Highlights of a recent panel debate moderated by Christian K Schneider, head of Biopharma Excellence, reviewing emerging approaches to clinical data collection where patient populations are small.
Biopharma Excellence recently hosted a panel discussion featuring experts in biotech and the evolving regulatory environment to discuss the challenge of achieving statistical significance with novel and highly targeted therapies. Daniel O’Connor of the UK’s MHRA noted that the challenge of achieving statistical significance when target populations are tiny is nothing new, but conceded that randomised trials aren’t always viable – especially with very rare conditions. He urged drug developers to seek scientific advice before finding workarounds.
When Trial Data is Lacking
The panel considered the potential for supplementary data sets – such as pharmacodynamic read-outs, histological evidence and historical controls – in enabling regulators to reach robust decisions. Nick Sireau, of AKU Society, talked about his early experiences of trying to get new drugs approved for Alkaptonuria (AKU); his two sons both suffer from the ultra-rare disease. His organisation relies heavily on grant funding and donations, with access to funds often difficult. It doesn’t help that the authorities’ requirements for clinical evidence have been quite restrictive up to now. Fifteen years ago, 40 patients were recruited to an AKU drug trial that lasted three years and focused on a single endpoint (hip rotation), Nick explained. “The trouble is, that AKU affects patients very differently,” he noted. “So to just look at 40 patients with a single endpoint proved futile.” Although patients were reporting that they could walk further, that their pain had reduced, that they were feeling better since joining the trial, the study itself failed.
This led AKU Society to form a consortium of linked organisations across Europe, and a composite end point – a proposition which by then was well received in the EU. “That changed everything,” he said.
Daniel argued that the industry is now witnessing an evolution in regulatory thinking, resulting in a much more proportionate approach with regard to looking at the disease condition based on how much is already known: “not just thinking about either a randomised study or a single-arm study.”
Oncology’s use of basket studies has helped shine a light on what’s possible, he added. “But there’s also a lot of work now looking at shared molecular entities in rare diseases – something the International Rare Diseases Research Consortium (IRDiRC) is moving on quite quickly now.” The toolbox to get to the data now needed is visibly expanding, he said.