Revolutions in immunological therapies are showing very promising clinical results in the fight against cancer, challenging pharmaceutical access and funding systems that have underpinned Australia’s internationally envied healthcare system.
Using the body’s immune system to directly attack cancers, the early success of so called “wonder drugs”, has spurred a massive global research pipeline, with the first batch of immuno drugs now winning clearance in Australia and in the US.
These drugs have raised the very real prospect of humanity finally being able to prevent cancer for all but the most elderly. This has excited both patients and the oncology community around the world. But because the drugs are typically very expensive and often directed at a relatively small population of rare cancer patients, they raise major issues for health policy makers and regulators.
At a forum convened by The Mandarin in Canberra recently, industry experts discussed the complex issues that need to be considered as a large pipeline of immuno drugs is expected to become potentially available to patients. The forum heard from a panel, which included the Chief Medical Officer for Merck Research Laboratories, Dr Roy Baynes, Managing Partner of Deloitte Canberra, Lynne Pezzullo, the eminent Australian oncologist, Professor Ian Olver and Richard Vines, the CEO of Rare Cancers Australia.
Until recently chemotherapy and radiotherapy have been the principle modes of attacking cancer, broadly attacking the cancer directly with toxins. Australia has been a leader in this approach and has one of the best cancer survival rates in the world.
But while death rates as a proportion of population have fallen by about a quarter over the last 30 years, around 130 Australians a day still die from cancer, with an average of 367 people a day diagnosed with a new case of cancer. Cancer is also Australia’s leading cause of loss of healthy life years.
It is cancer’s propensity to hit people in their healthy years which has fuelled massive research into cancer cures and the emergence of immuno drugs as an exciting area of breakthrough innovation.
This immuno breakthrough has spurred an extraordinary research response, with an estimate that among the ‘big six’ pharma companies there were around 1800 different trials around the world.
Several of these are now entering later generation phases. Professor Ian Frazer’s work through the University of Queensland on cervical cancer and the HIP virus is an example of a mature research environment. Melanoma is also an area where Australia has developed a deep research base.
The forum heard that this new class of immuno drugs is showing very promising remission rates in clinical trials in certain patient groups, with reports of some patients living a completely normal lifestyle though their treatment program. The early success has made the knowledge base develop very quickly, with numerous reports of significant remission rates in trials.
But it was noted there remains a significant percentage of patients that see little or no benefit, as well as reports of relatively severe side effects in some patients.
Clinically, it was explained, researchers are still trying to better understand the mechanisms of primary and secondary resistance to the drugs and what combinations were most effective.
The treatment approval and reimbursement system that Australia has successfully developed is designed around large scale clinical trials — and funding drugs that will give the greatest benefit to the greatest number.
Rare cancers are by definition limited to small patient groups, which means drugs have difficulty getting therapeutic approval. The high cost of the research means immuno drugs are expensive and because the benefit group is limited, reimbursement through the Pharmaceutical Benefit Scheme is problematic.
The forum heard immuno drugs work at the molecular level which means the traditional characterisation by body type was not relevant. Indeed to the extent reimbursement was based on body type ( eg lung cancer) immuno drugs were not able to fit in traditional funding models.
This prompted a discussion about the use of biomarkers, to more precisely focus the provision of immuno drugs to patients most likely to respond. It was explained that biomarkers effectively tell clinicians whether the tumour has the target that a particular therapy is designed to counter, meaning the drugs can be much more precisely focussed. Biomarkers are naturally occuring signifiers of a biological process and can be used to track certain bodily behaviours.
The use of biomarkers opens the possibility of much more precision in the use of immuno drugs, ensuring a far higher response rate and a lower cost. Targeting the actual bio marker that is relevant to the success of the immuno therapy also potentially provides a more efficient approach for policymakers wanting to fund based on efficacy.
Given the molecular nature of the therapies it was also suggested it was possible to cluster therapies around particular molecular types and deal with the therapies as a pack.
This raises the issue of the use of data to better track patient responses. Australia is beginning to roll out an opt out eHealth regime, but it was argued a real focus on digitising patient records and standardising data collections is needed. With some rare cancers unlikely ever to have a mass of patients to test drugs, it will be critical to capture data across a wide range of smaller trials.
News of the positive clinical results from the use of immuno drugs has sparked substantial patient response, especially in the area of rare cancers. Traditionally these have been difficult to treat and the opportunity to access possible life saving drugs has seen patients clamour to be part of trials.
The possibility of cures for previously untreatable diseases, has cereated a push for access rules to be adjusted to accommodate the smaller trial groups inevitably associated with rare cancers. Current funding rules make it problematic for individual hospitals to fund access.
This leaves patients — who don’t have the savings to pay for the drugs — in the invidious position of being denied drugs that could be highly responsive to their rare cancer. These cases attract media and political attention raising pressure on regulators to accelerate access to the drugs.
Work done by Deloitte Access Economics on patient attitudes to these drugs confirmed many patients were struggling to find accurate information about the drugs. The rapidly developing pipeline of trials has also challenged clinicians to stay on top of the research base.
The Mandarin’s forum was told patients described a lack of information available to them, and navigating a system where they felt they were “wandering around in the dark.”
Patients are not aware of what therapies are available to them or how affordable these are; and they identified all sorts of issues through both the registration process and reimbursement processes of medicines. Given the very different response rates in patients’ groups, and the significant side effects some patients have endured, this was called-out as an area of pressing work.
It was explained that from the research and pharma perspective, working within the regulations was important. Because the drugs look so effective, there is a strong desire to do the trial of one all the time.
If a doctor has a patient with a cancer that’s not responding, the clinician will naturally ask what would happen with an immunotherapy drug. And while this it is incredibly important to that person, it’s also important to collect the data and actually advance the field so the overall benefit risk in rare cancers can be understood.
Regulators around the world are considering how to respond to the particular access issues raised by immuno drugs and rare cancers. In the US for example, regulators have been quite receptive to alternative trial approaches to looking at the benefit and risk issues through a basket of trials rather than one large scale trial.
This pan tumor approach is essentially agnostic to the body part or where the primary cancer emanates from, effectively delinking access and reimbursement. Health Minister Greg Hunt has noted this “democratisation of cancer” approach as a possible area of development.
It was observed cancer drugs typically take around 590 days to get approval, compared with 200 days on average for other drugs. With suggestions that there could be quadruple the number of immuno and other similar applications coming down the pipeline over the next year there is an urgency to find an appropriate access regime.
Finding the appropriate balance between public access and ensuring investment in the innovation now fuelling the large research pipeline remains a critical issue. The US marketplace funds a massive amount of pharma research and there has been a long held view that US patients should not be bearing all the costs of getting these and other innovative drugs to market.
The design of local access and testing regimes are also important for determining the location of trials and the associated investment. Australia has a proud record in cancer treatment and has been a relative leader in the immuno space. Our research and clinical development community stands to be a major beneficiary if the access and reimbursement regimes are attractive to international pharma players and investors.
The pharma sector has been the focus of a major federal government industry growth scheme known as MTP Connect. Aligning clinical and patient needs with the important regulatory and policy requirements is part of this on going effort to open Australia to the large opportunity in he area of molecular research.
In this regard it was noted that the usual assumption of declining long term prices might not be true, given the relatively bespoke nature of the treatment. This was seen as an opportunity for a lot more scope to do innovative access arrangements. This could includes managed entry schemes, through risk sharing agreements and a shift to more innovative financing and funding arrangements.
