Tiny doses for early trials
microdosing service aimed at reducing failure rates of candidate
drugs at Phase I.
Pharmaceutical Profiles and fellow UK company Xceleron have set up a partnership to offer a commercial human microdosing service aimed at reducing failure rates of candidate drugs at Phase I .
As many as one in three drugs fail in Phase I clinical testing despite extensive preclinical screening of potential clinical candidates with a wide variety of in silico, in vitro, ex vivo and animal models. A high proportion of subsequent product failures can also be attributed to unsuitable pharmacokinetic or inappropriate absorption, distribution, metabolism and excretion (ADME) properties, manifesting themselves as equivocal efficacy or safety issues in man.
"The best model for man, is man," commented Prof Ian Wilding, Pharmaceutical Profiles' executive chairman. The two companies are hoping to use Xceleron's microdosing technology - in which only a very tiny amount of active substance is administered - to start proof-of-concept studies early, and save both time and money by advancing only those candidates that are more likely to succeed.
Xceleron's AMS is the most precise measuring device ever invented, up to 100,000 times more sensitive than liquid chromatography-mass spectrometry (LC-MS) and 1,000,000 times more sensitive than liquid scintillation counting (LSC),and can produce the microdoses needed for this type of clinical evaluation. Pharmaceutical Profiles will provide the expertise in Phase I/IIa trial design and operation.
"There is a natural fit between our companies and the type of services we provide," said Prof Colin Garner, Xceleron's CEO.
In microdosing studies, one or more drug candidates is administered to humans at sub-pharmacological (microgram) levels to obtain early PK and ADME data in order to select the candidate with the optimal PK characteristics. The approach has been endorsed by the European Medicines Evaluation Agency (EMEA), which has determined that a microdose is 100 times below the level calculated to yield a pharmacological effect, or 100 micrograms, whichever is the lower.
According to prof Garner, "microdosing will be the standard procedure for 'first-in-man' studies for drug development in the future; the drivers for microdosing studies will come from the regulatory authorities and the general public since microdose studies are safer and reduce the use of animals prior to human testing."
