The Danish Approaches for Personalised Medicine

The Danish Approaches for Personalised Medicine – For the Benefit of Patients

The term tailor-made or personalised medicine covers a form of drug treatment in which the use of drugs is adapted to the individual patient's very special disease situation and biological characteristics. The desire is to achieve a unique treatment result that best meets the individual patient's genetic profile. The Danish healthcare system offers unique possibilities for realising the potential of personalised medicine. Based on a common national information infrastructure, the new genome centre in Denmark will ensure the entire setup for collecting samples from patients for genome sequencing and analysing data for research or treatment purposes. The data and research will be used to identify medicines that have the best effect on different diseases and patient groups. Together with data from existing national registries and databases, as well as the national biobanks, Denmark has established a solid national framework to develop tailored personalised medicines to benefit patients.

Not All Medicine Benefits All Patient Groups Humans are not alike, which is why we often react differently to the same medicine. One of the great benefits of personalised medicine is that the quality of treatment will increase significantly. It will be possible to give patients the treatment that gives the greatest possible effect the first time, while reducing the risk of side-effects. This will improve the patient's quality of life. With personalised medicine, it is possible to achieve more health for the money, as patients receive correct medication the first time. Unnecessary money is not spent on costly medications that are not effective or perhaps even harmful to the patient.

A large proportion of the medicines offered in healthcare today do not work or are directly harmful to the patient. It is both stressful for the individual patient and a socio-economic challenge.

This is a global problem that is also manifesting itself in the United States, among other places. Figure 1 is from a US study conducted by the US Food and Drug Administration (FDA) and illustrates the proportion of patients who do not benefit from the medication they receive for their disease. Why Personalised Medicine The term "personalised medicine" was first used in April 1999 in an article in the Oncologist: "New era of Personalised Medicine - Targeting Drugs for Each Unique Genetic Profile"1. Since then, and especially in the last few years, the number of scientific articles specifically dealing with personal medicine has grown steadily, so that today hundreds of articles on the subject are published every year.

Figures from the United States compiled by the Food and Drug Administration (FDA) show that 12 out of the 48 new drugs approved in 2019 were in the personal medicine class – that is, 25 per cent of all new drug approvals2. While the total percentage of personalised medicines approved by FDA decreased from both 2018 (42%) and 2017 (36%), the FDA approved many new indications for existing, approved personalised medicines, providing new treatment options for many patients. And furthermore, several biosimilars for personalised medicines were also approved. The development in personal medicine is therefore not just a future scenario – it is reality here and now.

Diseases develop differently from patient to patient, who in turn respond differently to the same medication. Some need one tablet, while others need two tablets for it to have an effect. Some people benefit from a standard treatment – while others simply experience side-effects. One perspective when using personal medicine is that medicines are only given to those patients who are known to have an effect on the medicine – this is already seen today in connection with the use of certain cancer medicines.

Another perspective is that one can predict via molecular diagnostic tests whether a patient will have the desired effect or experience serious side-effects with a given drug treatment. One step is therefore to have knowledge of a drug that is particularly effective in relation to patients with a particular genetic profile. Another step is to have a test that can determine if the specific patient has a genetic profile that matches the use of the desired drug. Therefore, drug and concomitant diagnostic tests are usually closely related when talking about personal treatment – illustrated in Figure 2.

The use of personalised medicine was previously most prevalent in the treatment of cancers. This makes sense, since cancer is one of the therapeutic areas that has the most ineffective drugs for treatments (Figure 1). However, today the treatment principle is being transferred to many other disease areas. In 2019, there were a significant number of approvals for the treatment of non-cancer disease. Seven of the 12 new personalised medicines drugs, approved by the FDA in 2019, were for indications outside the field of oncology. This includes the approval of ZolgensmaTM (onasemnogene abeparvovec-xioi) for the treatment of spinal muscular atrophy. This gene therapy corrects bi-allelic mutations in the SMN1 gene2 . The Danish Approach to Personalised Medicine Many countries, like Denmark, are in the process of developing strategies for personalised medicine. One of the first initiatives in the Danish Personalised Medicine Strategy was the establishment of a National Genome Center in May 2018. The National Genome Center provides genomics-based analysis and insights related to diagnostics of relevant patient cases at Danish hospitals.

The establishment of the National Genome Center means that Denmark will be able to raise the overall effectiveness of personal medicine across the entire healthcare system to a level that would otherwise take a long time to achieve within individual hospitals. The Danish effort is unique in three areas. Denmark focuses on personal medicine benefiting patients immediately. In addition, the country has public control over the use of information from all Danish patients3. And finally,

Figure 1. Percentage of patients for whom drugs are ineffective Denmark develops personal medicine nationally, which means that patients receive the same treatment opportunities, no matter where in Denmark they received healthcare services.

The new National Genome Center’s supercomputer system has been established, and the centre has tested and prepared a new, national infrastructure, which consists of a national whole genome sequencing centre and a high performance computing centre. Selection is already underway for the first patient groups to be offered comprehensive genetic analyses (whole genome sequencing).

