High cost medicines how to make them affordable Finnish perspective

Transcription

1 Rational use of medicines within the social and healthcare system: effective use of research data August 21, 2018 High cost medicines how to make them affordable Finnish perspective Heikki Ruskoaho Division of Pharmacology and Pharmacotherapy Faculty of Pharmacy 1

2 Current trends in pharmacotherapy The importance of pharmacotherapy increases in health and medical care The potential for drug treatment increases in diseases in which they are not yet effective (e.g. due to rare diseases research and drug development) The definition of a drug changes novel biological drugs agents influencing genes and protein production gene and cell therapy tissue engineering drug-device combinations Growing number of novel drugs New mechanisms of action Distinct safety issues Personalized, individualized pharmacotherapy Cost-effectiveness of pharmacotherapy

3 FDA approved drug products NME, small molecules,; BLA, biologicals Sales 2016 Mullard A. Nature Rev Drug Discov February 2017;16:73-76

4 The scheme focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These medicines are considered priority medicines by EMA. To be accepted for PRIME, a medicine has to show its potential to benefit patients with unmet medical needs based on early clinical data. EMA offers early and proactive support to medicine developers to optimize the generation of robust data on a medicine s benefits and risks and enable accelerated assessment of medicines applications.

5 FDA- Breakthrough Therapies Breakthrough Therapy Designation. A breakthrough therapy is a drug: intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If a drug is designated as breakthrough therapy, FDA will expedite the development and review of such drug.

6 PRIME (EMA) and Breakthrough Therapy Designation (BTD, FDA) candidates by therapeutic area Mullard A. Nature Rev Drug Discov February 2017;16:

7 Orphan drugs EMA Orphan Designation: it must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; the prevalence of the condition in the EU must not be more than 5 in 10,000 or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development; no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. About 30 million people living in the European Union (EU) suffer from a rare disease

8 Analysis of orphan designations in the European Union Morel et al. Nature Rev Drug Discover 2016;15;375

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10 2017: A year of FDA firsts in rare diseases Tisagenlecleucel First gene therapy approval in the United States Avelumab First FDA-approved treatment for metastatic merkel cell carcinoma Lesipasvir + sofosbuvir First HCV direct-acting antivirals appoved for use in adolescnts Celiponase alpha First FDA-approved treatment for a form of Batten disease Edaravone First new treatment for patients with ALS over 2 decades Ibrutinib First FDA-approved therapy for the treatment of chronic graft-versus-host disease (GVHD) Benzidazole First treatment approved for the treatment of Chagas disease

11 Availability and affordability of medicines There is little value in new drugs that patients cannot afford There is no value in drugs that do not exist Improving patient access to effective and affordable medicines is an imperative for public health, social equity, and economic development A number of policy changes suggested to make drugs affordable to patients who need them From direct controls or setting limits on drug prices to recommendations on transparency, research and development

12 Availability and affordability of cancer medicines* Policy and economic objectives Off-label prescribing Price regulation and procurement Pricing policies in countries Controlling costs Differential pricing Managed entry agreements Cross-border collaboration Generic medicines Transcparency Research and development costs Pediatric oncology Balancing public health and industry needs Voluntary licensing and TRIPS (Traderelated aspects of Intellectual Property Rights) Patient access initiatives Competition *WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

13 Availability and affordability of cancer medicines Strengthening pricing policies at the national and regional levels Improving the consistency of policies across health and other sectors Designing of differential pricing sensitive to health systems ability to pay Enhancing system ability to review and adjust prices, and divest if required Creating competition among substitutable cancer medicines, with respect to price, quality and supply WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

14 Availability and affordability of cancer medicines Improving the efficiency of expenditure on cancer medicines Prioritizing the selection of medicines with high(er) clinical value with reference to existing guidance and country context Considering the costs of the model of care as part of the pricing approach Considering managed entry agreements for expenditure control in specific cases such as medicines with anticipated high expenditure and uncertain longer-term clinical benefits Avoiding the use or establishment of funds earmarked for the provision of cancer medicines, unless such funds are essential for access to medicines with proven clinical and economic value Implementing pre-authorization as a measure to ensure appropriate use WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

15 Availability and affordability of cancer medicines Improving the transparency of pricing approaches and prices of cancer medicines Disclosing the net transaction prices of cancer medicines to relevant stakeholders Disclosing and controlling prices along the supply chain Reporting the cost of research, development and production, including any public sources of funding Communicating pricing and reimbursement decisions to the public, when appropriate, to foster a common understanding and promote accountability WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

