CONTRACT RESEARCH & TOXICOLOGY
your programme ,” Stallons said . In one workshop the FDA carried out in 2015 , one reviewer was unaware of any precedent for a negative outcome in a human drug programme of an AE carried out in a veterinary trial .
Thus , taking everything in context , Stallons conclude that “ there is a realistic marginal risk to the human drug programme that should be weighed against the actual significant benefit for the appropriate disease model .” Other considerations , depending on the specific trial , may include :
• Dogs and cats are used much less frequently in non-clinical pharmacokinetic and toxicity studies now so less data may be available to justify safety , dose and route administration when using them
• Patient numbers are likely to be small , depending on the disease
• Species-specific reagents and test article requirements and , depending on the disease state , finding sufficient sites with the required expertise can all be issues
• There may be competing trials for rare diseases
Outlook
The key take-home message from both webinar speakers was that we have the opportunity to move the non-clinical safety assessment paradigm and thereby address the very high rate of clinical trial failure . The One Health concept is real and clinical trials in companion articles may provide supportive safety and efficacy for certain diseases in humans .
In the US , the National Cancer Institute ’ s Comparative Oncology Programme has a multi-centre collaborative network , including 20 academic centres running clinical oncology trials , and there is a virtual pharmacodyamics ( PD ) core facility offering fee-for-service assays . And most importantly , there are several case examples where translational research has successfully supported human clinical trials . ●
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Stallons - Collecting safety points helps speed drugs to the clinic
Case study on cancer
Dr Elizabeth Neyens , a certified toxicologist , toxicological pathologist and owner of Flanders ToxPath Consulting , shared two case studies during the ACT webinar where companion animal models have shown promise in the development of human drugs . One related to immunemediated ocular diseases , the other to cancer .
Although advanced treatments like radiotherapy , chemotherapy and even immunotherapeutics are now available to domestic animals too , cancer is still very common among them , Neyens noted . More than half of dogs develop cancer if they reach the age of ten . Humans and domestic animals have many cancers in common , such as lymphomas , osteosarcomas and melanomas .
Developing cancer drugs in the clinical stage often requires animal models that express tumours , normally in mice without xenografts . These can present genomic instability and tumour heterogenicity , making the translational process difficult to achieve .
“ When studying a companion animal carrying these spontaneous diseases , there is a synergy between the host and the tumour environment ,” said Neyens . “ Here , we are not dealing with the genetically modified laboratory animals . Their immune systems have not been modified and their immunity is intact .”
There are several cancer therapeutics where the companion animal disease can support drug development in humans . This depends on the type of cancer but the two species share such features as background genetics , histological appearance and therapeutic responses .
One canine model has been developed for malignant melanomas via the administration of interleukin ( IL ) -12 . IL-12 comes with a high risk of systemic toxicity that has caused some past trials to fail . However , canine and human IL-12 have strong similarities and the melanomas that they develop are also similar .
To date , the PK and PD toxicity and efficacy of IL-12 have been characterised in canine clinical trials . The results suggest that it could be safely administered subcutaneously to patients with malignant melanomas while maintaining full systemic , immunological and clinical activity . The findings in these trials guided the sponsor to move forward with Phase I clinical trials in humans .
28 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981