Kate Moss
Session chair: Martin Ince
Reporter: Andrew Smith
Keywords
Biomarkers, Biosimulation, Collaboration, Live license, Nanotechnology, Pervasive monitoring
The current fashion among conference organisers is to include, at some point in the programme, an ‘inspirational speaker’. While attending clinical research conferences over the past few years, I have heard from astronauts, athletes and Antarctic explorers; they prompted admiration and interest, and sometimes inspiration on a purely personal level, but I have often struggled to connect these people’s achievements back to my own professional life. This keynote lecture, given towards the end of this year’s ICR conference, was entirely different in that it was both personally and professionally inspiring. In just half an hour, Kate Moss of PricewaterhouseCoopers (PwC) challenged us to suspend our natural scepticism and our mental and organisational silos, and offered us a glimpse into a possible future for drug development. In retrospect, that future seems as radical and different from how we work today as our modern ‘industrialised R&D’ would probably look to a pharmaceutical research physician from the early 20th century.
Kate’s presentation drew from the ‘Pharma 2020’ series of reports published by PwC over the past few years. These broadly argue that changes to the research environment and the global market for pharmaceuticals necessitate a significant change in the way pharma companies operate, and suggest one possible response to this.
The current model is broken
She started by describing the shift in decision-making from prescribers to payers and policy-makers, and the increasing importance of demonstrating value for money alongside safety and efficacy. While the global market for medicines is growing, it is also becoming increasingly heterogeneous, particularly in the developing world. Conversely, productivity in R&D is decreasing, the regulatory framework is getting tighter, and employee incentives don’t work in an increasingly team-oriented environment. Ultimately, the US market, which has arguably subsidised the rest of the world for many years, will no longer be able to do so. Kate showed us some well-known (but nonetheless depressing) graphs demonstrating increasing R&D costs, decreasing new approved medicines and the multi-billion dollar decrease in revenues due to patent expiry and generic competition over the next few years. All of these factors mean that pharma needs to transform how it operates to adapt to the future landscape.
In response to this, Kate predicted a sharpening of the current innovative/generic division, with some organisations specialising further in ‘commoditised’ products (eg, new line extensions and branded generics) aiming to achieve high volume sales by managing symptoms while others take a more innovative, physician-led approach to cure conditions by develop high-cost therapies with increased risk-sharing between producers and payers. She concentrated on the latter segment for the remainder of her presentation.
The pharmaceutical industry currently spends just over $80bn on R&D, and this is expected to grow to over $200bn by 2020. However, as much as 40% of current spending is on line extensions for existing products. Kate called for a significant change in how R&D is conducted. We are already seeing collaboration increase between industry, academia, regulators, government and healthcare providers, but this will need to increase significantly to achieve the “seismic shift” of transformative change that Kate thinks is necessary.
Virtual R&D
Having given us a
detailed description of the problem facing us all, Kate outlined some
aspects of a possible solution. The most far-reaching scientific
proposal was the development of a single validated computer model of
the molecular and cellular components of the human body. Her vision is
to use such a model to simulate the effects of medicinal molecules on
specific disease targets to identify which targets are relevant, and
predict ADME, side effects, dosage and the balance between efficacy and
safety. Doing this in a virtual environment could accelerate the early
stages of drug development, complement (or replace) animal studies, and
give greater confidence for first-in-human and proof of concept
studies, while reducing operational costs.
While this might sound implausible, Kate gave examples of three organisations that are already working toward this sort of goal:
- The Step Consortium (www.europhysiome.org), which is based upon viewing the human body as a single complex system.
- The Living Human Project (www.livinghuman.org), which has started to develop an in silico model of the human musculoskeletal system.
- The Physiome Project (www.physiome.org.nz), which aims to develop integrative models at all levels of biological organisation, from genes to the whole organism.
Pervasive patient monitoring
Kate
spoke of the need to shift our mindset from treating symptoms to curing
and ultimately preventing disease. This is already happening in areas
such as gene therapy and regenerative medicine, and nano-therapeutics
is also an exciting area, working to deliver therapeutics (or even tiny
repair ‘robots’) to specific cells or organs.
