CLINICAL TRIALS
evaluated in clinical trials, but the recent draſt guidance on clinical pharmacogenomics from the US Food and Drug Administration (FDA) seeks to place this on a more formal footing. Te UK Technology Strategy Board’s Stratified Medicines Innovation Platform also aims to promote activity in this field.
Historically, heterogeneity in response to a drug has been a source of concern, but increasingly this may be viewed more as an opportunity. Stratification of a patient population may offer the promise of finding the patients that are really helped by a therapy, and potentially of being able to secure a patent position that reflects that selection and treatment approach.
Incorporating pharmacogenomics into clinical studies might be expected to identify populations who should receive different doses of a drug because of metabolic differences that may be identified by polymorphism in genes encoding metabolic enzymes, especially the cytochrome P450s. It may also identify responder populations, and populations at an increased risk of adverse events, based on their genetic characteristics. Each of these can potentially lead to patentable subject matter.
An example of genomic information affecting drug usage is the boxed warning on the product label for abacavir (Ziagen®). Patients who carry the HLA-B*5701 allele are at high risk of experiencing a serious and potentially fatal hypersensitivity reaction to abacavir. Screening for HLA-B*5701 status is recommended prior to the start of treatment, and treatment with abacavir should only be considered for HLA-B*5701-positive patients under exceptional circumstances. Further examples include clopidogrel (Plavix®), whose metabolism is affected by genetic polymorphism in the CYP2C19 gene. A boxed warning on the Plavix® product label suggests genotyping to identify poor metabolisers, with an indication that those patients should consider alternative treatment. Responsiveness to warfarin is affected by polymorphism in the VKORC1 and CYP2C9 genes, and different starting doses are recommended depending upon a patient’s VKORC1 and CYP2C9 genotype.
At least in the context of relabelling drugs, the FDA currently expects that if a diagnostic test is essential for the safe and effective use of a therapeutic product, there is a cleared/ approved diagnostic test available concurrent
with the drug label change. Tis may well also be the case for newly approved products. Terefore, pharmacogenomics information obtained during a clinical trial has the potential to result in patent opportunities for obligatory companion diagnostic assays and kits, whether they are exploited in-house or out-licensed to a third party. Moreover, it may be possible to obtain patents for new methods of treatment, including a patient screening step, and medical uses based upon a newly defined population of patients to be treated. Such patents are potentially of great value in providing effective market exclusivity, particularly if the drug is only approved for use in the specified populations.
It is also possible that the
stratification observations may lead to new compound screening methods and, potentially, identification of new chemical entities.
In the examples of abacavir, clopidogrel and warfarin, the pharmacogenomic information was only discovered post-marketing. With the growing facility for gathering and analysing ever greater volumes of data, it is more likely that correlations of this type will be picked up earlier in the clinical trials process, potentially
40 Life Sciences Intellectual Property Review 2011
www.worldipreview.com
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