Interferon-free regimen works against HCV in liver recipients

Last Updated: 2014-11-11

By Gene Emery

NEW YORK (Reuters Health) - Thirty three out of 34 liver transplant recipients who received an interferon-free drug combination for their recurrent hepatitis C virus showed a sustained virologic response after 24 weeks, according to an uncontrolled trial published online November 11 by the New England Journal of Medicine.

Patients received ribavirin, 250 mg of dasabuvir twice daily and a daily combination of 25 mg of ombitasvir, 100 mg of ritonavir, and 150 mg of ABT-450.

The regimen "was associated with a low rate of serious adverse events," said the team, led by Dr. Paul Kwo of Indiana University in Indianapolis.

The findings were also reported at a meeting of the American Association for the Study of Liver Diseases in Boston.

The treatment was tested in patients infected with recurrent HCV genotype 1, who are hard to treat.

AbbVie, based in North Chicago, Illinois, paid for the study.

"This is the first of a series of regimens coming online," said Dr. Dilip Moonka, medical director of Liver Transplant at Henry Ford Hospital in Detroit, who was not connected with the new study.

"It's going to have a huge impact because between 40% to 45% of the transplants in the U.S. are done for hepatitis C and the virus almost uniformly comes back. And it can be very aggressive," he told Reuters Health by phone.

With interferon therapy, "the cure rates are more like 60% but the regimens are very toxic," he said. "They're really dangerous. Patients can't tolerate them well. So to have an oral regimen that cured 97% of patients is just really, really important."

The open-label study, known as CORAL-I, was done on volunteers with recurrent HCV but without fibrosis, from 10 centers in the U.S. and Spain. They had not received any interferon-based therapy after the transplant. Patients with HIV or hepatitis B were excluded. The median time to treatment was three years posttransplant.

"By week four of treatment, HCV RNA levels had decreased to less than 25 IU/mL in all 34 patients," the Kwo team reported. After treatment ended, one patient had a relapse on Day 3. The rest had a sustained virologic response for 24 weeks after therapy ended.

"Thus far we've seen no additional relapses," said Dr. Kwo in a phone interview supervised by AbbVie. "The expectation is these patients will have durable responses to therapy."

Side effects included fatigue in 50% of the patients, headache in 44% and cough in 32%. The rates of anemia, diarrhea, insomnia, asthenia, nausea, muscle spasms and rash ranged from 20% to 30%.

There were no cases of graft rejection. Five patients needed erythropoietin; none needed a blood transfusion. Only one volunteer discontinued therapy because of rash, anxiety and memory problems.

The regimen is expected to be approved by the end of the year, according to an AbbVie spokeswoman who also said, "It's too early to speculate what the cost will be."

"I think in the posttransplant setting this has the potential to save money," said Dr. Moonka. "Between 30% to 50% percent of patients will develop cirrhosis and liver failure where they will die or require a second transplant, and a second transplant is incredibly expensive. But even if they develop liver failure, the care of these patients is incredibly expensive."

"In the general population it's a little more controversial because a lot of people will never develop problems with hepatitis C," he said.

Dr. Moonka noted that the "study chose patients that were fairly stable . . . They looked at patients with no fibrosis or mild fibrosis. The other thing that should be pointed out is that the regimen has a lot of drug interactions with the immunosuppressive drugs, so you have to be careful with that."

At the meeting, the company also presented partial results of an open-label study on patients with chronic hepatitis C and HIV who received the same oral regimen. In the test, known as TURQUOISE-I, 29 of 32 patients had a sustained virologic response at 24 weeks.

It also reported on a separate study, known as PEARL-I, in which all 91 patients with genotype 4 showed a sustained response at the 12 week mark whether they were new to hepatitis C therapy or previous interferon treatment had failed.

When ribavirin was excluded from the regimen, the 12-week response rate was 91%.

SOURCE: http://bit.ly/1zJzcaO

N Engl J Med 2014.