The Expiry of Humira® Market Exclusivity and the Entry of Adalimumab Biosimilars in Europe: An Overview of Pricing and National Policy Measures

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry. Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures. Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab. Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures. Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

The general level of co-payment varies from 10% to 100% for the ambulatory care and hospital lists. Humira ® is present in the hospital list and is reimbursed for patients up to 68% (approximately €108 patient copayment).

Austria
Healthcare in Austria is based on a social insurance model. The Austrian Social Insurance (Dachverband der österreichischen Sozialversicherung, DVSV) is the umbrella organization of the three main sickness funds and two further social insurance institutions. About 99.9% of Austria's population are covered by statutory social health insurance, mainly organized according to regional employment affiliation and vocational groups; there is no free choice of the sickness fund. The system is characterized by income-related health insurance contributions, benefits in kind, direct access to primary, secondary and tertiary care, with co-payments at all levels of care.
The purchasing of medicines in the hospital setting is organized in a decentralized way, with decisions taken by the individual hospital owner organizations.
In ambulatory care, medicines are granted in kind to the insured (e.g., for Humira ® ). There is only a single fixed prescription fee per item. This is currently €6.10 (except when the pharmacy price is lower), and is adjusted yearly. The co-payment is waived in certain cases: 1) If the medicine is for an officially recognized communicable disease, 2) If the patient is exempt, due to low income, or people with low income who have extraordinarily high expenses due to sickness or disability, 3) Persons who have already paid more than 2% of their yearly net income (at least 37 fees) are automatically exempt from the co-payment prescription fee.
In the hospital setting medicines are distributed there without further copayment.

Country
Financing Co-payment Belgium Medicines in Belgium are financed via taxes, compulsory health insurance (via a sickness fund of choice), and patient co-payments.
In ambulatory care, including ambulant patients in the hospital, copayment varies from 0% to 100% based on different reimbursement categories. Co-payment for Humira ® and its biosimilars is limited to €12.10 per package.
In the hospital setting, the use of medicines is included in a lump sum payment.

Bulgaria
In In the hospital setting, (Annex II of the Positive Drug List), the percentage of reimbursement is 100%.
Biological medicines are included in Annex I, but based on the preferences of the company, they could also apply for Annex II.

Croatia
Medicines are financed via health insurance contributions (major part) and general taxes.
In ambulatory care, co-payment of prescription medicines is determined through therapeutic reference pricing (around 60 clusters, most at ATC 4 and 5 levels) and a fee per prescription of circa €1.5.
No co-payments exist for hospital care medicines (including adalimumab and other biological medicines).

Cyprus
This information was not reported. This information was not reported.

Denmark
Medicines are financed via taxes. The government pays for medicines in the ambulatory care setting and the regions pay for medicines in the hospital setting.
In ambulatory care, co-payment exists. In the hospital setting (e.g., adalimumab and other expensive medicines), medicines are free for the patient.

Estonia
Medicines are financed from the social security tax based on solidarity. There is one payer in Estoniathe Estonian Health Insurance Fund. Adalimumab is financed by the Estonian Health Insurance and is delivered via hospital pharmacies as a part of healthcare service. From July 2019 it is also dispensed in general pharmacies as a regular reimbursed medicine.
In ambulatory care, there are three different levels of reimbursement -50%, 75% (90% for the elderly) and 100%. The diseases are classified in different reimbursement categories based on severity. Patients have to pay a €2.50 prescription fee and the remainder of the price of the medicine according to the reimbursement level (0% co-payment for adalimumab). If the patient prefers a product that is more expensive than the current cheapest one, the patient has to pay the extra cost out of pocket.
In hospital care there is no co-payment. In the hospital setting, no separate fee is charged on medicines. A patient only pays a client fee for the interventions during the hospital stay.

Country
Medicines administered during the visit are included in this fee.

Germany
Medicines are financed via statutory health insurance for circa 90% of the population; others are privately insured and/or have state benefits (e.g., soldiers, police, and jail inmates).
In ambulatory care, a co-payment exists of 10% of the retail price (minimum €5 to maximum €10). Exemptions apply for children below 12 (longer under certain conditions) and for low-income groups. This pertains to all reimbursable medicines. Co-payment for originator and biosimilar adalimumab is €10.
In the hospital setting, co-payment is based on the length of stay, but not on the medicine use.

Greece
Medicines are financed via health insurance contributions. For special categories of diseases and medicines, including high-cost medicines and biological medicines such as adalimumab, there is no copayment when dispensed via public pharmacies (hospital pharmacies,

Country
Financing Co-payment EOPYY-pharmacies). The average co-payment for medicines delivered from private pharmacies is 24%, (14.3% standard co-payment and 9.6% additional charges).

Iceland
Medicines are financed via compulsory taxation. In Iceland, medicines are classified in two groups: general medicines and hospital medicines. Adalimumab is classified as a hospital medicine and furthermore, a physician has to apply for its use via the Drug and

Italy
Medicines are financed via compulsory taxation. No co-payments exist for medicines in ambulatory care and hospital setting (e.g., adalimumab). No co-payments exist (if the medicine is in the list and is available, it is free to the patients).

