Hepatitis C - albinterferon alfa-2b
The hepatitis C virus causes inflammation of the liver, but many patients remain symptom free for maybe two decades before the problems it causes appear. It can lead to cirrhosis, fibrosis, liver cancer and liver failure.
The hepatitis C virus causes inflammation of the liver, but many patients remain symptom free for maybe two decades before the problems it causes appear. It can lead to cirrhosis, fibrosis, liver cancer and liver failure.
The standard treatment is interferon-ÃŽ±, but this has a short half life of just two or three hours in humans, and so regular - and expensive - injections of the drug are required, maybe once a day for a year or more.
Modified interferons have been developed that have longer half lives, such as by pegylation, which increases the half life to 40-80 hours. This gives a better virological response, and the standard treatment is now a combination of this with the drug ribavirin.
However, many patients fail to respond to this or have significant side-effects, and several other interferon derivatives are under investigation. These include albinterferon alfa-2b, being co-developed by Human Genome Sciences and Novartis, which is made using albumin fusion technology. This involves fusing the gene that expresses human serum albumin to the interferon, resulting in a single polypeptide drug.1
A Phase I/II trial was carried out in 119 patients with chronic hepatitis C who had failed previous interferon-ÃŽ± treatment.2 In the multicentre open label, dose escalating trial, subjects were given 7-900µg of the drug in subcutaneous injections, either one dose or two 14 days apart. The most common side-effects were headache and fatigue, and a good response was seen in those given single doses of at least 40µg. Dose-related decreases in HCV RNA of at least 1 log10 IU/ml were seen in 47% of those given a single dose of at least 120µg, and 59% of those given at least 400µg in a double dose.
A further Phase II trial took place in 59 patients HCV patients who had never received interferon therapy.3 They were given two subcutaneous injections 14 days apart with doses between 200 and 1200µg. More than two-thirds of patients given 900 or 1200µg of at least 2 log10 IU/ml.
It is currently being investigated in a Phase IIb trial in 458 patients who had not previously been treated with interferon.4 They were given subcutaneous albinterferon alfa-2b in 900 or 1200µg doses every two weeks or the higher dose every four, or pegylated interferon alfa-2a, for 48 weeks. Both were given along with ribavirin, and the side effect profiles were similar for both groups. The best virological response was seen in the group given the highest dose twice a week. Phase III trials are under way.