HuTrial - human surrogates for clinical trials becomes a reality

In early June, Crown Bioscience unveiled its new human surrogate trial platform, HuTrial, which functions as a low-cost substitute for a phase-II trial. Through conducting a HuTrial, researchers could be able to predict the efficacy of a prospective candidate early in the drug development process, helping to reduce the failure rate at the later stages of clinical trials. Abby Miller spoke to Jean-Pierre Wery, president of Crown Bioscience, to find out more. It's a regrettably common story: a drug candidate shows great potential, only to fall at the final hurdle. After investing millions of dollars into its development, a pharma company is left with nothing to show for their efforts. Nothing, that is, except the hefty price tag associated with late-stage drug attrition.

HuTrials are conducted using Crown's HuPrime patient-derived xenographs (PDX), which involve transplanting primary tumour cells directly from a patient into an immunodeficient mouse. As the new tumour develops, it retains all the key characteristics of the original. This means the surrogate truly represents the patient, and accurately determines how their cancer is likely to behave. While patient-derived xenographs in themselves are nothing new, this is the first time the technique has been used to simulate clinical trials.

FIGURE: HuPrime patient-derived xenographs (PDX) involve transplanting primary tumour cells directly from a patient into an immunodeficient mouse.

Targeting patients

Especially within oncology, phase-II clinical trials are notorious for their failure rate - an exciting preclinical candidate does not always translate into a successful drug. This is largely due to the fact that cancer is such a heterogeneous disease. Even if you take two lung cancer patients, nominally suffering the same 'type' of cancer, the underlying biology may be entirely different.

This means that any given drug candidate is unlikely to work well across the board. You need to pinpoint exactly which patient group will benefit, if the candidate is ever to make it past the preclinical stage.

HuTrials provides an intriguing potential solution. In essence, Crown enrols not patients but tumour models into a clinical trial. This gives a great deal of flexibility to test out treatments, discerning the different effects of each drug on any given tumour type.

Cutting time and costs

Technically, the requirements are similar to those in a human trial: you need an adequate number of 'patients', and sufficient diversity in your tumour models. Here, though, there is an additional important factor, which is keeping the tumours alive. Typically mouse tumours would be cryopreserved until needed, but when conducting HuTrials the timelines are too short to make that a viable option. Crown therefore keeps a ready stock of mice available for trial enrolment.

"If you want a HuTrial with 50 models, and you have go back and regenerate all these models from frozen tumours, that's very cumbersome," says Wery. "Most of your customers will say you're going to get clinical trial information too late. So unlike many companies, Crown keeps a lot of models alive whether or not the customer's going to use them."

If speed is one key advantage, the other is surely cost. While a typical phase-II or III trial costs millions of dollars, a pharma company can undertake a HuTrial at a fraction of the price. It's a worthwhile investment, ensuring that only the most effective candidates make it through to the next phase of testing.

Bridging the divide

The idea, of this technique, is to accelerate the passage of promising drugs to the clinic - ensuring that clients do not waste resources on ineffective treatments, while at the same time helping pinpoint drugs that could benefit a specific population. HuTrials can enable companies to go from an interesting pre-clinical drug candidate to clinical success."

Posted By:-

Biotechnology Department