Herceptin has been a hugely successful drug. Brought to market in 1998 by Roche for the treatment of breast cancer, oesophageal cancer and stomach cancer, it has yielded sales of over $6 billion annually and was the world’s fifth largest selling drug in 2017.
Approximately 15-20% of all breast cancer patients have tumours that are HER2-positive. These tumours tend to grow more quickly than those that are HER2-negative. Prior to the launch of Herceptin, the prospects for patients with this form of cancer were pretty bleak, but this treatment has revolutionized life expectancy and quality for patients. The monoclonal antibody therapy was Roche's first targeted cancer drug, and it has dominated the HER2-positive market ever since, with market share still well above 90%.
Yet, in July 2014 the main European patent for Herceptin expired, and in 2019 some of the patent protections within the US will come to an end. The generic name for this antibody therapeutic is trastuzumab, and as it comes off patent there is huge potential for a highly lucrative market in biosimilars for this drug. Many of these are already in development. Indeed, a partnership between Mylan and Biocon has already launched a biosimilar of this drug, Canmab, in India, and in South Korea another biosimilar, Herzuma, has been brought to market by Celltrion. Once all the major patents for Herceptin have expired, it is expected that a number of other launches will follow. This will trigger price reductions for the drug and increase market access.
As the number of biosimilars for trastuzumab in development increase there is a need for tools to be able to monitor these potential new drugs accurately within patients, throughout the clinical trials process. With speed to market proving critical for the success of many new drugs, delaying development through problems arising with these bioanalytical assay reagents is not desirable.
Assay reagents for use in pharmacokinetic (PK) assays must be highly sensitive, specific, selective and show good reproducibility. They must accurately quantify the levels of an antibody therapeutic within patient samples, against a background of natural antibodies present within the serum. These anti-idiotypic (anti-ID) reagents must show good lot-to-lot reproducibility to ensure that assay results are standardised and reliable over the course of the drug development life cycle.
Monoclonal and recombinant antibodies and antibody fragments have been used successfully as PK assay reagents, but raising a specific antibody via immunisation requires long timeframes and often once selected these tools require affinity maturation to increase their performance within the assay environment. This can add significant time extensions to the development of projects.
We have applied Affimer technology to the development of anti-ID reagents and been able to generate and validate the use of an anti-ID binder to trastuzumab within a PK assay in just three months. This anti-trastuzumab binder is entirely specific to the trastuzumab antibody target, shows no matrix effects and is highly reproducible lot-to-lot.
When the performance of this binder was analysed by Covance, a leading CRO, as part of their assay validation studies, they showed that it met with the regulatory criteria for bioanalytical assay reagents and showed an increased dynamic range compared to current regulatory assays. The use of an increased dynamic range within an assay is important, as it reduces the need for repetition of sample analysis due to concentration differences, so reducing the assay-associated costs.
These studies demonstrate the benefits of Affimer proteins as applied to anti-ID tools and show the potential for their use as critical assay reagents for PK assays in the development of biologics.