Bucking the trend

THE FOUNDATION for Research Science and Technology released its new strategy for a ‘stable research funding environment’ in 2006, focusing long-term support on Crown Research Institutes and the primary sector. This seemed to be on the quite reasonable basis that this sector accounts for close to 65% of total export earnings and primary industry still contributes about 10% of our GDP; even small percentage gains in productivity will translate into significant returns. But the flip side of the coin is, of course, that despite our primary industry economic backbone, which has a 150-year history of genetically enhancing crops and animals, New Zealand continues to slip down the OECD rankings whilst we yearn to emulate the economic growth of countries such as Ireland and Denmark.

When it comes to surfing our ‘knowledge wave’ or capitalising on our research-driven economic transformation, we can’t seem to quite make the grade. Or can we? Take a closer look at an interesting biotechnology trend that has evolved in Auckland with six pharmaceutical companies spinning out of the University of Auckland since 1994. It is generally considered internationally that 90–95% of pharmaceutical startups will fail, predominantly in the preclinical phase, yet drugs from four of those Auckland spinouts are currently in clinical trials — one at phase III — with a fifth company to shortly follow suit. Even ignoring the fact these New Zealand companies have shattered the worldwide trend to failure, and sticking to the worldwide law of averages from here on in, at least one, if not two of those companies should see products into significant markets (20% of drugs entering phase II get to market, with 30% going to phase III ultimately reaching market).

I’m well aware it is politically correct to display scepticism about every drug candidate that comes into view, and there are still many pitfalls and regulatory hurdles to be met, but perhaps more telling than the cold statistics is that five of those six University of Auckland spinouts have data showing their products work in humans. Neuren announced in early May it is to take its lead product, Glypromate, into phase III trials with the US Army’s Walter Reed Institute; ProActa raised a further US$35 million in February and is moving PR-104 into the next phase of trials, establishing a second trial site in Auckland; Living Cell Technologies announced in late March that it has a patient still benefiting from its encased cell technology for diabetic patients ten years after treatment; Protemix raised a further US$14.5 million in April and is taking PX811019 into phase II with three other products in preclinical development; and CoDa Therapeutics has two compassionate-use cases in which eyes of patients have been saved following treatment with its lead tissue repair product, Nexagon. All five companies still need to go about planning their clinical development and regulatory strategy with an eye towards maximising success whilst avoiding the safety and efficacy pitfalls, but all of them know they have a drug or therapy that could bring huge benefits to millions of patients.

Ted Greene wrote recently to fellow board members of CoDa Therapeutics, “the spectacular drug breakthroughs have been accomplished by people who firmly believed in the ultimate efficacy of their ideas”. He gave as an example Amylin Pharmaceutical’s lead product, asking whether Amylin would have survived 20 years of battling the sceptics had those involved not known in their hearts that Symlin would work? Amylin, whose scientific founder was Auckland University’s Professor Garth Cooper, had a market capitalisation of US$5.47 billion at the time of writing. The founders of ProActa in the New Zealand Cancer Society Research Centre laboratories at the University of Auckland have also developed other drugs in clinical trials, with their DMXAA (AS1404) taken to phase III in 2006 by Antisoma in the UK. In April this year, Antisoma completed a deal for this drug with Novartis worth at up to US$890 million plus royalties.

It is interesting, then, that as a nation we will invest $885 million into our national air carrier so it can compete in one of the world’s most difficult markets, notorious for bankruptcies and Chapter 11 incursions, yet our government research funds, investors and business communities have been timid in backing New Zealand biopharmaceutical developments. Our beliefs risk becoming our self-fulfilling prophecies. There is good news, though. The number of New Zealand scientists and entrepreneurs flying overseas to conduct collaborations and clinical trials, meet with regulatory authorities such as the US FDA, or attend board meetings for their now overseas-based companies, at least ensures our stake in Air New Zealand must be paying some dividend. And whilst anecdotal results don’t carry any weight with the FDA or investors, the people working for those five companies spun out from the University of Auckland go to bed every night knowing they have a drug or treatment that works. And the extraordinary track record for New Zealand pharmaceutical research and discovery continues to buck international expectations and trends.

Professor Colin Green is a founding scientist and director of CoDa Therapeutics (NZ) and CoDa Therapeutics (San Diego). He holds the W&B Hadden Chair of Ophthalmology and Translational Vision Research in the Faculty of Medical and Health Sciences at the University of Auckland