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Generic hep C drugs as effective as high-cost brand names, plus other European Liver Conference highlights

, by Liz Highleyman

Refining and expanding access to hepatitis C treatment was a major focus at the International Liver Congress, presented by the European Association for the Study of the Liver (EASL) last month in Barcelona.

Experts estimate that 3 to 5 million people in the U.S. and approximately 130 to 150 million people worldwide are living with hepatitis C. Over years or decades, chronic hepatitis C virus (HCV) infection can lead to severe liver disease including cirrhosis, liver cancer, and the need for a liver transplant.

New surveillance data released this month in by the Centers for Disease Control and Prevention found that the number of hepatitis C-related deaths in the U.S. is at an all-time high—with a total of 19,659 reported in 2014—and exceeds deaths attributable to 60 other infectious diseases including HIV and tuberculosis.

Optimizing Hepatitis C Therapy

The development of interferon-free direct-acting antiviral (DAA) therapy has brought about a revolution in hepatitis C treatment in recent years. Unlike the old interferon-based therapy, which took six to 12 months, caused difficult side effects, and only cured about half of people who tried it, the new DAAs can cure more than 90% of patients in just three months.

With several DAA regimens now available, the focus has shifted to “refinements and gaining experience” using these drugs in the real world, according to EASL vice secretary Tom Hemming Karlsen, MD. This includes optimizing treatment for challenging patient groups such as people with advanced liver cirrhosis, those with hard-to-treat HCV genotype 3, and those not cured with prior treatment. Research highlights were, as follows.

Therapy for treatment-experienced people with all HCV genotypes  

Researchers reported that a triple combination of Gilead Sciences’ sofosbuvir (Sovaldi), velpatasvir, and GS-9857 demonstrated near-perfect (98%-99%) sustained response rates for treatment-experienced patients with all HCV genotypes.

Therapy for HIV-positive people coinfected with HCV genotypes 1 – 4

A dual regimen of sofosbuvir plus velpatasvir was highly effective against HCV genotypes 1 through 4 in HIV-positive people with hepatitis C coinfection, producing a cure rate of 95%.

Therapy for adolescents

The already-approved sofosbuvir/ledipasvir (Harvoni) combination was shown to work as well for adolescents with hepatitis C as it does for adults.

Therapy for “difficult-to-treat” people

AbbVie’s pipeline candidates ABT-493 and ABT-530 were shown to be highly effective for difficult-to-treat patients, with a 97% sustained response rate for people with HCV genotype 3 and liver cirrhosis, and 95% for people with genotype 1 who did not respond to previous treatment.

Katja Deterding

Katja Deterding, MD (Photo: Liz Highleyman)

Therapy for recent HCV infection

Turing to acute HCV infection, Katja Deterding, MD, from Hannover Medical School reported that just six weeks of sofosbuvir/ledipasvir appears to be enough to cure people with recent infection—at least those who are HIV-negative. A similar study presented at the recent Conference on Retroviruses and Opportunistic Infections, however, found that some HIV-positive people relapsed after such a short treatment duration.

Benefits of Hepatitis C Treatment

Curing hepatitis C can reduce the risk of liver disease progression and may even reverse some liver damage. But a Spanish study presented at the conference showed that direct-acting antivirals may not significantly improve liver function, eliminate the need for transplantation, or prolong life in people with the most severe decompensated cirrhosis—underlining the importance of not waiting too long to start treatment.

Another study found that hepatitis C patients with cirrhosis who were successfully treated still had an unexpectedly high risk of liver cancer, showing the need for ongoing liver cancer monitoring and, again, the importance of starting treatment before cirrhosis develops.

Along with slowing liver disease progression, successful treatment has the additional benefit of stopping onward transmission of HCV, a concept known as “treatment as prevention.”

Hepatitis C reinfection after successful treatment remains a concern, including re-infection due to sexual transmission. One study reported at the conference found that a quarter of HIV-positive gay men who cleared their initial HCV infection were re-infected within three years. But according to a mathematical model presented by Natasha Martin, PhD, from the University of California at San Diego, HCV sexual transmission could be dramatically reduced by scaling up treatment.

Discussing forthcoming EASL hepatitis C treatment recommendations, guidelines panel members agreed that treatment should not be limited for people who become re-infected. Geoffrey Dusheiko, MD, from the Royal Free Hospital in London suggested that people who are reinfected should actually be prioritized for retreatment because they are likely to be potential HCV transmitters.

