MIV-210 against hepatitis B

yuer

MIV-210 against hepatitis B – activities in 2001In vitro experiments proved that MIV-210 is active against lamivudine-resistant HBV. Comparative studies in in vivo models demonstrated MIV-210’s superior efficacy over lamivudine (the market’s currently predominant HBV pharmaceutical). In vitro trials demonstrated that MIV-210 also is effective against multiresistant HIV. Methods to produce the pharmaceutical grade MIV-210 were enhanced, resulting in better yields and reduced production costs. The pharmaceutical has been formulated in capsules for phase I trials; development of a tablet formulation commenced.Current phase I trials have demonstrated the compound’s very good oral uptake, when administered as capsules. No drug-dependent side-effects were demonstrated.

2002-09-30:
Positive results for Medivirs’s HIV and hepatitis B antiviral MIV-210 presented at ICAAC
Medivir’s antiviral MIV-210 is active against HIV and HBV (hepatitis B virus, viral jaundice) and is in phase I clinical trials. The compound has a promising profile in several respects compared with antivirals already on the market and projects in the pipeline. Medivir has presented new data on MIV-210 in the HBV and HIV indications at the ICAAC meeting (Interscience Conference in Antimicrobial Agents and Chemotherapy) currently underway in San Diego, USA.

MIV-210 is a nucleoside analogue and is patented to 2018. A number of preclinical studies have been run in parallel with the clinical trials, and some of these have now been completed. The aim of these studies has been to confirm the utility of MIV-210 as a pharmaceutical against both HBV and HIV and promising results have been obtained.

The Presented Results
A phase I clinical trial has shown that MIV-210 administered to healthy volunteers has a very good oral bioavailability (ie it can be administered as tablets) and achieves high blood plasma levels. Phase I clinical trials with repeat dosing will now be finalised and evaluated.

The activity of MIV-210 against HBV has been investigated in cell culture, where MIV-210 has also proven to retain activity against HIV, which has become resistant to the market’s current gold standard lamivudine. Such resistance arises during extended treatment of HBV patients with lamivudine.

MIV-210 has also been evaluated in woodchucks. These animals often have a natural, chronic infection with a hepatitis virus, which is extremely similar to human HBV. Treatment of woodchucks with chronic viral hepatitis is the current best known model for evaluating new HBV antivirals. In this model, MIV-210 reduces the amount of hepatitis virus in the blood to less than one ten-millionth of the pre-treatment levels.

In around 20% of the treated animals, this effect continued beyond the cessation of therapy, which no other antiviral has managed to achieve in this model. Additionally, the amount of virus in the liver was reduced to one thousandth of the pre-treatment level. No potential side effects were noted during the 10 week treatment or 8 week follow-up periods.

In comparison to the currently marketed HBV antivirals or those in the pipeline, MIV-210 stands out as a promising compound. As with HIV treatment, HBV treatment will demand combinations of different antivirals. In contrast to HIV, a proportion of HBV patients can be cured from the disease. This proportion is likely to increase as new, more potent antivirals and combinations reach the market.

MIV-210 is also active against HIV, both in cell culture and in in vivo models. New results show that MIV-210 has a unique resistance profile and retains its activity against HIV which has become resistant against all relevant antivirals on the market.

Bottiger et al., abst 148, and Harmenberg et al., abst. 150 described efficacy studies of MIV-210, an orally active pro-drug of 3'-fluoro-2', 3'-dideoxyguanosine (FLG), an active HBV and HIV inhibitor active against 3TC (lamivudine)-resistant viruses. In the duck hepatitis model, MIV-210 applied for 19 days at 10mg/kg reduced HBV plasma DNA by 2.5 log10. Rebound of virus was seen at the termination of treatment. In phase I single dose clinical trials, MIV-210 was well tolerated and showed a rapid oral uptake and the rapid conversion to the active antiviral compound, FLG. The half-life of FLG was 1.5 to 2.3 hr, with 80% renal clearance. MIV-210 appears to have good potential for further clinical development.

