Interferon-Free C

Hep Talk by Larry Buhl

<strong>Warp Speeds <p>
CROI researchers predict oral-only interferon-free treatment by 2014</strong><p>
<a href=””><img src=”” alt=”warp_speed” width=”600″ height=”450″ class=”alignleft size-full wp-image-7443″ /></a><p>

Advances leading to new interferon-free treatments for hepatitis C were unveiled at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in March in Atlanta as researchers described results of next-generation direct-acting antiviral agents for both HCV monoinfected and HIV/HCV coinfected people.<p>
Direct-acting antiviral agents, available for fewer than two years, have ushered in a new era of treatment for chronic hepatitis C. But many patients and clinicians are waiting for all-oral regimens that don’t require interferon, must be injected weekly, and often causes difficult side effects such as flu-like symptoms and depression.<p>
These breakthroughs leading to all-oral regimens are significant because they will allow many more people to benefit from direct-acting antiviral drugs for HCV. Below are just four of the most encouraging results from interferon-free studies unveiled at CROI:<p>

<strong>Sofosbuvir and Ribavirin work well for harder to treat HCV patients.</strong> Investigators tested a simple 2-drug interferon-free regimen in a small Phase 2a study of difficult-to-treat patients in high-poverty inner-city neighborhoods of Washington, D.C., where patients had limited access to health services. The SPARE Study evaluated Gilead Sciences’ nucleotide analog HCV polymerase inhibitor sofosbuvir (formerly GS-7977) plus ribavirin. A simple 24-week, all-oral regimen of sofosbuvir plus full-dose ribavirin cured nearly seventy percent of previously untreated people with genotype 1 chronic hepatitis C, many of whom had factors predictive of poor response.<p>
<strong>Interferon-free combos cure most newly treated HCV patients.</strong> Eric Lawitz from the University of Texas Health Science Center and colleagues compared various interferon-free combinations of direct-acting drugs being developed by AbbVie (formerly Abbott). Their research found that all-oral regimens containing the HCV protease inhibitor ABT-450, a non-nucleoside polymerase inhibitor, and ribavirin led to sustained response for more than ninety percent of previously untreated patients, including those with unfavorable IL28B gene patterns, but only about half of prior non-responders. <p>
<strong>Sofosbuvir, Ledipasvir, and Ribavirin combo produces 100 percent sustained response.</strong> In the ELECTRON trial, sponsored by Gilead Sciences, investigators initially tested a simple twelve-week regimen of Gilead’s once-daily nucleotide analog HCV polymerase inhibitor sofosbuvir plus 1,000–1,200 mg weight-based ribavirin for previously untreated people with easier to treat HCV genotypes 2 or 3. An interferon-free regimen of the direct-acting hepatitis C drugs sofosbuvir (formerly GS-7977), ledipasvir (formerly GS-5885), and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100 percent for both treatment-naive patients and prior non-responders with HCV genotype 1.<p>
<strong>Simeprevir plus Sofosbuvir shows good early cure rate with or without ribavirin.</strong> This all oral combination led to an early cure for most hard-to-treat prior null responders with genotype 1 hepatitis C studied in the Phase 2a COSMOS trial. “Simeprevir plus sofosbuvir with or without ribavirin for twelve weeks yielded high SVR rates in prior null responders with mild-to-moderate fibrosis,” the researchers concluded.<p>

At a press conference on hepatitis C research, investigators gave projections about forthcoming approvals of direct-acting antiviral agents. David Thomas from Johns Hopkins predicted that the first components of interferon-free therapy would likely be approved by the FDA by the end of 2013. That would be a blazingly fast development time. <p>
Comparing the hepatitis C drug development timeline to HIV, Thomas said, it’s as if we’re going from Crixivan to Atripla in under two years. “We’re going from the first direct-acting agents that have horrible toxicity and are difficult to take into regimens that are safe and tolerable and in our case, the infection—in a year and a half.”<p>
“It’s like HIV drug development at warp speed,” said Douglas Dieterich. “It’s a really good time to have hepatitis C,” he added, with tongue slightly in cheek. <p>

Larry Buhl is a radio news reporter, screenwriter, and novelist living in Los Angeles. His young adult novel, The Genius of Little Things, debuted in January 2013. His comic mystery novel, We’re Here to Help, will be available later in 2013.