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HBV Foundation DrugWatchWednesday, May 05, 2010Hepatitis B drugs in development Introduction After a burst of hepatitis B virus (HBV) drug discovery and development over the last decade, the year 2010 saw the development pipeline dry up. While several currently available drugs are highly effective at controlling viral replication and keeping the disease in check, only about one-third of people are able to reach a key treatment goal: sustained viral control while safely off treatment. Life-long suppressive therapy with antiviral drugs appears to be the HBV treatment model for the near future for most people with chronic hepatitis B. Although antiviral drugs can control HBV, drug resistance may develop over time, leaving people with no treatment options. This is of particular concern as resistance can develop faster for people coinfected with HIV and HBV. Long-term toxicity is likely to be an issue. These concerns will not be resolved until there is a robust drug pipeline. Advances in basic science are needed to better understand HBV pathogenesis, identify new drug targets, and to stop HBV’s destructive track. Hopefully, the gradual expansion of access to health care will drive demand for new and better HBV treatment, and provide more financial incentives for the drug industry to invest in discovery and development of new compounds. In the meantime, there are no investigational new drugs in late stage development in the U.S. for HBV. Instead, the glimmer of hope—for what it’s worth—is coming from a handful of immune-based therapies, although these are all in early stage development. Oral antivirals Clevudine Despite Pharmasset’s halting U.S. development of clevudine due to post-market reports of severe myopathy (muscle weakness) last year, the South Korean drug maker Bukwang is forging ahead with development and marketing plans for clevudine in Asia. Studies in South Korea and a phase III trial in China are underway. Bukwang’s Asian partner, Eisai Pharmaceuticals, has launched clevudine (brand name: Revovir) in the Philippines, with pending licensing plans for India, Indonesia, Malaysia, and Thailand. It will be up to doctors and regulatory authorities in these countries to keep a close eye on reports of myopathy, since the condition can develop after eight months of clevudine use, and people must stop taking it to avoid potentially fatal consequences. In a rapid communication published in Hepatology (Seok 2009), the main symptom of clevudine induced myopathy was slowly progressive muscular weakness in the limbs over several months. The condition can take up to four months to resolve after clevudine is stopped. LB80380 LG Life Sciences published data from its safety and efficacy study of the new nucleotide analog LB80380 in Hepatology (Yuen 2010). The small study done in treatment-experienced Chinese volunteers with lamivudine-resistant chronic HBV showed potency comparable to entecavir and tenofovir, the two leading antivirals on the market. No significant drug-related toxicities were seen in this 12-week dose-finding study. A phase II study in treatment-naïve volunteers is enrolling in South Korea and Hong Kong. Tenofovir is the first-line treatment for lamivudine-resistant HBV in the U.S. and Western Europe. Resistance to tenofovir has not yet been characterized three years after the drug’s approval to treat HBV, but second-line drugs for people who become resistant to tenofovir may be needed in the future. Although LB80380 may be useful as a second-line drug for people with lamivudine resistance, an in vitro study revealed that LB80380 has only partial efficacy against adefovir and potential tenofovir resistant HBV strains. Development plans for the United States and Europe are unclear. Emtricitabine/Tenofovir This Gilead workhorse HIV combination pill is being studied in several ongoing HBV trials in different patient populations. Truvada is being studied in HIV/HBV coinfected people with a detectable HBV viral load despite current treatment, both in combination with pegylated interferon, and in a head-to-head comparison with entecavir. Trials are also underway in people with decompensated liver cirrhosis and liver transplant recipients. Lagociclovir Valactate (MIV-210)
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CYT107 A new entrant from the immune-based front is French company Cytheris’ recombinant human Interleukin-7 (CYT107). This immunomodulator is also being studied for HIV and hepatitis C. The CONVERT study will compare CYT107 with the HBV preventive vaccine GenHevac B versus CYT107 alone in HBeAg negative patients on stable tenofovir or entecavir treatment. This phase I/IIa study is enrolling volunteers in France and Italy. The hope is that the agent will stimulate the immune system and restore immune response to HBV so that people do not have to stay on life-long antiviral therapy. Several other immunomodulators and therapeutic vaccine candidates are currently in early phase development; however no study data have been published in the past year.
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© 2012 Hepatitis B Foundation UK |
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