Under the terms of the agreement, the two parties will develop, manufacture and commercialise ANA975 and additional Toll-Like Receptor 7 (TLR7) oral prodrugs for chronic HCV and HBV infections, as well as other infectious disease indications.
ANA975 is an oral prodrug of isatoribine, a small molecule TLR7 agonist that has been administered intravenously to 68 subjects in clinical trials. Results from multiple clinical trials in HCV patients receiving intravenous isatoribine for one week have demonstrated viral load reductions.
An ongoing phase I clinical trial of ANA975 indicated a bioavailability of 100 per cent with a rapid conversion to isatoribine in plasma. The trials also showed levels of isatoribine delivered to be clinically relevant. Anadys and Novartis expect to initiate a 28-day study of ANA975 in HCV patients in the second half of 2005.
According to the World Health Organisation, more than 2 billion people alive today have been infected with HBV at some time in their lives. Of these, about 350 million people remain chronically infected and become carriers of HBV.
Over 4 million acute cases of HBV develop each year and about 25 per cent of these cases result in death each year due to chronic HBV or related conditions, including cirrhosis and liver cancer.
Under the terms of the agreement, Novartis will make an initial license payment of $20 million to Anadys. Anadys is also eligible to receive up to $550 million in regulatory and commercial milestone payments based on the successful development and commercialisation of ANA975.
A $10 million payment is due following a successful Investigational New Drug (IND) submission, which Anadys expects to file with the US Food & Drug Administration (FDA) in the middle of 2005.
"This agreement is a further step in our strategy to augment internal activities with externally sourced products in key therapeutic areas such as HCV and HBV," said Thomas Ebeling, chief executive officer of Novartis.
Hepatitis C virus causes inflammation of the liver and degradation of liver function. Approximately 70 per cent of individuals infected with HCV progress to chronic hepatitis. The most common symptoms of chronic hepatitis, which may show no symptoms for many years, include an enlarged liver and spleen, jaundice, muscle wasting, excoriations (the result of scratching), ascites (swelling of the abdomen) and swelling of the ankles.
In total, HCV causes 10,000 to 12,000 deaths a year in the US, and the Centres for Disease Control, or CDC, estimate the annual mortality rate could increase to 38,000 by the year 2010, surpassing the number of deaths attributed annually to HIV/AIDS.
Additional terms of the agreement will see Novartis make an initial license payment of $20 million to Anadys. Anadys is also eligible to receive up to $550 million in regulatory and commercial milestone payments based on the successful development and commercialisation of ANA975. A $10 million payment is due following a successful Investigational New Drug (IND) submission, which Anadys expects to file with the FDA in the middle of 2005.
"Results of our clinical studies suggest that TLR7 agonists may represent an important new advance in anti-infective therapies," said Kleanthis Xanthopoulos, Anadys' president and chief executive officer.
"Together we hope to realise the potential of TLR-based therapies," he added.
Current treatments for HBV include interferon-alpha therapy, lamivudine and adefovir, but suffer from significant limitations as long-term therapies, including the many side effects associated with interferon treatment, the potential for renal toxicity associated with adefovir, and the emergence of HBV varients resistant to lamivudine treatment.
Significant unmet needs remain for improved HBV therapies for the more than 350 million people chronically infected with HBV.
The current standard of care for chronic HCV is a combination of an interferon-alpha product and ribavirin. Sales of HCV drugs are expected to grow due to improved market penetration through increased awareness and improved diagnosis rates and therapies.
Interferon-alpha is administrated by injection and results in abnormally high levels of this cytokine circulating systematically throughout the body. Therapy with interferon-alpha causes a number of side effects, including depression and flu-like symptoms.
In addition to the side effects, current therapies do not provide sustained elimination of the virus, or sustained virologic response, for 47-54 per cent of the treated patients when measured six months after the end of treatment.
Due to the lack of alternative treatments, patients without a sustained virologic response have no other treatment option but to undergo a second 48-week course of interferon-alpha based therapy with a different brand of interferon-alpha. This second course of therapy subjects the relapse patient to a similar risk of side effects as the previous course of therapy.