Personalised medicine

The investment that has been put into personalised medicine is starting to pay off - the tailored diagnosis, prognosis, treatment and prevention of disease in an individual is beginning to be applied, as David Randerson intends to explain at the conference.

Defining treatment through an individuals’ genetic and phenotypic information promises better management of diseases that will bring benefits to the economy, society and people’s quality of life.

According to David Randerson, Chief Executive Officer and Managing Director of TransBio and the Cooperative Research Centre (CRC) for Biomarker Translation, one of the big drivers of personalised medicine is the cost of healthcare delivery.

“Personalised medicine is important from an economics point of view because the cost of treating patients is becoming prohibitively expensive,” said Randerson, who will open the personalised medicine session at the conference.

“For example, there is a new cystic fibrosis drug on the market that costs $300,000 a year,” he said of the medication Kalydeco, which was recently approved for use in Australia.

Patients with cystic fibrosis who have the G551D mutation are eligible for this treatment.

Other specific cancer drugs, such as the prostate cancer immunotherapy Provenge, costs up to $100,000 for a course of treatment, and ongoing biological treatments for rheumatoid arthritis cost between $13,000 and $30,000 for a course.

Because new drugs coming onto the market are getting more and more expensive, identifying whether a patient will respond or fail or develop adverse effects is key to appropriately directing national health and insurance costs.

Giving the same treatment to every patient with a particular disease is not economical because many of these patients will not respond to the treatment. It also increases the potential of serious side effects developing.

“As drugs become more targeted the potential to develop serious side effects become greater,” Randerson explained. “So if you can identify patients who will respond to a particular treatment, you are treating them with the knowledge that the drug will be effective.”

Preventative medicine

Personalised medicine is also important from a preventative perspective, which links to the expense of healthcare.

Biomarkers, genetic markers or proteomics can be used to identify and monitor people who are predisposed to getting a particular disease. They can then be encouraged to modify their lifestyle or be treated before they progress into that condition.

“It may be arthritis or Alzheimer’s disease, then you can pre-empt that disease, treat people and treat them cost effectively,” Randerson said. “Whereas treating patients who are not going to respond to the treatment is a waste of time and money.”

According to Randerson, Australia is particularly good at this preventative approach, as is Europe.

One of the early targeted therapies identified was the monoclonal antibody Herceptin. A relatively large subgroup (25%) of patients with breast cancer - those with human epidermal growth factor receptor HER2-positive breast cancer - responded to the targeted treatment.

“It may be that 25% of breast cancer patients are amenable to herceptin but, in reality, you go through and select those patients as part of your clinical trial,” explained Randerson. “We are doing this right now with some of the work at the CRC. We look at where a particular drug will be effective, which patients are most amenable to the drug, then we identify those patients by a test, using a biomarker for example, and then go into a trial. Otherwise we are not going to be able to get statistical significance.”

Companion diagnostics

Coupling a diagnostic test with a drug is beneficial from a number of perspectives. From a company’s perspective, aligning a diagnostic test with a particular therapy may give them greater protection from a patent point of view.

“It enables companies to verify that their drugs are effective in a particular subset of patients,” said Randerson. “This gives them a stronger market presence.”

From an individual’s perspective, it enables clinicians to determine which drug is going to work best for a person with minimal side effects.

It also prevents a potentially good drug from being rejected because it has no or minimal effect in the whole patient population. Randerson believes that many potential new drugs that may have worked in 1, 5 or 20 per cent of a patient population have been lost over the years because their effects did not appear in the data.

The FDA has already approved at least four drugs, and Europe has approved 11, that require a specific concomitant diagnostic test to be conducted. The test identifies whether the patient is part of a particular subset of that disease and is therefore likely to respond to the treatment.

Randerson predicts that this type of testing will become more and more common as personalised medicine gains ground in the future.

“It is a much more targeted groups of patients that these therapies are being developed for, and this is changing the way things are done,” he said.

The end of a term

One project currently underway within the CRC for Biomarker Translation involves a program for developing specific markers to detect T helper cells - Th1 and Th17 cells.

Th1 and Th17 cells are involved in the inflammatory process in rheumatoid arthritis and the work, conducted at the Burnett Institute in Melbourne, has identified a number of specific markers for these cells.

Randerson predicts there may be a therapeutic interest in these cells in the future but, with only a year remaining of its seven-year term, the CRC does not have time to pursue this pathway. Instead the focus is on developing a guiding tool or diagnostic for treatment with a focus on rheumatoid arthritis.

The treatments available for patients with rheumatoid arthritis all have a significant rate of failure.

A specific population of Th17 cells is present in some patients who respond to a specific therapy. By monitoring the Th17 cells, or specific subsets of T cells, in these patients, the researchers hope to be able to predict those patients who will respond to a particular treatment.

“We look in the synovial fluid taken from patient’s joints and can demonstrate there’s a subset of Th17s which are identifiable by a specific marker,” said Randerson. “These can be used to guide therapy and will produce better outcomes for patients with fewer side effects and less waste.”

Randerson hopes that over the next 12 months the team will be collaborating with a major drug company to finalise some of the work that has come out of the CRC before its term ends in July 2014.

“We’ve identified several hundred biomarkers and then developed or used commercially available monoclonal antibodies to validate those biomarkers,” Randerson reflected.

Randerson said the CRC has narrowed its work down five or six projects and is hopeful that over the next 12 months the projects will attract licences or investment.

David Randerson is Chief Executive and Director at TransBio Ltd and the Cooperative Research Centre for Biomarker Translation and Managing Director at Acuity Technology Management. He studied his undergraduate at Monash University and completed a PhD in Biomedical Engineering at UNSW. He has worked as a research scientist in academia and industry. His current focus is on providing advice on R&D and commercialisation in the healthcare and biotechnology sector.

Image credit ©stock.xchng/profile/matchstick