July 15, 2013
When patients now tell me they want to get blood tests prior to hepatitis C therapy, that they want to be ready, it’s a new experience,” says hepatologistSaleh Alqahtani who’s unused to enthusiasm for treatment. Though present medication for the degenerative disease cures roughly 75 percent of patients who stay with it, “eager” isn’t a usual patient descriptor.
“The side effects of the drugs significantly alter quality of life for a number of patients. They stop medication prematurely or decline it altogether,” Alqahtani says, “especially if they’re asymptomatic.”
But major change is on its way, as he and colleagueMark Sulkowski are well aware. Long part of the drug-development pipeline through its clinical trials, Johns Hopkins is now waiting for a virtual outpouring of new, more patient-friendly hepatitis C antiviral agents, some as soon as this year. Already, Sulkowski, an infectious disease expert who directs the institution’s hepatitis trials, and Alqahtani, who oversees pre- and post-liver transplant patients, face new treatment protocol and policy questions.
For a decade, therapy has meant a combo of interferon and the broad antiviral, ribavirin. The regimen clears hepatitis C virus (HCV) in about half of those able to take it. Then, in 2011, companion drugs arrived. The first oral protease inhibitors—direct-acting drugs aimed at HCV’s reproducing machinery—added to what came before to raise cure rate dramatically, to some 80 percent.
Still, the benefit has come at a price. Patients face rashes and anemia from the newer drugs, fatigue and depression from the interferon.
So the good news from yet more pharma research last year was welcome. Researchers heralded a second generation of better protease inhibitors, all fresh from phase II and III trials. On top of that camesofosbuvir, a drug metabolized in the liver to yield an agent both potently disruptive of HCV and comparatively gentle to patients—even those with advanced liver disease.
After Sulkowski’s report of a late-phase trial of sofosbuvir plus one of the new protease inhibitors last fall at national meetings, the place was abuzz. More than 95 percent of patients tested negative for the virus. “HCV normally outruns the immune system, but now we can catch it and hold it down,” he says. “We can actually clear the virus to cure the disease.”
And, says Alqahtani, “for the first time in history, that cure doesn’t have to involve interferon.”
Progress is moving so fast for this and other combos that FDA approval should come (see box) within two or three years. Optimism shines as never before. The only immediate cloud is having to settle which new patients can safely wait for therapy until the government OK.
“That decision is especially complex for patients facing liver transplant for the disease,” Alqahtani explains. “You can’t reverse frank liver failure. And though hepatitis C is now the number one reason for U.S. liver transplants, the disease unfortunately recurs some time after transplant. What’s wonderful now is that data suggest clearing the virus before transplant makes that risk very small. Knowing that an interferon-free protocol is likely coming that’s both easier on patients and keeps their transplants healthy—it’s worth the wait.”
New HCV protocols—tested in Johns Hopkins trials— should soon see the light of day.
- sofosbuvir + ribavirin for genotypes 2,3 (2013)
- interferon + ribavirin + sofosbuvir for genotype 1 (2013)
— Courtesy Mark Sulkowski