Q&A with AbbVie's Barry Bernstein, MD: Are More FDA Warnings in the Works?

The effectiveness of the new arsenal of hepatitis C antivirals has elated physicians and patients and been a triumph—and lucrative development--for pharmaceutical companies.

The announcement on Oct. 22 that AbbVie, manufacturer of two such drug products was changing labeling to include new warnings dampened the euphoria. Post-marketing reports alerted the company and the US Food and Drug Administration (FDA) of patient deaths and severe liver damage sometimes requiring transplantation in some patients who received AbbVie’s treatments.

The company, in consultation with the FDA changed its package inserts and labeling for Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and Technivie (ombitasvir, paritaprevir, and ritonavir tablets.

Patients whose liver disease was staged at the Child Pugh B level (moderate) will now be contraindicated for the drugs. Patients classified as Child-Pugh C (severe) will remain contraindicated as they have been since approval.

In a Q&A with MD Magazine, Barry Bernstein, MD, vice president, infectious disease development at AbbVie, put the development in perspective. Bernstein, A Duke University graduate, Bernstein (photo above at left) got his infectious disease training at Ohio State University.

How do the different hepatitis C genotypes play into this safety issue?

Viekira Pak is indicated for genotype 1, which affects 70% of hepatitis C patients in the US. Technivie with ribarvirin is for patients with genotype 4, fewer than 1 % in the US, but it is very common in Egypt and the Middle East

Were your drugs helping any patients that no other drug could help?

At the time they became available there were limited options, mostly Interferon-based therapy, which has toxicity.

But in terms of genotypes, there are many drugs for genotype 1, what about genotype 4?

There are several other drugs currently available for patients with genotype 4.

[Clarifying his answer later, Bernstein said in an emai that those drugs are not available in the US, only abroad:

"TECHNIVIE was the first and only all-oral, interferon-free, direct-acting antiviral treatment approved in the U.S. for adult patients with GT4 chronic HCV infection without cirrhosis. Previously, patients with GT4 chronic HCV infection had limited approved treatment options. With the approval of TECHNIVIE used in combination with ribavirin, these patients now have available an all-oral, interferon-free treatment option that provides a high probability of a cure."]

Any idea how many patients were taking the drugs who were discontinued after the FDA warning?

I don’t have those numbers.

What can these patients do now—are other antivirals ok?

Yes, there are other drugs these patients can take.

Do you expect to see labeling changes for other companies’ hepatitis C drugs—is the FDA getting reports of adverse events?

You’d have to ask those companies, but we are aware of some reports.

How different are all these antivirals?

They have different compounds that work on different steps in the virus’ replication cycle.

There are at least two companies that have “pan-viral” hepatitis C drugs coming to market, ones that work on all genotypes. Is AbbVie working on such a drug?

We expect to have one by the end of 2017.

Why do you suppose it was only your drug that caused these problems?

The labelling change was based on spontaneous reports from physicians. The information is limited and it is impossible to establish a causal relationship.

Were these patients who should not have been taking the drug in the first place?

A number were in patients where Vikiera was not recommended. Some were likely Child-Pugh C.

Physicians who attended the European Association for the Study of the Liver conference in Vienna earlier this year were very excited about these drugs—were they too excited?

No. The excitement is very much warranted. It is very good that we have these drugs, but there are populations who should not receive them—a small minority of patients with hepatitis C.

Do you consider this a setback?

Certainly safety is paramount and this is a safety issue and we are reaching out to communicate the changes broadly.

The drugs are not recommended for Child-Pugh C. What can you say about the potential mechanism of injury for those patients were they to take the drug—is it a matter of the liver being unable to clear the drug?

We did not do clinical trials [of the drugs] with these patients but we did find that in patients with Child-Pugh A and Child-Pugh B there were similar levels in the blood, but in Child-Pugh C idrug levels were higher.

Anything you’d like to add?

It is important that these drugs are not recommended to patients with hepatic decompensation.The labelling change is important but limited. Patients with Child-Pugh B and C are contraindicated for Viekira Pak and Technivie.