MIV-818 for the treatment of liver cancer

Introduction

Liver cancer is the second highest cause of cancer- related death worldwide. Of the different forms of liver cancer, hepatocellular carcinoma (HCC) is the most prevalent. Medivir is developing drugs to deliver cancer therapeutics to the liver to treat this devastating disease.

Mechanism of Action

Current approaches to managing intermediate stage HCC, such as Trans-Arterial Chemo-Embolization (TACE), rely to a large extent on the targeting of drugs to the liver. Medivir has developed technologies that have been proven to selectively deliver the active metabolites of nucleoside and nucleotide analogues to the liver, based on its long-standing interests in discovering improved treatments for chronic hepatitis B virus and hepatitis C virus infection. For example, oral administration of MIV-802, Medivir’s nucleotide analogue for the treatment of HCV infection that has been partnered with Trek Therapeutics, gives exposures of the active drug in the liver that are 100x greater than in other organs. This technology has now been applied to liver cancer, and MIV-818 has been developed as an orally administered therapeutic with a high level of anti-tumour activity that is targeted for delivery to the liver. The intention is to maximize delivery of the drug to the tumour or tumours, while minimizing the systemic toxicity caused by exposure of MIV-818 and its metabolites to the rest of the body. The objective is to combine the benefits of the liver-targeting of TACE with the convenience of an orally administered pharmaceutical that does not require admission to hospital.

Disease area

Liver cancer is the second leading cause of cancer-related death worldwide, and one of the fastest growing cancers in the US, based on incidence and mortality. Hepatocellular carcinoma (HCC) is the most common cancer of the liver. Risk factors for HCC include chronic infection with the hepatitis B or hepatitis C viruses, metabolic diseases such as non-alcoholic steatohepatitis (NASH) and diabetes, as well as use and abuse of alcohol and tobacco.

Project overview

Many chemotherapeutic drugs that are successfully used to treat other cancers have failed to show efficacy in patients with HCC, often because severe adverse effects of the drug in the liver and elsewhere in the body prevent therapeutic drugs levels from being reached in the liver. One successful approach that circumvents this problem is known as TACE, a surgical procedure that targets chemotherapeutic agents to the tumour and blocks its blood supply, while limiting drug exposure elsewhere. This allows the chemotherapeutic drug to be delivered at effective concentrations in the liver while reducing systemic toxicity. This procedure has been shown to benefit patients with intermediate stage HCC, but is technically challenging, risky and has some restrictions that prevent its use in a large proportion of patients.

The only approved therapy for advanced HCC is the multi-targeted kinase inhibitor sorafenib (NexavarTM). Clinical studies show that patients receiving this treatment had a mean overall survival (OS) of approximately 11 months, compared 8 months among patients who received placebo. Following disease relapse, there is no recommended treatment available today. Taken together with the poor overall prognosis for patients diagnosed with intermediate and advanced HCC, there is a tremendous unmet medical need in the treatment of this devastating disease.

MIV-818 is in non-clinical development with the current aim to perform the safety studies required for the initiation of the first clinical study.

MIV-818 – Poster presentation at The American Association for Cancer Research Annual Meeting, April 2017 (PDF)

Page updated 19 April 2017