Personalized Medicine in Germany

By: Ankit Gurjar

Introduction

The successful completion of the Human Genome Project (HGP) in 2003 and
the fast decreasing human genome sequencing costs encouraged the
development of a new medical approach which is called Personalized Medicine
(PM).

Preventive healthcare consists of measures taken for disease prevention, as

opposed to disease treatment. A medicine or other treatment designed to prevent
disease or ill healths. Which are affected by environmental factors, genetic
predisposition, disease agents, and lifestyle choices.

Personalized medicine is a medical practice that separates patients into different

groups with medical decisions, practices, interventions and products being
tailored to the individual patient based on their predicted response and risk of
disease.

Personalized medicine focuses on tailoring treatment plans to patient groups or

individual patients with different needs. Advanced therapies are typically
custom-tailored to the individual patient and include emerging fields of
regenerative medicine, cell- and gene-based therapies and nanoscale therapies.

Personalizing treatment can help improve pharmacotherapy when the result of a

biomarker test allows to predict treatment success or the occurrence of severe
adverse drug effects with reasonable certainty. Based on the test result, a drug
is then only given to the subgroup of patients for which it is expected to be
beneficial.

The concept of personalized medicine (PM) is not new, but the term has become
a buzzword since increasing amounts of personal data, including genomic
information, can be collected, analyzed and interpreted. In a broad sense, PM
can be defined as: “The use of combined knowledge (genetics, or otherwise)
about a person to predict disease susceptibility, disease prognosis or treatment
response and thereby improve that person’s health”. Narrowly used, the term
PM refers to conditioning the use of a drug in a specific person on the presence
or absence of a predictive biomarker in the tissue or body fluids of that person.

Overview

A considerable number of personalized medicines are approved in the field

of oncology. Cancers (malignant neoplasms) are among the top five causes of
death worldwide . The only application of a PM drug affecting
cardiovascular diseases, the leading cause of deaths in high and middle
income countries, is the use of lomitapide to treat homozygous familial
hypercholesterolemia, a rare metabolic disorder that is an underlying cause of
early cardiovascular death.

Building upon these developments,the German Federal Government has

designated personalised medicine as one of six action are as in its Health
Research Frame work Programme.

WHO recommends abacavir as the preferred HIV treatment in children and,

as hypersensitivity reaction remains rare, suggests that appropriately trained
clinical staff should manage patients clinically where HLA-B*5701
screening is not feasible. Maraviroc, which may be used to treat a subgroup of
people living with CCR5-tropic HIV, is not included in current WHO guidelines
for treating and preventing HIV infection.

Personalised medicine also gives rise to ethical, legal and economic issues that
need to be addressed. For this reason, funding is also available for relevant
accom- panying research, while information and discussion platforms will be
organised and supported with broad-based participation by relevant groups from
society.

Between 2013 and 2016, the BMBF is providing up to360 million euros for
research and development projects. This funding will fnance already up-and-
running initiative singenome research and systems biology, for example,or else
will be used to initiate newfundingmeasures.This will be supplemented by the
signifcant funding for research and development on personalised medicine that
is available within the frame work of institutional support.

personalized medicine for global health

The large portion of global deaths that is attributable to risk factors

suggests that personalized medicine approaches, tailored, for instance, to
health risk data of individuals or specific groups, could affect health on a
population level globally if improved targeting of approaches resulted in more
reduction and better prevention of risks that are major contributors to the
global death and disease burden. In fact, population-wide approaches that
use, for instance, remote sensing data, cell phone data, Internet search
behavior, health systems data and/or genomic information, as part of broadly
defined personalized medicine are becoming globally more feasible due to an
expanding information base and increasing Internet access .

To improve population health globally, better or targeted interventions,

vaccines, or drugs are all areas of potential interest . Comparing application
areas of personalized medicine drugs with global mortality and health risk
patterns indicates that personalized medicine with a focus on tailoring
pharmacotherapy to genetic characteristics of individuals is of minor
relevance for global population health at present. This conjecture is
corroborated by the small number of personalized medicines included in
the 2017 WHO Model List of Essential Medicines (only nine personalized
medicine drugs, or eight substances, are among the 437 essential medicines) and
reports that access to existing essential drugs, diagnostics and preventative
measures is already insufficient in the health systems of many countries.

