Professor Anton Hagenbeek, a haematology specialist based in the Netherlands who has been conducting clinical trials of HuMax-CD20 (ofatumumab), showed the latest data at the European Haematology Association congress, recently held in Vienna, Austria.
He also explained how GSK hopes the drug will break into a well established market.
As reported by DrugResearcher.com , HuMax-CD20 was the subject of the world's biggest licensing deal when GSK agreed to pay developers Genmab up to $2.1bn (€1.6bn) for the fully humanised monoclonal antibody (MAb).
As the name suggests, the drug acts by binding to the CD20 receptor on the surface of mature B-cells, activating an immune response against them.
These cells often malfunction or are overproduced in certain types of leukaemia, and it is hoped the antibody could be used to treat chronic lymphocytic leukaemia and follicular lymphoma.
However, there is already an antibody on the market that targets CD20 called Rituxan (rituximab).
This drug was developed by Genentech and approved almost a decade ago.
So the question is: why do we need a new CD20 antibody?
According to Prof Hagenbeek, although Rituxan has been a 'dramatic' success - it has been shown to increase survival by three years - only around 70 per cent of patients respond to the therapy while others become resistant to it or relapse early.
Since HuMax-CD20 binds to a slightly different part of the CD20, GSK hopes it could be used, initially at least, to treat these patients.
There have been many studies of Rituxan resistance with many theories being offered as to why some patients respond better than others.
The first set of theories is based on the target itself and includes loss of CD20, transient down-regulation of the target, genetic mutations and low antigen density.
Other theories include an increased cell suicide (apoptotic) threshold.
This could be due to overproduction or mutations in various proteins that reduce cell suicide, such as Bxl-xl FAS and TNF-related apoptosis inducing ligand (TRAIL).
Other possibilities include that the lymphoma cells themselves become resistant to drugs, through processes that inhibit the recruitment of immune system killers after Rituximab binding, and gene expression patterns.
A third possibility is that the problem could lie with the patient themselves - perhaps they metabloise the drug particularly fast, for example Which of these factors is at work, if not all of them, in a particular patient is unknown, although it is clear other CD20 antibodies could overcome some of them.
Compared to Rituxan, Prof. Hagenbeek explained that HuMax-CD20 binds more strongly to CD20 and stays on the target for longer.
This could be due to the fact that it binds to a different place on CD20 (although not far enough away that the two drugs could be used together).
It also shows stronger complement activity and similar antibody-dependent cellular cytotoxicity.
HuMax-CD20 is currently in Phase III trials.
Roche and Glycart Biotechnology are also collaborating on a CD20 antibody.
GA101 is a type II antibody (HuMax is type I), which has shown to offer increased levels of direct cell death and increased antibody-dependant cellular cytotoxicity also.
When asked if he thought HuMax will also suffer from resistance problems, Prof. Hagenbeek told DrugResearcher.com that: "We cannot rule that out but we are not yet in the position to be able to tell."
He added that although the drugs also destroy healthy B-cells, they don't appear to increase the number of infections patients suffer from.