It was HIV activists of the 1980s who first demonstrated how patient power can be used to shape and move forward research and influence regulator’s attitudes, as David Haerry, Co-Chair of the EMA’s Patient and Consumer Working Party
described. Amongst other successes were agreements on expanded access, the use of surrogate endpoints, conditional approvals and the testing of two products in a single trial.
But “while a lot went well” with the HIV agenda, the same cannot be said for securing access to breakthrough new medicines for Hepatitis C infection. This is despite the fact that these are massively more effective than standard interferon treatment. The process of securing reimbursement is “very bumpy”, even in rich countries such as his native Switzerland, Haerry said.
The problem is that Europe’s many HTA bodies are coming to different conclusions about the cost effectiveness of these products. “I can’t understand the discrepancies,” said Haerry. “If people got the drugs they would be cured.”
The route to navigating this impasse is to include HTA bodies early on in development, to get medicines to patients sooner and assess if they are cost effective once they are on the market, Haerry suggested. More broadly, there is need for a harmonised HTA methodology across Europe.
While there is an understandable pressure to get advanced therapies to patients as quickly as possible, there is a risk of going too fast and neglecting fundamental research, said Pieter Doevendans, Chief of Cardiology at the Utrecht Medical Centre, in an overview of attempts to develop stem-cell based therapies for restoring heart function following myocardial infarction. Doevendans was speaking on behalf of the European Society of Cardiology.
There was a disparate collection of preliminary evidence that administering a patient’s own bone marrow-derived stem cell into the heart soon after a heart attack was beneficial. However, a randomised controlled Dutch trial HEBE, in which Doevendans was involved, showed that although there was some recovery of function, this did not translate into an overall benefit.
While the data from HEBE were awaiting publication, a €5.9 million EU Framework Programme 7-funded trial, BAMI was proposed. The study aims to recruit 3,000 patients at centres all over Europe.
Another trial, AMICI, sponsored by the Australian biotech Mesoblast Ltd, is taking the technology a stage further, by using donor cells that are available off the shelf. Results of this study are not due until June 2018.
In summary, to date there is little evidence of stem cells having an effect on cardiac function, Doevendans told delegates.
Earlier this year there were also disappointing results in a trial using gene therapy to treat the damage caused by heart attacks. The Cupid trial, in which a viral vector was used to administer the gene for Serc2a, an enzyme that is involved in controlling contractility of heart muscle, was completely negative.
Doevendans believes the reason for these disappointments was that the march to the clinic was too fast. “The problem is the low standard of preclinical work,” he said. The clinical development took off on the back of enticing evidence that stem cells prompted regeneration of heart muscle in mice, before underpinning preclinical data was completed. In addition, there has been a lack of transparency, meaning only 30 percent of relevant animal data was published, Doevendans said.
This cautionary tale of more haste, less speed underlines the need for greater efficiency in drug development. “We need to get on,” said Robert Johnstone of the European Patients’ Forum. As Haerry observed, patients are not only waiting, they are dying.
Johnstone, who has had rheumatoid arthritis since he was three years old, estimates that if anti-tumour necrosis factor antibody drugs had been available when he developed the condition, the UK government would have saved around £500,000 in healthcare costs and benefits payments.
“There can be huge savings if there are good treatments,” said Johnstone. “There is no room for inertia, we need to innovate the innovation process.” The way forward is to get patients involved in making decisions, including the assessment of which innovation is most relevant. In addition, Johnstone called for HTA bodies to recognise patients as experts who live with their conditions and hold valid views on efficacy and effectiveness, and have insight on what is most cost-effective in terms of quality of life. In addition, Johnstone called for a single HTA methodology throughout Europe.
In parallel with the EMA’s work to accelerate access to advanced therapies through its Adaptive Pathways pilot, the UK regulator MHRA has set up an Early Access to Medicines Scheme (EAMS) that not only aims to speed up marketing approval in the UK for products that have completed phase II, but also to ensure the National Health Service (NHS) is poised to use products in the scheme as soon as they are licensed.
As Dan O’Connor, Medical Assessor at MHRA described, the first step in the process is securing a Promising Innovative Medicine (PIM) designation. “You need PIM to move through the EAMS – this [validates] that the clinical development programme is on track and provides the opportunity to engage with NICE [the UK’s National Institute for Health and Care Excellence] and the NHS, on access,” O’Connor said.
Following on from PIM the MHRA gives a scientific opinion under EAMS, which if positive, allows a product to be marketed in the UK in advance of centralised approval by the EMA. To date, eleven products have secured PIM designation and five have gone on to get early access.
“Patients can get access to medicines before they are licensed and prescribers have greater confidence because they know [products] have been reviewed,” said O’Connor.
In recent years the pathway of innovation has changed from a linear progression with the patient at the end of the line, to a circular process where the patient is present throughout, said Lode Dewulf, Chief Patient Affairs Officer at UCB. “Now the process is patient to science; science to solution; solution to patient,” Dewulf said.
This change presents the opportunity to address a major defect in the drug development landscape, which is the “Gaussian tyranny” that focusses on the average population. “This doesn’t recognise diversity or the fact that the average does not exist,” said Dewulf.
However, while patient engagement presents a way to ensure drug development factors in a more representative view of the likely patient population, it also presents a challenge in that development is global and patient engagement is local.
It took 20 years to harmonise toxicology requirements internationally so that a single dossier is accepted worldwide. Involving patients could once again lead to fragmentation and duplication. Patient engagement needs to go global, and to be mapped and synergised, Dewulf suggested.
The Patient Focussed Medicines Development Group has been set up to tame the “wild mushrooming” of patient engagement. The group says while stakeholders have started to develop guidelines and methodologies for improving patient engagement in medicines development, the existing approaches are fragmented. An efficient, measurable and reliable framework that involves patients as partners needs to be developed, validated and applied.
Along with taking a scientific approach to patient inputs, the pharma industry needs to build trust that it will use the information objectively and appropriately. “Engagement requires trust,” Dewulf concluded.