A Road Map for Increased Innovation in Pharma

19
A Road Map
for Increased
Innovation
in Pharma
EXECUTIVE
SUMMARY
Acknowledgements
Our thanks to Mr. Carlos Gil, Journalist specializing in health,
Director of Gestiona Salud (Gestiona Radio) and author of this
publication:
without his collaboration, this publication would not have
been possible.
We would also like to thank the members of the Future Trends
Forum (FTF) who made the forum a success, and a special
thanks to those who contributed to the chapters of this publication.
For their invaluable support in the composition of this publication:
Mr. José María Fernández Sousa, President of Zeltia Group
Ms. Elvira Sanz, President of Pfizer Spain
Mr. Andrew Hessel, Distinguished Researcher, Singularity
University
Mr. Alpheus Bingham, CEO of Innocentive
Mr. Emilio Méndez, Center for Functional Nanomaterials at the
U.S. Department of Energy’s, Brookhaven National Laboratory
For their invaluable role in the methodology and organization
of the Future Trends Forum:
Mr. Christopher Meyer, Founder Monitor Talent
Mr. Garrick Jones, Partner Ludic Group
Mr. Fernando de Pablo, Designer of Bankinter
Finally we would like to thank the members of the Fundación
Innovación Bankinter team for their commitment and follow
through in the development of the content of this publication:
Fundación de la Innovación Bankinter
Mr. Juan Rosas
Mr. Sergio Martínez-Cava Ms. María Teresa Jiménez
Ms. Lara García de Vinuesa
Ms. Dorsey Lockhart
Mr. Nabil Banhaq
Ms. Marce Cancho
Many thanks,
Fundación Innovación Bankinter
Introduction
The cost of developing drugs has increased exponentially over the last
few years, both investment and time-wise. Today, marketing a new
drug takes 12 to 16 years, and costs around $1 billion. Additionally,
governments are reluctant to pay the bill for new compounds, due to
economic uncertainty worldwide and the growing burden of health care
on public budgets. Shareholders call for greater caution among pharma
companies when taking on risks, since only one in three substances that
makes it to stage 3 of clinical trials—decisive for administrative approval—becomes a marketed drug, despite having already invested up to 60
or 70% of the cost of the entire process by then.
Therapeutic progress introduced by the pharma industry over the last 70
years has yielded an unprecedented improvement in life expectancy in
developed societies. But ageing comes at a cost, since 80% of healthcare
costs generated by a person throughout their life is when they reach 65
years of age and older.
Drug development—an indisputably leading sector in R&D worldwide—is
facing a crossroads today: research productivity has fallen down to a point that threatens the development of innovative drugs, and raises the
question of whether the conditions to reimburse such therapies will be
there in the medium term.
The XIX Future Trends Forum, “The Future of Drug Discovery” has
brought together representatives of the pharma and biotech industries,
startups, basic research, business management, investment funds, open
innovation, public administrations, patients, and new technologies…
The goal is to carry out an impartial analysis of what fields or tools will
ignite a revolution in drug development, what business models will solve
structural problems, what the priorities in public and private research
are, what the solutions to align knowledge and innovation are so that
the chance of transforming them into products increases, and what alternative access to funding there is in a complex environment…
In short, the XIX Future Trends Forum has taken on the challenge to devise the roadmap toward a future where drug development becomes once
again the undisputable driver of innovation and R&D in healthcare gains
back a sustainable framework. This roadmap comes along with specific
proposals to make it a reality and consequences for multiple stakeholders (citizens, patients, regulators, industry, research centers…). It aims
to detect the incentives that will spur their implementation.
3
4
Disruptive Technologies:
The Innovation Roadmap
The investment needed to develop a new drug today is over €800 million. However, only one in five becomes a blockbuster. Hence, the
pharmaceutical industry is facing the challenge of finding unchartered
fishing grounds of innovation to provide more effective solutions for
the needs of patients, and guarantee a return on a long-term investment. For the XIX Future Trends Forum attendants, those disruptive
technologies are: synthetic biology, biomarkers, genetic information,
high-throughput screening and bioinformatics, cell therapy, and nanotechnology.
In the case
of cancer,
for example,
biomarkers
indicate what
particular type
of tumor is, at
what stage it is
and what the
probabilities
are of various
evolutions, as
well as what
drugs will
work or not for
this particular
patient.
Of these technologies, synthetic biology probably is the least developed, but it already opens up the possibility of using genetically-modified bacteria to treat chronic inflammation or send signals to the brain
to modulate hunger.
Biomarkers are a thriving field. In the case of cancer, for example, biomarkers indicate what particular type of tumor is, at what stage it is
and what the probabilities are of various evolutions, as well as what
drugs will work or not for this particular patient.
High throughput screening and bioinformatics are changing the way
we know the genome. The initial human genome sequencing took ten
years and $3 billion. Today, you can analyze a patient’s genome in five
days for slightly under $10,000. This information enables personali-
zing therapies and unraveling the molecular bases of diseases to find
out how to tackle them more effectively.