Expanding Access Worldwide

With the medical mysteries of hepatitis C now largely solved, expanding access to treatment remains a goal in the U.S. and worldwide. Due to the high cost of the new DAA drugs, many government payers and private insurers have restricted access to the sickest patients.

But generic versions of some of these medications are starting to become available and may help expand treatment access to more people.

Australian physician James Freeman, MD, reported on a study finding that low-cost generic drugs are as safe and effective as brand-name products.

Freeman agreed to monitor more than 100 hepatitis C patients who obtained generic sofosbuvir, sofosbuvir/ledipasvir, or daclatasvir (brand name Daklinza) through the online FixHepC buyer’s club. Buyers initially imported active pharmaceutical ingredients from China and had them formulated into pills, and later obtained generic pills from India and Bangladesh. The generic regimens cost around $1,500 compared to as much as $150,000 for a full course of therapy without discounts in the U.S.

Preliminary data showed overall sustained response rates of 90% to 100% at four weeks post-treatment, similar to those observed at 12 weeks post-treatment in clinical trials of the corresponding brand-name drugs. Freeman stressed that it is important for people seeking generic hepatitis C therapy to undergo medical monitoring.

Laurent Castera, MD (left) and Jean-Michel Pawlotsky (right) at the International Liver Conference (Photo: Liz Highleyman)

Laurent Castera, MD (left) and Jean-Michel Pawlotsky (right) at the International Liver Conference (Photo: Liz Highleyman)

“There is a clear role for generic treatments such as these for people with hepatitis C across the world,” commented EASL secretary general Laurent Castera, MD. “The implications of increased availability of these drugs could be enormous, presenting more people with the possibility of a cure for what is often a debilitating condition.”

In addition to the high cost of treatment, a global shortage of liver disease specialists is another barrier to scaling up hepatitis C treatment. But the ASCEND study found that treatment managed by non-specialists can be equally safe and effective.

Sarah Kattakuzhy, MD, from the University of Maryland reported that patients assigned to receive treatment managed by a primary care physician or nurse practitioner were as likely to be cured as those who were treated by hepatologists or infectious disease specialists. In fact, treatment adherence was better among patients treated by nurse practitioners.

“This research has the potential to be a genuine game changer in the way we look at HCV treatment across the board, and could provide the opportunity to increase access to care and treatment to many regions of the world,” Karlsen commented.

Given the high cure rates of DAA therapy, scaling up treatment has the potential to halt the hepatitis C epidemic.

According to a recent report from the National Academies of Sciences, Engineering, and Medicine, hepatitis B and C could be eliminated as a public health threat in the U.S. by treating more people in order to end transmission and prevent progression of liver disease and liver-related death.

viral hepatitis statement

Javier Brahm, Jinlin Hou, Keith Lindor and Laurent Castera sign the viral hepatitis elimination statement (Photo: Liz Highleyman)

At the opening session of the International Liver Congress, leaders of liver disease associations from the U.S., Europe, Latin America, and Asia released a joint statement on elimination of viral hepatitis, calling for enhanced efforts to diagnose and treat hepatitis B and C.

The joint endorsement sends an “incredibly strong signal to the world” that leading scientists think elimination of viral hepatitis is achievable,” said Gottfried Hirnschall, MD, director of the World Health Organization (WHO) Global Hepatitis Program. “What we need now is increased advocacy to make sure plans turn in to real action.”

In conjunction with the conference, WHO released updated guidelines for hepatitis C screening and treatment, which are “intended to promote the scale-up of HCV treatment, particularly in low- and middle-income countries where few people currently have access to hepatitis treatment, despite also being where most people with HCV live,” according to a WHO statement.

In addition, EASL previewed its updated hepatitis C guidelines which, like the U.S. guidelines developed by the American Association for the Study of Liver Diseases and Infectious Disease Society of America, recommend that nearly everyone with hepatitis C be considered eligible for treatment, regardless of liver disease stage.

EASL guidelines panel member Massimo Puoti from Ospedale Niguarda Ca’ Granda in Milan emphasized that all hepatitis C patients should be treated except those with a short life expectancy due to other causes, in consideration of both individual health and the public health benefit of preventing HCV transmission.

“Every hepatitis C patient has a right to be treated,” guidelines coordinator Jean-Michel Pawlotsky concurred.

Liz Highleyman is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.


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