3D Combo Works in Cirrhotic HCV Patients, Too

A drug combination with striking efficacy in relatively healthy hepatitis C (HCV) patients had similar outcomes in patients with compensated cirrhosis, a researcher said.

In an open-label phase III trial, more than 91% of cirrhotic patients cleared the virus despite advanced disease, according to Fred Poordad, MD, of the University of Texas Health Science Center in San Antonio.

Patients in the trial were given 12 or 24 weeks of the so-called 3D drug combination, which had very high success rates in other HCV populations, Poordad reported here at the annual meeting of the European Association for the Study of the Liver and online in the New England Journal of Medicine.

But “cirrhosis remains hard to treat,” Poordad said, “even in the era of DAAs'” — the new direct-acting agents that target HCV replication. The so-called TURQUOISE study is the first DAA trial to include only patients with cirrhosis, he said.

“It’s an amazing study,” commented Jean-Michel Pawlotsky, MD, PhD, of the Henri Mondor University Hospital in Créteil, France, near Paris, who was not part of the trial but who moderated the session at which it was presented.

“It was a clean population (of cirrhotic patients),” he told MedPage Today, “with very good data and unexpectedly high SVR rates.”

SVR, or sustained virologic response, is shorthand for having no detectable virus; when it occurs 12 weeks after the end of treatment — the primary endpoint of most HCV trials nowadays — it is regarded as tantamount to a cure, since few patients relapse after having achieved that milestone.

Poordad and colleagues studied outcomes in 380 patients with genotype 1 HCV — the subtype of the virus that is most common in North America — and Child-Pugh class A cirrhosis.

The drug combination they used has been known until recently by its nickname, 3D, because the drugs involved had yet to be named by the manufacturer, AbbVie of North Chicago, Ill.

Two of them now have names — ABT-267, an NS5A inhibitor, is now ombitasvir and the non-nucleoside polymerase inhibitor ABT-333 is now called dasabuvir. The third drug is ABT-450, a protease inhibitor boosted with ritonavir (Norvir), and is nameless so far, although company spokesmen told MedPage Today a name should be picked soon.

ABT-450, ritonavir, and ombitasvir are co-formulated and given once daily, while dasabuvir is given twice a day. The combination is given with ribavirin, a nonspecific antiviral drug, also twice a day.

Patients in the trial, Poordad said, were randomly assigned to 12 or 24 weeks of the 3D combination and the primary endpoint was SVR12, compared with an estimated historical cure rate of 47% with a regimen of telaprevir (Incivek), pegylated interferon-alfa, and ribavirin.

Overall, he reported, patients did very well — 191 of 208 patients, or 91.8%, in the 12-week arm reached an SVR12, as did 165 of 172 patients, or 95.9%, in the 24-week arm.

The rates were markedly superior to the historical control rate, Poordad said.

The numbers compare well with the rates reached in two other trials presented here involving healthier patients and the 3D combination — SVR12s in the so-called SAPPHIRE studies ranged from 95.3% to 100% depending on patient subgroups.

The SVR12 rates were high and consistent regardless of treatment duration across almost all subgroups, Poordad said, including those with previous treatment failures. Specifically, there was no apparent difference in response according to such things as race, body mass index, baseline HCV RNA level, platelet count, or serum albumin level.

The only fly in the ointment was the subgroup of patients with genotype 1a infection who had previously not responded to treatment with an interferon-based regimen.

Among those patients in the 24-week arm, 39 of 42 reached SVR12, (92.9%). But in the 12-week arm, just 40 of 50 patients (80%) reached the milestone.

In contrast, all of the null responders with genotype 1b infection reached SVR12, regardless of the treatment duration, he said.

If the combination is approved, physicians treating prior null responders with genotype 1a HCV might “err on the side of treating them a little bit longer,” Poordad said.

The 3D combination was well tolerated, Poordad said. The most common adverse events were fatigue, headache, and nausea, and were higher in the 24-week arm.

The hemoglobin level was less than 10 grams per deciliter (an expected side effect of ribavirin) in 7.2% and 11% of patients in the 12- and 24-week arms, respectively.

Overall, 2.1% of patients dropped out of the study because of adverse events, Poordad reported.

Reposted from MedPage Today on January 10, 2015: www.medpagetoday.com/MeetingCoverage/EASL/45245

Author Info

Sean Hendrickson