New US sponsor steps in after unacceptable toxicity found in trials with some patients.

A promising lung cancer drug born of Daffodil Day funding has been rescued by a new American sponsor after a potentially disastrous finding of "unacceptable toxicity" in some patients.

Called TH-4000, the drug was invented by Dr Adam Patterson and Dr Jeff Smaill of the Auckland Cancer Society Research Centre and the Maurice Wilkins Centre at Auckland University. It becomes active only in the hypoxic parts of tumours, the zones without oxygen.

In development for a decade, the drug previously known as PR610 was first commercialised by the university in a deal with companies in Japan and the United States.

They put it through human trials to find the maximum tolerable dosage, the second of which is reported on a US Government register of trials as having been "prematurely discontinued due to unacceptable toxicity".


Dr Smaill said the joint sponsors pulled out last year because they felt the maximum tolerable dose wasn't sufficient for the types of cancer they hoped to target in further trials.

However a new sponsor, US company Threshold Pharmaceuticals, soon picked up TH-4000. It had been a roller-coaster ride, but the drug was now with the world's leading biotechnology company for the development of drugs that worked through hypoxia.

Threshold is planning two trials at the lower dosage in patients with a particular genetic mutation in cancer cells - one for those with non-small-cell lung cancer, the other for people with head and neck tumours.

Lung cancer is New Zealand's leading cause of cancer death. Each year around 2000 New Zealanders are diagnosed with lung cancer and the disease kills more than 1600. It is estimated that around 80 per cent of cases are the non-small-cell types.

TH-4000 is in the group of drugs that target human epidermal growth factor receptors (EGFRs) which are overactive or mutated in many cancers.

Today at a cancer research meeting in the US, the two Auckland scientists will present data from the lower-dosage trial, in which patients with various kinds of cancer received a one-hour weekly infusion of the drug. The most common adverse side effects included rash, vomiting and an electrical change in the heart.

Threshold has said the findings support its plans for trials of the drug's efficacy in patients whose tumours mean they are not suitable for conventional EGFR therapy.

Cancer Society Auckland division chief executive John Loof said it was great to see TH-4000 - early development of which would have been funded in part by the society's annual Daffodil Day appeals - had been given a second chance.

The results seemed encouraging, he said, but the drug still had a long way to go through the trials process.