To further assess the role of personalized medicine for global population health,
there is need for a strong evidence base, showing, firstly, that genomics-based
personalized medicine is “at least as safe, effective and cost effective as
other, more traditional approaches, such as modifying environmental or
social determinants” and, secondly, which personalized medicine
approaches impact health on the population level.

The health care industry: Driving new products and procedures in the
Field of personalized medicine

The health care industry is already very much aware of the field of personalized
medicine. Small and medium-sized biotechnology and medical technology
companies are excelling here as innovators and are proving to be attractive
partners for medium-sized and large pharmaceutical companies. In tumour
therapy in particular, diagnostic procedures are already available that can
predict the effect of a drug and thus facilitate targeted treatment. Knowledge
gained in the area of personalized medicine can be of benefit to all actors who
wish to introduce innovative diagnostic and therapeutic agents into clinical
practice. The following specific opportunities result here for the health care
industry:

Closing of innovation gaps - Falling productivity in drug development and the

gradual expiration of patent protection for many “blockbuster” drugs are global
challenges faced by the pharmaceutical industry that are threatening the
competitiveness of German yasalocation for the pharmaceutical sector.
Personalized diagnostic and therapeutic procedures of for enormous potential to
close innovation gaps. In particular, participants in partnerships with companies
from the biotechnology, pharma and other relevant industrial sectors and with
academic research will have an opportunity to become highly innovative and
successful players in the market.

Reduction of R&D costs - The analysis of individual profiles including relevant

factors such as genes and lifestyle allows for the classification (stratification) of
patient groups and thus also for a reduction in the costs of carrying gout tailored
clinical studies with fewer test subjects. This can speed up the approval process
and, at the same time, reduce the risk of failures in drug development. New
drugs can be granted approval more quickly and become available earlier to
patients.

Optimization of the proof of effectiveness - The parallel development of therapy

and diagnosis improves the potential for fulfilling the increasingly stringent
requirements for the proof of effectiveness for therapies. Such evidence is a pre
requisite for the reimbursement of costs by statutory health insurance, which in
turn allows innovative drugs to become accessible to the majority of patients in
Germany. In addition, companion diagnostics will offer improved therapy
monitoring. In this way, treatment regimens can be adapted more quickly.

Expanded use of approved drugs - New methods in molecular biology allow for
a more targeted use of known substances and the proof of efficacy for additional
indications. In this way, the scope of applications and market potential of
approved drugs can be expanded.

Development of new therapeutic procedures and products - There is still no

causally effective treatment procedure available for many conditions. In the
future, newly developed drugs and treatment procedures could be used from
early treatment through to follow-up care of diseases in a manner more
specifically tailored for patients or patient groups. As an initial step, the
effectiveness of established procedures could be test eleven before a certain
drug is administered. The aim is significantly improved effectiveness for
treatment procedures and drugs, accompanied by a minimization of side effects
particularly in the case of multi morbid patients.

Future aspect of personalised medicine- approach Towards Personalised

Medicine for Inflammatory Skin Diseases Start of Research Project
BIOMAP
The large-scale IMI project will investigate the causes and mechanisms of
Atopic Dermatitis and Psoriasis

On 1 April, 2019, the European research project BIOMAP (Biomarkers in

Atopic Dermatitis and Psoriasis) kicks off its activities with the aim of
improving the lives of patients affected by the two most common inflammatory
skin conditions. Addressing key unmet needs in treating atopic dermatitis and
psoriasis by analysing data from more than 50 000 patients, the five-year project
will have a broad impact on disease understanding, patient care and future
therapies. The team comprises 26 academic and five industry partners as well as
five patient organisations. The Innovative Medicines Initiative, the European
Commission and the participating pharmaceutical companies provide EUR 20.8
million funding for the first IMI project in the field of dermatology.

