Product Rescue: Case Histories

Compound A

is a novel anticancer agent. The compound had been shown to cause hepatic tumours in mice.
During the development of Compound A the sponsor and CXR Biosciences built up an interactive relationship whereby CXR provided advice and experimental data at all stages of the process.
CXR designed assays to demonstrate that the mechanism of tumourigenicity was not relevant to man. By establishing this relationship the sponsor was able to characterise the bioavailability and metabolism of the compound, avoid problems which could have arisen in clinical trials, and understand interindividual variability in pharmacokinetics and response.
CXR enabled the product registration to be maintained.

Compound B

is a potential anticancer agent which had previously been studied using traditional biochemical approaches. These had suggested that it might act via one of the peroxisome proliferator activated family of nuclear receptors (PPARs).
CXR Biosciences undertook a series of studies to elucidate the mechanism of action of Compound B, including target validation, characterisation of novel signalling pathways and the identification of pharmacodynamic markers for use in clinical trials.
As a result of these studies, Compound B is now poised to enter Phase I clinical trials.

Compound C

has low mammalian toxicity and is non-genotoxic in conventional assays for mutagenicity and clastogenicity. However, when administered to Fischer 344 rats in a two year bioassay Compound C induced liver tumours and thyroid follicular cell neoplasms in male and female rats and renal adenocarcinomas in male rats only.
Significant human exposure to Compound C occurs and the discovery of its carcinogenicity led to concerns over potential human health problems.
CXR Biosciences initiated research aimed at understanding the mechanism of carcinogenicity in rats, in order to evaluate the potential hazard of exposure of humans to Compound C.
Based on the studies carried out by CXR Biosciences the regulators accepted CXR's data and arguments and this compound was not classified as a human carcinogen.

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