MIV-210: an Antihepatitis B and HIV Compound with Unique Resistance Profile
Researchers at Medivir AB, Sweden will present results from an evaluation of MIV-210, an inhibitor of hepatitis B virus (HBV) and HIV at the 15th International Conference on Antiviral Research held in Prague. The nucleoside analogue MIV-210 inhibits HBV and HIV in cell culture and in vivo: Both HIV and HBV develop resistance to present therapies but MIV-210 shows effect against such resistant virus in cell cultures.

In a hepatitis B in vivo model MIV-210 shows a more potent effect than lamivudine, the only antiviral drug presently on the market for hepatitis B treatment. In an in vivo model for HIV infection MIV-210 is about 10 times more potent then zidovudine.

Phase I pharmacokinetic single dose study in human volunteers showed that MIV-210 has a high oral bioavailability and no side effects were observed.

Presently a study on the effect and safety of MIV-210 in WHBV-infected woodchucks is ongoing.

Medivir's MIV-210 Enters Phase I Multiple Dose Study
HUDDINGE, Sweden, Feb. 7, 2003 (PRIMEZONE) -- The continued phase I clinical study, multiple dosing in healthy volunteers, for the antiviral MIV-210 has now started. The study is being performed in the United Kingdom and is expected to be completed during the second half of 2003.
The goal of the study is to further ensure the compounds safety after multiple oral dosing and to further investigate its good oral bioavailability and pharmacokinetic properties to establish dose levels for entering phase II trials.
MIV-210 is a polymerase inhibitor effective against both multiple drug resistant HIV-1 and hepatitis B (HBV) in vitro and in vivo. The development plan for the compound includes clinical phase II studies in both HIV and hepatitis B patients. Medivir (Stockholm: MVIRb.ST - news) has a second drug in clinical development targeting multidrug resistant HIV-1, namely MIV-310 (alovudine) which is in clinical phase II. MIV-210 and MIV-310 have shown synergistic effects against HIV-1 in vitro.
There are more than 1.5 million of HIV/AIDS patients in the Western world of whom a considerable portion harbour drug resistant HIV-strains. The number of patients with multiresistant HIV is increasing rapidly and there is a considerable need for new antivirals. Current HIV therapy employs combinations of several antivirals from different classes with different resistance profiles. MIV-210 has in vitro been found to inhibit HIV-1 strains that are resistant to other polymerase inhibitors. Sales of polymerase inhibitors against HIV-1 amounted to $3.5 billion US during 2001.
There are more than 350 million chronically infected hepatitis B patients worldwide, of whom 5-6 million are in the Western world and approximately 100 million are in China. The number of patients treated is comparatively low but growing rapidly as new antivirals are introduced. The emergence of HBV strains resistant to the available medications will increase the need for new antivirals. Sales of HBV antivirals in 2001 were approximately $0.6 billion US despite their limited efficacy.
The Medivir Group
Medivir is an innovative and specialized research company active in the pharmaceuticals sphere, located in Cambridge, U.K., and Huddinge, Sweden. Medivir's research focuses on the development of new pharmaceutical compounds as inhibitors of target enzymes with protease or polymerase activity.
The group comprises Medivir AB, the subsidiaries Medivir UK Ltd. and CCS AB, plus second-tier subsidiaries CCS (UK) Ltd. and Nordic Care Sweden AB. Medivir has been listed on the Stockholm Stock Exchange since 1996.
The research portfolio includes projects against HIV, viral hepatitis, shingles, cold sores, osteoporosis, rheumatoid arthritis, asthma, multiple sclerosis and organ/graft rejection. Medivir has four projects in clinical development. Of these, two are moving towards Phase III trials after having completed Phase II trials. One is in Phase I and the other is in Phase II. Medivir's pre-clinical research encompasses a number of projects, of which one is in the late pre-clinical development stage and a further three are in, or are entering the lead optimization phase. Furthermore, ten activities are in the explorative stage.