About...
David Cavalla
Numedicus Limited (Cambridge, England) was established in 2008 to provide collaborative services to companies seeking expert advice in the area novel uses for existing drugs, or 'drug repurposing'.
Its founder David Cavalla has 23 years experience in various senior scientific and commercial roles within the pharmaceutical industry. He is currently involved with a number of biotech companies at Board level, principally Switch Pharma Group plc. He is also a member of the Scientific Advisory Board of Peakdale Molecular Ltd. Previously he was founder and CEO of Arachnova Ltd, a company focused on therapeutic switching, from which he exited as a result of a trade sale; previous affiliations included Glaxo Group Research Ltd and Napp Research Centre, where he was Head of Biosciences.
He was one of the first advocates of the virtual strategy of pharmaceutical R&D, and more recently of drug repurposing, and frequently contributes articles on pharmaceutical strategy. He is on the editorial board of Drug Discovery Today. Formerly he was Chairman of the Society for Medicines Research. He obtained a first degree and PhD at Cambridge University and spent two years as a visiting Fellow at the NIMH, Washington, DC. He is author/inventor of over 70 published papers and patents.
Numedicus Limited
Finding a new indication for an existing drug (or a developmental one) has been the basis for a good number of medicines over decades, from Viagra™ to thalidomide (Thalidomid), often by serendipity. Recently it been advocated as a strategic means of enhancing R&D efficiency, through its combined allure of reduced risk of failure, time and cost of new product entry.
Indeed, the setting of known active pharmaceuticals in new presentations and for new uses is becoming an increasingly common approach to new medicines. Art Pappas of Pappas Ventures noted that 43% of the new drugs approved by the FDA in fiscal year 2007 were through the 505(b)(2) rather than the more complex NDA route.
The traditional approach to new medicines involved a dominant concentration on the active pharmaceutical ingredient, to be taken in a conventional oral presentation and for a therapeutic indication that was set early on in the discovery process. However, new formulation technology opened a second dimension in medicinal discovery, increasing the opportunity to tailor the product for patient preference and convenience, as well as to provide a differentiated and commercially protected offering. Thus, there are many examples in which the same product is available in different presentations, with the later generations deploying formulation technology for various advantages.
It is now clear that new biological discoveries open up new vistas for old medicines, often uses that were not appreciated at the time of the original discovery. Like new formulations, these uses offer both differentiated and commercially-protectable avenues for innovation. The advantages of this approach, often called drug reprofiling or therapeutic switching, have been documented in numerous published articles.
Gleevec™ (or Glivec™ outside the US) (imatinib) is a good example of a drug that has become appreciated for its wider uses some time after appearing on the market for an orphan disease. Originally it was approved for chronic myelogenous leukaemia (CML), a rare but devastating condition that begins in the often asymptomatic chronic phase, and over the course of several years progresses through an accelerated phase and ultimately to a blast crisis, by which time it is associated with a very high mortality rate. From diagnosis, the median survival period is just over five years.
Gleevec™ is now also approved for nine other indications including gastrointestinal stromal tumour (GIST); but these are still relatively rare conditions. A recent report that the same drug has effects in an animal model of type I diabetes could take the drug into another dimension. Or could it?
Imatinib actually affects the activity of three kinase enzymes. The first is the kinase enzyme for which it was screened (PDGF-R); the second is implicated in CML (bcr-abl); and the third is involved in the secondary use in GIST for which imatinib is now also approved (c-kit). This is somewhat ironic since enzymic selectivity was at the heart of the discovery process.