Biomarkers are already being developed and used in
diagnostics and increasingly to measure the impact of treatment. Once
validated as reliable surrogates, they can be used extensively to
select patient sub-populations and to monitor the course of a clinical
trial. This becomes even more compelling when combined with
nanotechnology; Kate envisioned implanted nano-devices equipped to
measure biomarkers and communicating with wireless networks to provide
real-time feedback. This form of pervasive monitoring could be used to
record data into an EDC system, improve compliance, provide feedback on
adverse events or even trigger delivery of medication.
Expediting development
The next
part of Kate’s presentation discussed ‘live licensing’: a concept
that’s been around for a few years, and extends the model already used
in developing some oncology compounds. This requires much closer
collaboration between all stakeholders (ie, pharma and regulator, but
also healthcare providers, payors and patients) much earlier in a
product’s development. All need to agree on a development programme
that will provide information that each party will require at the
appropriate point in the value chain, including outcome data and broad
assessment of economic impact (ie, including indirect costs of delivery
and benefits to society). This should be agreed as early as possible
(eg, once the sponsor has confidence in the basic mechanism of action),
to ensure that the development answers the right questions for all
involved.
Rapid studies in ‘virtual’ human models and
tightly-specified patient populations would follow to demonstrate a
level of confidence in safety and efficacy. Kate suggested that this
could be done using adaptive methodology across 20-100 patients, and
take around 1 year. Data from this phase would be submitted to
regulators automatically and assessed to (hopefully) result in a ‘live
license’ to launch the product for limited clinical use in that
population. This could be as early as 18 months after beginning
first-in-human studies.
Pervasive monitoring would be used to collect data
from all patients receiving the therapy, which would flow back into the
regulators’ database. As data is accumulated, confidence in safety and
efficacy should increase, enabling the license to be extended
automatically to cover broader patient populations and indications as
appropriate.
This model would have a significant impact on the
financial profile for a product’s lifecycle, with faster time to market
lowering the initial investment and automated indication extensions
producing stepwise increases in revenue. As we move beyond the era of
the ‘blockbuster’, this sort of profile is more attractive than the
current model, where high initial costs require even higher revenues in
the last few years of patent protection. Lower pre-launch costs could
also make therapies for rare diseases etc. more economically viable.
Collaborate or die
The
technological changes Kate proposed are huge, and it would be
impossible for even the largest of ‘big pharma’ companies to attempt
this single-handed. As we are seeing with the development of biomarkers
and more formal projects such as the FDA Critical Path Initiative, the
EMEA Roadmap to 2010 and the EU/EFPIA Innovative Medicines Initiative,
large collaborations across industry and with regulators can work. Kate
called for this to be extended many-fold to reinvent the way we develop
new treatments: research and usage would become essentially seamless,
and data would be generated, captured, integrated and analysed to
enable the most effective use of healthcare, both clinically and to
society as a whole. This would be underpinned by common data standards
and predictive biosimulation models. Clearly, pharma cannot do this
alone.
Kate characterised innovation as a “team sport”,
where all decision-makers from investors and manufacturers through to
prescribers, patients and payors must be confident that the evidence
generated answers the questions that are important to them. Pharma will
need to collaborate extensively and transparently across an integrated
healthcare value chain to deliver medicines that people will want to
pay for. To do this, pharma will need to stop trying to do everything
itself and work with a network of organisations to build knowledge and
understanding about the human body and the pathophysiology of disease.
Conclusion
Ultimately, though, it
doesn’t matter if Kate and her team turn out to be entirely wrong in
their predictions (although I expect that not to be the case!) What
matters is that we as a profession are challenged out of our mindset of
incremental improvements in a business model that is ultimately
breaking down as a result of socio-economic change. It takes someone to
zoom out to look at the picture in the biggest possible terms to chart
a course out of our post-blockbuster doldrums. Her specific predictions
were stimulating, but moreover her vision was grand without seeming
utterly impossible, and the overall effect was truly inspirational.
Kate Moss is Director in Advisory Practice and Clinical Research R&D Expert at PricewaterhouseCoopers.
Martin Ince is a science journalist and broadcaster.
Andrew Smith is Editor of Clinical Research focus.