16 Availability and affordability of cancer medicines Promoting cross-sector and cross-border collaboration for information sharing, regulation, and procurement Sharing information on medicine prices and technical assessments Harmonizing regulatory requirements for biosimilar medicines to ensure safety and quality, and to promore competition Streamlining cross-border regulatory requirements and supply management of medicines in shortage Pooling sub-national, national and regional resources for joint negotiation and procurement Applying TRIPS flexibilities for patented medicines where appropriate WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

17 Availability and affordability of cancer medicines Managing factors that would influence demand for medicines Removing financial/non-financial incentives for prescribing cancer medicines with limited clinical value Restricting promoting activities of cancer medicines to clinicians and the public Correcting any misperception of inferior quality of generic or biosimilar medicines Implementing regulatory measures upon identification of substandard and falsified medicines WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

18 Availability and affordability of cancer medicines Realignment of incentives for research and development Incentivizing research for cancer that affect smaller populations Focusing on health service research to improve system efficiences, rational use of medicines and packages of care WHO: Informal Advisory Group on the availability and affordability of cancer medicines Report of the meeting 4-6 April 2018, Geneva, Switzerland

19 Development of the medicine reimbursement system* 1. Development of medicine reimbursement system based on the current system Clarification of the system (categories of compensation, their level and content and how they will be looked at in the future) The scope of the compensation system (conditions for reimbursement) 2. Developmental needs of the medicine reimbursement system in a changing operating environment and interfaces Considering the SOTEreform (e.g. simplifying multi-channel funding) Renewed marketing authorization procedure (possible novel operating models of the EMA) New and expensive medicines Orphan drugs Rational use of medicines (e.g. non-drug treatment options) 3. An estimate of possible medicine reimbursement measures to limit drug costs *Reports and memos of the Ministry of Social Affairs and Health, 20/2018

20 Key figures for medicine sales and their reimbursement in year 2016 million Total sales of pharmaceuticals Prescription medicines in outpatient care OTC medicines in outpatient care 352 Sales in hospitals 578 Reimbursement of medicine costs Basic Refunds 316 Special Refunds 942 Additional Refunds 154 Finnish Statistics on Medicines 2017 Finnish Medicines Agency Fimea & Social Insurance Institute (Kela)

21 Medicine reimbursements during years millions Milj. euroa (vuoden 2017 rahana) Peruskorvatut Basic lääkkeet Refunds (40(40%) Erityiskorvatut Special lääkkeet Refunds (65(65%) Erityiskorvatut Special lääkkeet Refunds (100(100%) Lääkkeiden Additional lisäkorvaukset Refunds Kela

22 Current medicine reimbursement system The disease-based system controls the cost of compensation and the number of medicines in many ways The system has in particular supported the drug treatments of the diseases of the general public or diseases, which cause significant patient-specific costs Restrictions of reimbursement (Restricted Basic and Special Refunds) has made it possible to include expensive medicines in the reimbursement system Most of the compensation events are easy for both the patient and the health insurance system

23 Objectives of the medicine reimbursement system Drug treatment according to best practices for all those in need In particular, safeguards the use of medicines of people with low income and using many drugs Encourages the use of cheaper products Allows the inclusion of new innovative (often highcost) medicines into the reimbursement system

24 Assessment of therapeutic value of medicines Overall medical and health economic assessment The quality of the illness, the necessity and economy of the drug as well as the therapeutic value demonstrated in the clinical studies and the use Drug efficacy compared to comparator products Safety of drug versus comparator The drug's economy compared to the comparator and/or other treatments Severity of the illness (severe, long-term) The requirement of medicines Replacement or curative action Evaluation of the therapeutic value and need of medicines relative to the costs incurred compared to the benefits and costs of similar therapies

25 Assessment of therapeutic value A uniform national assessment of the therapeutic value of medicines and the cost-effectiveness assessment should be made comprehensively at national level for all medicinal products, irrespective of the pharmaceutical form (oral dosage, intravenous administration) A special justification for this is the equal opportunity for patients to have an effective, safe, affordable and innovative medicines

26 Hospital drugs They are not subject to the authority's reimbursement and/or price regulation The regulation of the prices of pharmaceuticals will be implemented through the procurement process The procurement process does not have a direct connection with the therapeutic and economic evaluation Hospital districts or special areas of responsibility will each decide to include a new drug Policies may vary in different areas