Atopic dermatitis and psoriasis affect more than 300 million people worldwide
and are highly variable in terms of onset, severity, progression over time and
response to treatment. Resulting in significant morbidity and an increased risk
for associated conditions such as arthritis and asthma, inflammatory skin
diseases are a huge burden to patients and families, care-givers and healthcare
systems. Yet, despite many years of research, there are still significant gaps in
the understanding of both conditions.

The renowned clinicians and scientists of BIOMAP, who have now joined
forces in a large public-private partnership, will examine the causes and
mechanisms of these conditions. By analysing the largest collection of patient
data ever and performing advanced molecular investigations at the single cell
level and in the tissue context, they aim at identifying biomarkers for variations
in disease outcome. Taking advantage of recent technical developments in
translational medicine, the project will drive drug discovery and improve direct
disease management by combining clinical, genetic and epidemiological
expertise with modern molecular analysis techniques and newly-developed tools
in bioinformatics. BIOMAP is the first IMI project in the field of dermatology.

Assuming that the variation in symptoms and disease progression reflects

fundamental differences at a molecular level, the researchers will take a holistic,
systematic approach to identify patient subgroups with different subtypes of
disease and different responses to therapy. Additionally, the BIOMAP
consortium aims to examine the genetic and environmental factors which exert
additional influence on disease outcome and treatment response as well as
measurable factors in the patients’ blood and skin which reveal the disease
subtype they belong to. In an unprecedented analysis of harmonised clinical and
molecular data from more than 50 000 patients as well as healthy individuals,
the BIOMAP researchers aim to derive a new model for disease classification in
order to provide each patient with optimal treatment and an individualised
therapy scheme.

Professor Stephan Weidinger, academic coordinator of the consortium and

internationally-renowned clinician scientist from the University of Kiel
Germany, hopes that “atopic dermatitis and psoriasis will be identified as a
series of different diseases rather than just one disease, each with a
characteristic molecular ‘signature’.”

Dr Paul Bryce, the consortium’s project lead from Sanofi, states that “by
understanding these diseases as comprehensively as possible, any molecularly
defined endotypes we will find will help to drive the next generation of
precision therapies that can improve the lives of patients.”

“The findings from BIOMAP will drive rapid drug discovery to target causal
mechanisms, and will pinpoint biomarkers which can support clinicians to
decide who, when and how to intervene”, expects BIOMAP’s academic co-
coordinator Professor Catherine Smith from King’s College London.
“BIOMAP will help us to better understand the relationships between inherited
susceptibility, environmental factors, and molecular profiles, as well as the roles
of each of these in onset and progression of the diseases”, says Dr Witte
Koopmann, industrial co-project lead from LEO Pharma.

The voices of patients living with Atopic Dermatitis and Psoriasis will be at the
heart of BIOMAP, through the establishment of a Patient Advisory Group. It
will ensure that patients’ insights, opinions and wishes are taken into account
across all the multiple components of the project.

Helen McAteer, Chief Executive of the Psoriasis Association and member of

the BIOMAP Patient Advisory Group, described the ambition and purpose of
BIOMAP as “a major opportunity to improve the lives of people with skin
disease – we need information on why and who is going to develop severe
disease, and also new approaches to treatment. Involving a Patient Advisory
Group puts the needs of the patients at the heart of the project from the very
beginning. By providing a European-wide platform for collaboration, BIOMAP
will enable sharing of know-how and data about atopic dermatitis and psoriasis
so that we can all work together like never before”.

BIOMAP is funded by the Innovative Medicines Initiative 2 Joint Undertaking

under Grant Agreement No. 821511 and in-kind contributions of the
participating pharma companies. The Joint Undertaking receives support from
the European Union’s Horizon 2020 research and innovation programme and
EFPIA.