Nanotechnology will change diagnostics by detecting substances that
reveal an early-stage disease long before symptoms are present, and
it will change treatment by administering lower doses of drugs accurately to the affected tissue, obtaining greater efficacy and fewer side
effects, since healthy areas will be preserved; or by enabling the administration of insulin in one daily dose released based on what the body
needs, instead of the current 16 daily interventions to measure sugar
levels and administer the drug.
Cell therapy was first used four decades ago in bone marrow transplants, although it has become more prominent at present in embryo-
nic stem cell basic research, clinical trials with adult stem cells and the
discovery in 2006 of induced pluripotent stem cells, a finding worthy of
the Nobel Prize in Medicine 2012. From myocardial infarction to cancer
and osteoarthritis and multiple sclerosis, cell therapy has the potential
to become the foundation of regenerative medicine.
Knowing genetic predispositions will enable patients to adopt preventive,
healthy lifestyles, which will give them greater control over and an active
engagement in their own health, and will free up resources for research.
Resource Allocation and
Innovation: Public Sector,
Private Companies and
Patient Needs
Single-drug
company,
focused on
developing
one single
drug, made up
of three to ten
researchers
with a
profound
understanding
of the disease
and the
substance
tested
The XIX Future Trends Forum has explored original ways to allocate resources in order to maximize innovation. One example in the public sector
is DARPA; a US Government agency established by the Department of Defense to promote basic research and technology-based projects that can be
used directly in matters of national security. It touches upon several areas,
from developing new materials to sensors and communications, as well as
photonics, and of course, biomedicine. DARPA focuses on developing capabilities that are currently non-existent, and creating alliances to develop
them with the widest range possible of institutions: from multinationals
to university laboratories and biotechnological companies. Among its projects, there are vaccines based on RNA technology that can be mass-produced in a short time frame once a new pathogen has emerged; portable devices that produce universal donor blood and new ways of collecting blood
samples to carry out fully remote clinical trials.
One proposal from private investors is the single-drug company, that is,
a company focused on developing one single drug, made up of three
to ten researchers with a profound understanding of the disease and
the substance tested. Big companies would provide funding and technical assistance. These structures—fully focused on patients’ needs, not on
artificially opening new markets—would market new drugs under $100
million, that is, one tenth of the current cost.
5
Over the last few decades of the 20th century, drug research and development strategies are being enhanced with a new, very active player:
patients, who have gone from being passive subjects, receiving individual care and unconnected to each other, to creating organizations that
give their pathology visibility, give them a say in the public discussion,
and make them stakeholders in the decision-making process. The Spanish Federation of Rare Diseases (FEDER by its Spanish acronym), is a
paradigmatic example.
In fact, it represents pathologies that do not have critical mass to be of interest to the pharma industry. However, their organization as a federation
has built a community that represents 3 million citizens only in Spain,
and may propose diagnosis and research strategies at a European level.
6
Academia-Industry Alliances:
an Open Innovation Model
University
hospitals are
the usual
headquarters
of clinical trials.
Their dynamics
may improve
substantially
thanks to
biomarkers
Now, more than ever, the demand for truly transformational therapies
and increasing development costs call for an association between university research centers—commonly known as academia—and the pharmaceutical industry, for the benefit of society as a whole .
The future of this relationship is approached as a model of synergies. The
Nestlé Institute of Health Sciences being one example, but there are others,
such as the one promoted by the Karolinska Institute and Astra Zéneca.
Another one is Enlight Biosciences, created by several pharmaceutical multinationals and relevant researchers from Harvard, the MIT, and the big
hospitals in the Boston Area. Consortia under the European Framework
Programme for research are also building on efforts from both sides.
University hospitals are the usual headquarters of clinical trials. Their dynamics may improve substantially thanks to biomarkers. First, biomarkers enable a more accurate identification in the preclinical stage of the
molecules with the highest potential to become drugs. Thanks to biomarkers, human participants in trials are better selected, the substances with
the greatest efficacy can be identified through the trial, and toxic ones can
be discarded. This adaptable design may potentially reduce the number of
patients in the final stage to one tenth and more than double the efficacy
of the resulting drug, hence reducing costs and optimizing research.
The Role of Start-ups in
Innovation
Start-ups are replacing big pharma as a source of findings that lead to
Thanks
to their
structure,
start-ups
can fund
their early
steps with
public funds
or business
angel, and the
company can
be windeddown at the
right time,
that is, before
committing
great
investments.
the approval of new drugs. Thanks to their structure, they can fund
their early steps with public funds or get the support of a business angel, and, if future studies thwart initial expectations, the company can
be winded-down at the right time, that is, before committing great investments.
Funding is a problem in the short-term, since both venture capital and
pharmaceutical multinationals are investing in advanced stages of development. Public aid to research and private foundations and even pa-
tients’ associations are emerging as alternatives.
