NeuroVive's anti-viral preclinical program, with compound designated NVP018, has generated significant data indicating that NVP018 has the potential to become an effective alternative or addition to current drugs for treating chronic hepatitis B infections. This new data will be presented at the EASL (European Association for the Study of the Liver) congress in London, in April 2014 (www.ilc-congress.eu).
The results indicate that NVP018 has a dual effect against the hepatitis B virus. Firstly, the data generated suggests that NVP018 directly inhibits several stages in viral propagation in liver cells, and secondly, NVP018 also operates indirectly by strengthening the immune response. The data also indicates that the risk of developing resistance, a significant clinical problem with current therapy alternatives for hepatitis B, is very low with NVP018. Finally, NVP018 also demonstrates activity in an animal model of chronic hepatitis B infection.
According to the WHO, over 2 billion people have been in contact with the hepatitis B virus and 240 million people have developed chronic hepatitis B. This means that the disease is one of the largest global medical challenges. The chronic disease is estimated to cause more than 600,000 deaths yearly through advanced cirrhosis of the liver or primary liver cancer. The disease is worldwide, but most common in Southeast Asia, Eastern Europe and Africa, with over 8% chronic carriers. In Western Europe and the US, the frequency is less than 1%. Currently available pharmaceuticals display limited effectiveness and there is a significant risk of the virus developing resistance, so accordingly, there is a substantial need for new pharmaceuticals.
NVP018 is an oral preparation of NeuroVive's leading drug candidate in the company's new portfolio of cyclophilin inhibitors. The preclinical development program has demonstrated that NVP018 has unique characteristics that make it a promising anti-viral drug candidate and the new research results underscore NVP018's clinical potential for treating chronic hepatitis B infection.
"The results of the preclinical tests of NVP018, conducted by bodies including the prestigious Scripps Research Institute are very promising, with convincing data that cyclophilin inhibitors have a positive effect to hepatitis B virus infection. NVP018 is currently in a preclinical program, to be administered on patients at a later stage in clinical trials," commented Jan Nilsson, COO of NeuroVive.
it is difficult to estimate the potential of this cyclophilin inhibitor against hbv.
here is the easl abstract
NVP018, A CYCLOPHILIN INHIBITOR FOR TREATMENT OF CHRONIC HBV INFECTION
J. Nilsson1, S. Moss2, N. Coates2, M. Bobardt3, P. Gallay3, M. Gregory2
1Neurovive Pharmaceutical AB, Lund, Sweden, 2Isomerase Therapeutics Ltd., Cambridge, United Kingdom, 3The Scripps Research Institute, La Jolla, CA, United States
Background and aims: Whilst cyclophilin (Cyp) is a clinically validated target for chronic HCV infection, recent work has shown that inhibition of Cyps by either siRNA knockdown or therapeutically can also inhibit hepatitis B virus in vitro. NVP018 (previously known as BC556) is an orally available sangamide-based cyclophilin inhibitor (CI), with a well-differentiated preclinical profile when compared to cyclosporine-based CIs such as alisporivir and SCY-635. It has a very different structure and does not have the liabilities associated with these cyclosporine-based compounds.
Methods: Analysis of NVP018 viral inhibition, including mechanism of action studies and immune modulation in models of hepatitis B virus infection.
Results: NVP018 is a potent inhibitor of HBV replication distinct from previously studied inhibitors. It has a dual mechanism of action including both direct inhibition of viral pathways which require cyclophilins and immune modulation via IRFs, including potent inhibition of an interaction between cyclophilin A and IRF9, a key component of the Jak/Stat pathway.
Conclusions: NVP018 inhibits HBV infection in various models via new mechanisms and represents a novel combination partner for nucleotide inhibitors or interferons for treatment of chronic HBV infection, with the potential to inhibit viral replication and increase seroconversion rates.
This is about blocking the NTCP receptor by cyclosporin. The idea is to inhibit entry by blocking the hbv receptor. This is exactly what myrcludex is doing and doing it very well at high doses. The problem is that ntcp blockage can only be done mildly without causing a major bile acid toxic syndrome to the body. 20 to 40 grams of bile acids have to be re-transported every day from the portal blood into the hepatocyte interior. Most of this is done by the ntcp. So i cannot see a good future for ntcp blocking efforts, and myrcludex is already doing it, is a progressed stage, works very effectively and has no other toxicities, in particular since it enters no other cell types beyond hepatocytes.
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