Celebrate_coverTaken from our recently published report, Celebrating UK bioscience, the story of AstraZeneca’s newly approved first-in-class Lynparza (olaparib) for ovarian cancer showcases the critical role played by the UK bioscience sector in the development of cutting edge therapies. It also highlights the promise of personalised medicine.

Lynparza is one of a new generation of targeted medicines aimed at patients with specific genetic mutations that mean they’re most likely to benefit from treatment. The drug is approved for women suffering from ovarian cancer thanks to expertise and partnerships spanning the entire UK bioscience sector: from academic research excellence at University of Cambridge, through funding and support from cancer research charity Cancer Research UK (CRUK), biotech entrepreneurship and UK venture capital backing at KuDOS Pharmaceuticals Ltd., and the clinical development expertise and resources of UK drugs giant AstraZeneca.

Knocking out cancer’s repair mechanism

Lynparza’s approval in December 2014 for patients with advanced, pre-treated ovarian cancer offered a much-needed treatment option for many patients suffering from this relatively rare disease. Lynparza was shown in trials to prolong survival for six months or more among women with advanced, BRCA-mutated ovarian cancer.

The drug is a poly ADP-ribose polymerase (PARP) inhibitor, which kills cancer cells by knocking out their ability to repair damaged DNA. Cancer cells displaying mutations in the BRCA1 and BRCA2 genes are thought to be particularly vulnerable to this form of attack. Crucially, inhibiting PARP – an important DNA repair signalling molecule – doesn’t appear to affect healthy cells, unlike traditional treatments that directly attack cells, such as chemo- or radiotherapy.

Lynparza’s mechanism of action means it has potential across a wide range of tumour types whose cells have DNA repair deficiencies.

A PARP enzyme bound to a DNA double strand break. A PARP inhibitor kills cancer cells by knocking out their ability to repair damaged DNA.

A PARP enzyme bound to a DNA double strand break. A PARP inhibitor kills cancer cells by knocking out their ability to repair damaged DNA.

A team effort from across UK bioscience

Lynparza emerged from work in the 1990s by Professor Stephen Jackson and his team at the University of Cambridge. With research funding from CRUK (then known as Cancer Research Campaign), Professor Jackson’s group was looking at the role of various DNA repair proteins in cancer cells that help these cells survive. As the potential of such proteins as targets for drug therapy became clearer, Professor Jackson set up KuDOS Pharmaceuticals Ltd., initially within his Cambridge labs, in 1997. CRUK’s technology transfer arm, known today as Cancer Research Technology (CRT), provided seed funding. Two years later, the company attracted a combined £5 million from Advent Venture Partners, Schroder Ventures Life Sciences, and 3i Group. The start-up more than trebled its head-count and moved into new laboratories at the Cambridge Science Park. KuDOS continued to collaborate with Professor Jackson at Cambridge University.

In 2005, KU59436 – the precursor to olaparib – was only in Phase I trials, a relatively early phase of development. But AstraZeneca was engaged in a flurry of pipeline-enhancing dealmaking. It liked KuDOS’ DNA repair platform and the early clinical candidate. In December that year, AstraZeneca paid over £120 million to buy the company outright.

The collaboration with CRT continued and has further evolved since. In 2010, AstraZeneca and CRT allied to discover drugs targeting cancer metabolism – how cancer cells use energy to grow – and expanded this alliance in 2013 for a further two years. Indeed, Professor Jackson pointed out on the day of Lynparza’s approval in 2014 that the achievement “…shows how, by collaborating with a partner such as AstraZeneca, basic academic research, such as that carried out by the research team at the University of Cambridge, can lead to major medical developments.”

AstraZeneca has further deepened its partnership with UK academic expertise, setting up a joint research facility with the MRC, the AstraZeneca MRC UK Centre for Lead Discovery, in Cambridge. That Centre is working with CRUK to screen for new cancer medicines in a five-year collaboration that provides CRUK scientists with access to over two million compounds from AstraZeneca libraries.

Another tool against cancer, multiple new research avenues

Scientists’ understanding of the potential of PARP inhibitors in treating cancer has much further to go. There may be several other mutations, as yet unidentified, that mark out patients likely to benefit most from this type of treatment. The combination treatment options are also growing exponentially as new therapies are approved.

There are further challenges however, even after approval, to ensure that Lynparza and related targeted treatments are accessible to those who need them. In June 2015 NICE opened its consultation on draft guidance on olaparib for ovarian, fallopian tube and peritoneal cancer and at the time of publication it has not recommended funding the drug on the NHS. Professor Peter Johnson, Cancer Research UK’s chief clinician, commented saying, “NICE’s provisional decision is hard to understand. This is a great example of a personalised medicine which offers a new treatment for a type of cancer where we have made little progress in the last decade and where there is a clear need for different approaches. The NHS can’t afford to ignore important innovations like this”.

Like to find out more? The full version of the Lynparza story, along with five other case studies, can be found in our report,“Celebrating UK bioscience: unravelling the stories behind UK bioscience success”.