They found that these drugs were linked to the reactivation of hepatitis B, with severe health consequences such as liver transplant and death.  As a result, they expressed their intention to include a "black-box warning," the most prominent warning, in the near future.

However, as of today, January 27, 2016, the current drug label for Harvoni still does not include this warning.

We will continue to monitor the medical literature for additional information on the link between these hepatitis C drugs and their harmful side effects.  We will also be on the lookout for the new drug labels with the "black-box" warning of possible hepatitis B recurrence.

In the meantime, please feel free to complete our Free Case Evaluation if you have experienced liver injury, liver failure, or hepatitis B recurrence after using one of the nine newer hepatitis C drugs.

 

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