Startups need financial and also managerial support. Lack of training
or advice in this regard can thwart no few developments. On a different
note, universities must welcome greater multidisciplinarity to encourage innovation and create operational departments to manage intellectual property, alliances with the industry and business development.
Information contributed by patients themselves through platforms
such as 23andMe where, aside from paying for your genetic analysis
you can donate your anonymized data for research purposes) and PatientsLikeMe are generating a phenomenon known as “crowd-sourced
science”, similar to “crowd funding”, where individual contributions
that would not be very useful by themselves, multiply their capacity to
add value exponentially—in this case, knowledge—when adding tens of
thousands of people.
7
8
Seventeen Impactful Proposals
to Promote Innovation in Drug
Development
Reducing costs in Stage 3 of clinical trials
01
02
03
04
Tapping into the opportunities of Electronic Clinical Records to improve and automate candidate selection for clinical trials.
Relying more—and better—on biomarkers to adapt the design of the
trial to the results as they become available.
Promoting remote clinical trials: they reduce costs and are more convenient for patients.
Standardizing and integrating data on the evolution of the disease
and the clinical trial.
Tomorrow’s business models
05
06
07
08
Introducing the single-drug company model as a way to regain efficiency and productivity in R&D.
Choosing alternative sources of funding: seed capital, patients’ associations, securitization…
Evolutive capitalization and flexible sizing of projects originated in
academia as research results that are appealing to investors become
available.
Multiplying the range of products while reducing the risk for traditional investors, such as multinational pharma companies.
New markets: the engaged patient
09
Aligning the theoretical and real markets by encouraging therapeutic
compliance, not only to increase the financial solvency of this industry, but also to guarantee an essential public health goal.
10
11
Using the stream of data generated by patients for new lines of research.
Creating additional markets through new channels to dialogue
with patients.
Promoting start-ups
12 Creating a culture that values risk and radically changes the individual and social perception of failure, so that it becomes a regular
mechanism to boost the economy.
13
Supporting startups with suitable legislation and fiscal regime, especially regarding tax incentives and administrative agility to start
up companies.
14
Looking for new types of alliances with the pharmaceutical industry.
15
Reinforcing relations with academic research.
Shortening development times
16 Breaking the clinical trial paradigm and seeing it as a continuum where
design adapts to results as they become available.
17
Unifying criteria among authorization-granting agencies, since having
certain time frames, conditions and reimbursement is essential to obtain
a return on investment.
9
10
The Future of the Value Chain
in Drug Discovery
What implications will have a scenario where these measures become
a reality for civil society, political decision-makers, the pharmaceutical
industry, university research labs and other players in the field?
Citizens would have greater decision-making capacity on their own
healthcare decisions, thanks to information on genetic predispositions.
They may even directly promote research funding. In time, new social
debates cannot be ruled out: sustainability of the healthcare system,
granting or denying care based on one’s personal responsibility for one’s
own health, allocating and prioritizing resources…
In biomarkers, the pharmaceutical industry will find an easier path
towards new drug discoveries with greater efficacy and fewer side
effects, which will benefit its social standing. There is still the question
of the business model in an environment where drugs are more expensive and the target population is smaller. This yet unanswered question
includes possible changes to the current picture of pharmaceutical multinationals.
New business models benefit academic research and lure more talent
In biomarkers,
the pharmaceutical
industry will
find an easier
path towards
new drug
discoveries
with greater
efficacy and
fewer side
effects
to research. A pharmaceutical industry more engaged in academia may
have a positive impact on issues that universities have traditionally neglected, such as putting together multi-disciplinary teams and creating
incentives linked to results.
Patients’ associations (in its myriad ways) are increasingly influential
on society; they are a highly valuable source of aggregate data to gene-
rate knowledge and drug development and may reveal themselves as a
player that is fully capable of co-funding early-stage research projects.
If the scenario proposed by the participants at the XIX Future Trends
Forum becomes a reality, the market would have more drugs and would
meet more clinical needs thanks to new therapies. Above all, the market would have greater transparency, because it would be known what
percentage of patients will respond favorably to drugs, or the percentage
that will develop drug toxicity—once again, thanks to biomarkers. Transparency is a key factor in the degree of public satisfaction with healthcare spending, especially when the expenditure increases.
An environment must be created where information on failed clinical
trials is shared. Today, those data remain unused because of the confidentiality terms imposed by sponsors when the expected results are
not attained. However, they are a highly valuable source of knowledge
to avoid duplications in research, which prove to be very costly in terms
of funds, time, effort, and talent that could be used in other areas.
Knowing what has not worked and why is almost as useful as knowing
what has worked.
Political decision-makers face questions such as how to avoid genetic
discrimination, guarantee access to healthcare data, achieve data and
sample sharing for research purposes, offer tax incentives to international research, a smoother integration of the various aspects of scientific
policy and encourage public-private cooperation.
11
www.fundacionbankinter.org