27 Evaluation of therapeutic value of medicinal products Application Assessment of the therapeutic value Outpatient care drugs Expert group Board Secreteriat Hospital drugs Expert group Kela Outpatient drugs Implementation Erva/Sote districts Hospital drugs

28 Medicine Agency It would be appropriate to combine the evaluation and decision-making of the therapeutic value of both the outpatient prescription drugs and the hospital medicides into a single unit (the Board) The natural site of the Board would be under Fimea, which could be turned into a medicine agency (Finnish Medicine Agency, FMA)

29 Kela s execution system Kela would continue to make decisions on the prerequisites for reimbursement rights and the rights of customers for reimbursement on the basis of decisions of the Pharmaceuticals Pricing Board Both the medical reimbursement system and the Kela s implementation system should be developed to better take into account medical treatment in accordance with good practice, special therapeutic grounds and individual medical treatment needs to reduce patient inequality

30 Individualized cancer drug therapy New anticancer drugs are more often oral dosage formulations In the case of mutation-based treatments, oral drug treatment according to best practice is not always reimbursed Inequality between common cancers and rare cancers Inequality in the use of medicines in the hospital for intravenous and outpatient oral dosage medicines Moreover, income support can be granted for a corresponding outpatient cancer drug, which also results in inequalities between patients

31 Drug sensitivity testing in personalized cancer treatment Diagnosis Testing drug efficacy Individualized selection of the drug for the patient Monitoring efficacy and safety

32 Individualized mutation-based leukemia pharmacotherapy Chronic myeloid leukemia therapy has developed rapidly in recent years The diagnosis is based on the detection of a Philadelphia chromosome (Ph) or fusion gene (BCR-ABL1) from a bone marrow and/or blood sample First-line treatment with tyrosine kinase inhibitors imatinib and nilotinib In the second line, dasatinib, bosutinib and ponatinib Some patients develop complete resistance to all of the aforementioned drugs due to Thr315Ile mutation Axitinib is used to treat renal cancer, but is also effective in the treatment of chronic myeloid leukemia if a patient has the BCR-ABL1 gene Thr315Ile mutation* Axitinib is not reimbursed for chronic myeloid leukemia *Pemovska et al.,nature 2016

33 Individualized pharmacotherapy and special therapeutic grounds Possibility for Kela in special situations on medical grounds, in severe and longterm illnesses, to make separate decisions on medicines The product should be in a medical reimbursement system The right to reimbursement is granted on the basis of a review of the medical report on a specialist medical care unit in a multidisciplinary expert group, and will be consulted, where appropriate, of a network of medical specialists in the field of decision-making Diagnosis is required to be based on diagnostic criteria in accordance with good national and international therapeutic recommendations In the medical report, in addition to the information on the disease and its previous treatment and treatment results, the medical report must include a management plan in accordance with good therapeutic practice, based on the scientific research The right to reimbursement is granted on a temporary basis for the period required for an appropriate management plan

34 Managed entry agreements The conditional reimbursement model should be regularized and introduced as a controlled inclusion of particularly expensive and innovative medicines also in hospitals The model of conditional reimbursement would also provide an opportunity for the national assessment work, the inclusion and acquisition of reimbursement of rare diseases, and thus to ensure equality between regions

35 Special refunds Consideration should be given to the transfer of some serious and long-term illnesses from lower (65%) to the upper special refund category (100%) as compared to other illnesses of upper special refund category The conditions for reimbursement should be updated in line with changing pharmacotherapy and good medical practice Kela's specialists should monitor and update the classification of illnesses as drug therapy develops

36 Pulmonary hypertension Pulmonary hypertension is a rare illness. The number of new cases is estimated to be 5-10 per million inhabitants per year. Patients' prognosis is poor, as about 15% of patients today will die in the first year. Some patients are suitable for lung transplantation. Idiopathic pulmonary hypertension (unknown cause) is a rare form of pulmonary hypertension reported annually by one or two Finns, most of whom are years old and 70% are women. There are several drugs available (sildenafil, tadalafil, ambrisentan, bosentan), and in most cases multiple medicines are used simultaneously Pharmacotherapy improves the patient's performance and probably also a prognosis Lifestyle or other means cannot influence the onset of pulmonary hypertension