Over 80 per cent of medical specialists today use genetic diagnostics4, and the National Genome Center will ensure that they can perform comprehensive genetic examinations at a uniformly high level of quality, no matter where in the country the patient receives treatment. With joint efforts, doctors and health researchers will have better conditions for improving the treatment of future patients. Is Data Secure? A question that was very quickly asked by the Danish population was whether data from the National Genome Center is secure. In the wrong hands, DNA could be misused and harm the individual citizen. For that reason, today the National Genome Center acts under two different legal frameworks: health legislation and personal data legislation. Data is protected through two levels of security. First, at a system level, the core of the infrastructure is a supercomputer system with enhanced security features. Second, at an individual level, patients must first be informed of the patient's right to self-determination over his or her genetic information, which is derived from biological material in connection with patient treatment and which is kept by the National Genome Center. The patient can decide for themselves whether to consent to having genetic information stored in the National Genome Center, which may only be used for one's own treatment and for purposes that have an immediate connection to it. Patients may also consent to have their data used for such activities as research. The National Genome Center again has no commercial interests, which means, among other things, that the information in the National Genome Center may not be used by insurance companies. Data Analytics Center – First of its Kind in Europe For many years, the Danish healthcare system has systematically collected data and knowledge about the Danish population's diseases and treatment. It has helped researchers and health authorities to better understand which treatments work, and which do not5. Users of the Danish healthcare system expect treatment that offers them the best possible outcomes. Therefore, another component of the personalised medicine strategy in Denmark involves the establishment of a Data Analytics Center, under the Danish Medicines Agency, which will open November 2020.

The Data Analytics Center will be the first of its kind in Europe, supporting regulatory decision-making as well as creating a globally unique research infrastructure to be used by industry partners. With the Data Analytics Center, the Danish Medicines Agency is able to offer more precise scientific advice to the pharmaceutical companies in the development of new medicines, including medicines for people with rare diseases or small patient groups.

The new centre is especially relevant in Denmark, since the public health service system includes numerous comprehensive registers and statistical databases of extremely high quality – not least Denmark’s national personal identification number system6. This means all residents in Denmark are registered with the public health service system and other health organisations where they are receiving treatment.

The Danish national personal identification number system and the numerous statistical databases, disease registers and journal records offer unique opportunities for epidemiological research of extremely high quality. Given that the aforementioned registers have a long history in Denmark, Danish researchers also have a long tradition of performing register research, public health studies, and epidemiological research, all of which are important prerequisites for the identification and segmenting of relevant target segments and patient populations within personalised medicine.

With the development of the Data Analytics Center, the regions and universities will have obtained secure, confidential, and flexible access to the use of health data. This means more accurate diagnostics and better treatment for the patient. The goal is more use of personalised medicine in the Danish healthcare for the benefit of all patients.

The Danish National Biobanks Biobanks are an important component of personalised medicine, and strongly support scientific progress in the strati-

Figure 2. Standard treatment vs. personalized medice

fication of the population, biomarker discovery, and validation to drive progress in personalised medicine. Furthermore, biobanks are also an essential tool for new drug discoveries and drug development and play an important role in the whole process of patient prevention and prediction, follow-up, and therapy monitoring and optimisation7 .

Denmark has several national biobanks. The aim of these is to provide an easy, transparent and safe entrance to biological material in Denmark. The Danish national biobanks create an infrastructure that supports diagnostics and research, based on collaboration across the country to help make personalised medicine a reality; another important factor in the Danish Personalised Medicine Strategy.

The Danish national biobanks contains register with detailed information on the specimens available in the biobanks, which are physically located in the pathology departments at the hospitals around in Denmark. Danish registers provide detailed information about the entire population. Linking biological specimens in the biobanks to information contained in the Danish registers creates unique possibilities for research. Conclusion Being able to develop new pharmaceutical products is essential for successfully developing new therapies in the emerging paradigm of personalised medicine. Individualised and tailored treatment is necessary for patients to receive the right treatment the first time, manufactured to fit optimally with any unique genetic profile. The Danish National Strategy for Personalised Medicine supports the use of genomic data to offer patients more targeted and efficient medicine. Denmark's electronic healthcare data for the entire population, which goes 40 years back in time, connects to the Danish Biobank Register of 25 million biological samples. These linkages between these data sources generate a unique patient identifier system, a key enabler for personalised medicine at a national level in Denmark. REFERENCES

1. Langreth R, Waldholz M et al. New era of personalised medicine: targeting drugs for each unique genetic profile. Oncologist (1999) 4 (5) 2. Mullard A. 2019 FDA drug approvals. Nature Reviews Drug Discovery (2020) January (19) 3. Beedholm-Ebsen R. Denmark - The Heart of Life Sciences for Clinical Trials. International Pharmaceutical Industry (2013) 5 (1) 4. Lundgren B, Løngreen P. www.altinget.dk/ sundhed/artikel/nationalt-genom-center (2019) September 5. Beedholm-Ebsen R. Trends in Drug Development – In Denmark and Globally International Pharmaceutical Industry (2018) 10 (2) 6. Sørensen HT, Pedersen L et al. Danish clinical quality databases - an important and untapped resource for clinical research. Clinical Epidemiology (2016) October (8) 7. Kinkorová J. Biobanks in the era of personalized medicine. The EPMA Journal (2016) 7 (4)

Rasmus Beedholm-Ebsen

Rasmus Beedholm-Ebsen is Special Advisor within Life Science, at Invest in Denmark, under the Ministry of Foreign Affairs of Denmark. Rasmus received his PhD in Medicine at Aarhus University, Denmark and worked as a post-doc at the Department of Medical Biochemistry at Aarhus University before joining Invest in Denmark. Recently Rasmus received a Bachelor of Commerce degree and he holds a MBA. Besides, Rasmus is Scientific Expert Reviewer for the European Commission.

Email: rasbee@um.dk