The project will officially kick off its activities with a first meeting in London
on 10-12 April, 2019

Helen McAteer, Chief Executive of the Psoriasis Association and member of

the BIOMAP Patient Advisory Group, described the ambition and purpose of
BIOMAP as “a major opportunity to improve the lives of people with skin
disease – we need information on why and who is going to develop severe
disease, and also new approaches to treatment. Involving a Patient Advisory
Group puts the needs of the patients at the heart of the project from the very
beginning. By providing a European-wide platform for collaboration, BIOMAP
will enable sharing of know-how and data about atopic dermatitis and psoriasis
so that we can all work together like never before”.

BIOMAP is funded by the Innovative Medicines Initiative 2 Joint Undertaking

under Grant Agreement No. 821511 and in-kind contributions of the
participating pharma companies. The Joint Undertaking receives support from
the European Union’s Horizon 2020 research and innovation programme and
EFPIA.

The project will officially kick off its activities with a first meeting in London
on 10-12 April, 2019

Formulate entry strategies accordingly

Once the type of regulatory environment for personalised medicines in each

country is known, pharmaceutical companies can take proactive steps to assist
the assessment and reimbursement of personalised medicines accordingly.

Based on our extensive project experience, each case can be evaluated on its
own merits. For example, a recent evaluation of a new molecular diagnostic in
Germany assessed several factors, including the business case for the test
(including its budget impact and cost-effectiveness), its level of support from
the medical community to approach the national hospital remuneration system
directly, and its reimbursement potential in the current environment, and
concluded there was an optimum type of contract it could hope to achieve. In
another assessment of an in vitro diagnostic in oncology, the main value drivers
influencing the funding / reimbursement were identified, which included the
predictive value of a test, its reproducibility and positive effects on patient
outcome.

After the evaluation process, companies can conduct public policy efforts to
encourage joint assessment and adequate assessment methodology, bridging
strategies to improve market access through programmes and tools that
demonstrate value, or develop joint data by adapting the evidence generation
process early in the treatment pathway. Ultimately for coordinated and joint
assessments, frameworks are required which allow the linkage of different types
of evidence and provide policy makers with fewer evidence gaps to reduce
decision-making uncertainty.

Perhaps the most fundamental issue is a lack of holistic view within

healthcare regulatory systems.
To determine whether the biomarker test, the drug, both, or neither should be
subsidised, the framework states it is crucial to identify whether the biomarker
is a treatment effect modifier or a prognostic factor. To aid in this
determination, the framework explicitly allows the linkage of different types of
evidence to examine whether targeting the biomarker varies the likely clinical
benefit of the drug, and if so, to what extent. This kind of flexible, coordinated
review system is ideal for the assessment of personalised medicines. The
challenge is that it requires direct or linked clinical evidence for the treatment
and diagnostic, and requires economic evidence along the treatment path
including alternative diagnostics. Within Europe, the UK is currently piloting a
similar approach.
Broadly speaking, countries in Europe will start to fall into one of these three
categories – a separate assessment such as in Germany, a more coordinated
assessment such as in France, or an entirely joint assessment such as that in
Australia / the UK
Challenges ahead
Although personalised medicine represents a positive development for all
stakeholders, many healthcare systems across Europe are not set up to evaluate
treatments and their companion diagnostics in the holistic manner so essential to
their success. Hence, pharmaceutical companies and diagnostics producers need
to collaborate tightly to generate the necessary evidence and obtain adequate
reimbursement. It is therefore important to assess individual markets early
enough before submission and identify potential entry strategies which will
maximise the chance of market access.

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• https://www.researchgate.net/publication/264837319_Citizen_Scenarios_
for_the_Future_of_Personalized_Medicine_A_Participatory_Scenario_Pr
ocess_in_Germany
• https://www.gesundheitsforschung-
bmbf.de/files/Action_Plan_IndiMed_englisch.pdf
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932462/
• https://www.executiveinsight.ch/en/insights/personalised-medicine-
uptake-challenges
• https://www.dzif.de/en/personalized-
medicinehttps://www.bundesgesundheitsministerium.de/english-
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