37 Some changes in the Finnish medical reimbursement system Partially (50%) and completely reimbursable (100%) medicines, 27 illnesses (1964) diseases in the system New reimbursement category, lower special refunds (90%) 1986 This category included hypertension, heart failure, rheumatoid arthritis, bronchial asthma and chronic urinary tract infection New coronary artery disease, arrhythmia, ulcerative colitis and Crohn's disease Malignant tumors, whose treatment was reimbursed earlier by 50%, were fully reimbursed (100%) Lower special refunds 1994, 80%> 75% Gout and connective tissue diseases were moved into this category from higher category (100%) Chronic urinary tract infection were moved to basic refunds (40%) Restricted refunds for medicinal products 1998 This included, among others, certain medicines for MS, erectile dysfunction and obesity Narcolepsy was included into the lower special refunds category (72%) Lower Special Refunds (65%) 2017 Oral anti-diabetic drugs were moved into this category

38 Funding In the case of financing, the state's share (67%) in the financing of medical reimbursements in the context of the reform of the social and health care system should be transferred to the responsible region/county Regions/counties would have then an incentive to manage medication costs and control the prescribing of medicines (low-cost preparations, products in reference pricing system and biosimilars) in their regions cost-effectively, while increasing simultaneously the cost-awareness of drug prescribers

39 Promoting safe and effective biosimilars can lead to biologic medicine affordability Biosimilar entry led to an average decrease in the cost of therapy from 17% in the HGH market to 39% in the G-CSF market throughout the EU 10% 0% -10% -20% HGH EPO G-CSF -17% -9% -9% -12% -16% -14% -25% -22% -25% -36% -39% -33% 6% -28% -19% -22% -40% -30% -55% -40% -50% EU Average UK France Italy Germany Spain 2013 Cost of Therapy Compared to 2006 Note: Countries included: Austria, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, UK. HGH = Human Growth Hormone (somatropin), EPO = Erythropoietin, G- CSF = Granulocyte Colony-Stimulating Factor. Source: Health Advances analysis; IMS Institute for Healthcare Informatics 2014 Assessing biosimilar uptake and competition in European markets.

40 Healthcare systems can utilise savings through the use of generic medicines Generics Share of the Total Pharmaceutical Market, 2014 US Germany Mexico Korea Canada UK Australia Japan Turkey France Italy 87% 79% 77% 75% 75% 74% 66% 66% 64% 62% 55% Potential for cost savings through generic utilization 0% 20% 40% 60% 80% 100% Source: Health Advances analysis; IMS MIDAS audited data.

41 Drug prescription Along with the development of the medicine reimbursement system, controlling prescribing should be developed nationwide and regionally into cost-effective direction The implementation of pharmacotherapy in accordance with the best medical practices should be monitored by means of indicators In order to influence the drug prescribing practices, the feedback system needs to be further developed

42 Guiding drug prescription Ministry of Social Affairs and Health Medicine Agency Erva-regions Advisory board Counties Working committee Prescriber of medicines

43 Rational drug prescription National/regional selection of basic medicines Follow-up of drug prescribing Prescription quotas Education and information tools Guidance on drug prescription Use of generic names for medicines in prescriptions Financial incentives for drug prescribers Budget goals Kiviluoto 2016 Research Strategy for Rational Pharmacotherapy Reports and Memorandums of the Ministry of Social Affairs and Health 25/2018

44 High cost medicines how to make them affordable The goal of pharmaceutical services is to enable effective, safe and costeffective pharmacotherapy The development of the medicine reimbursement and implementation systems should take into account the changed and high-cost medical treatment The potential for drug treatment increases in diseases in which they are not yet effective New drugs on the market are increasingly being used for smaller groups of patients or for the treatment of rare diseases Accelerated marketing authorization procedures with more limited evidence of therapeutic value and cost-effectiveness Individualized, personalized drug treatment, special therapeutic grounds

45 Proposals All medicines should undergo a nationally harmonised and comprehensive assessment of their therapeutic value and cost-effectiveness at the national level, regardless of the type of medication The therapeutic value assessment of outpatient prescription and hospital drugs and related decision-making should be combined into a single unit, under a medicine agency The conditional reimbursement model should be regularized and introduced as a controlled inclusion of particularly expensive and innovative medicines also in hospitals The medicine reimbursement scheme and Kela execution system should be developed to recognise special treatment-related grounds and individual pharmacotherapy needs As regards of funding, the state s share of the funding for the medicine reimbursement scheme should be transferred to the county responsible for payment to provide counties the incentive to steer the prescription of medicines in rationally and cost-effective manner