Latvia
Medicines are financed via general taxation in Latvia.
In Latvia the reimbursement is diagnosis based. Based on the character and severity of the disease, medicines are reimbursed at 100% (e.g., adalimumab), 75% or 50% rate of the (reference) price.
The patient has to co-pay when the medicine is reimbursed at 75% or 50% rate, and also when not the reference (cheapest) product is prescribed, the patient pays the difference between the reimbursement sum and the price of the product, for example in the case of Humira ® (but co-payment is insubstantial after an additional discount offered by AbbVie).

Lithuania
Medicines are financed via health insurance contributions.
In ambulatory care, all medicines are 100% reimbursed, but all medicines have a minimum co-payment (not higher than 20% of the reimbursement price for medicines with a retail price less than €20 and for more expensive medicines patient co-payment is not higher than €4.71, e.g., for originator and biosimilar adalimumab). Co-payment can be covered by the marketing authorization holder via confidential discounts.
Medicines in hospital care are without co-payment.

Country
Financing Co-payment

Malta
The system for public healthcare is financed through taxes and through payment of national insurance. Payment of national insurance is mandatory for all workers. Relatively few people have an additional private health insurance, and the people who have private health insurance will have to pay for the private insurance additionally (over and above) the mandatory national insurance.
The medicines supplied through the national health services are all procured centrally and this stock is distributed to public hospitals and to community pharmacies (for primary care). During central procurement the cheapest available alternative is procured.
Medicines provided through the public healthcare system, such as adalimumab, are accessible totally free of charge for patients who are entitled to free medicines through the public healthcare system.
Entitlement is according to a list of disease conditions as set by law.
A patient is either entitled to free treatment and gets the medicine totally free of charge (provided the medicine is supplied through the national health services and the patient is entitled to the medicine for free) or alternatively the patient has to buy the medicine privately and pay the full price for it. In the Netherlands there is only co-payment for a small proportion of nonessential "luxury" medicines (not good enough for general reimbursement, poor cost-benefit ratio etc.).

Financing Co-payment Norway
In Norway medicines are financed from the state based on state income including taxation. The use of medicines by patients receiving treatment in the hospital is covered by the state through the specialist healthcare, which is owned by 4 regional health authorities (reporting to the Ministry of Health). In ambulatory care, for treatment of chronic conditions, the state (insurance system) will cover the major part of the cost. Private health insurance has a minor role in the Norwegian health care system, which is based on a public model.

Poland
Medicines are financed via health insurance taken from taxation. Medicines used in the hospital and ambulatory care setting are fully reimbursed (up to the reference price). Biological medicines are used only the hospital setting, and are free of charge to patients (even when a more expensive adalimumab is used, the hospital will cover the cost above the reference price). Healthcare providers are receiving remuneration from the National Health Fund. This remuneration is limited to the cheapest one in the limit group.

Romania
Medicines are financed mainly via health insurance contributions, the National Health Insurance House (NHIN) dedicated budget, and partially via the Ministry of Health (only for some products included in Public Health National Programs e.g., medicines for HIV-AIDS and tuberculosis).
In ambulatory care, the reimbursement level varies between 20% and 100% of the reference price, depending on the sub-list. Originator adalimumab had first no co-payment, but this was increased to €106.3 per unit due to a change in reference price after the entry of biosimilars.
However, co-payment can be partially/completely covered by the marketing authorization holder via a patient support program.
In the hospital setting no co-payment of medicines exists.

Russia
Medicines are financed according to compulsory taxation. However, the reimbursement system is changing and moving from compulsory taxation (like it was in the Former Soviet Union) to health insurance. Insurance funds have been already established to collect money from different sources and distribute this directly to medical organizations (hospitals, etc.) or to resellers responsible for providing medicines to medical organizations. The main source of money for those insurance funds is still state budget based on compulsory taxation.
No co-payments exist (no charges for prescription medicines in any hospital or ambulatory care setting in Russia).

Scotland
Medicines are financed via compulsory taxation. No co-payments exist (no charges for prescription medicines in any hospital or ambulatory care setting in Scotland).
There is Scottish government advice for co-payment if a medicine has not been approved by the Scottish Medicines Consortium (SMC) and a request by the Peer Approved Clinical System (PACS) process has also been rejected. If the patient still wishes to use it with the support of a private clinician then co-payment can be used. With biological medicines for autoimmune disorders this has not been necessary as no medicine has been rejected by the SMC.

Serbia
Healthcare ( Biological medicines are on List C, there is no co-payment for medicines on List C, and they are only available in the hospital.

Slovenia
Medicines are financed via National Health Insurance (compulsory).
With the co-insurances, which almost the whole adult population has, there is no co-payment. Co-payment is obligatory only in case of medicines that are priced higher than the reference level (reference pricing system for ATC 5&4). Adalimumab is not included in the internal reference pricing system, hence there is no co-payment.

Spain
Medicines are financed via compulsory taxation. In Spain, several cases have to be differentiated: a) If the patient is admitted to a public hospital, all medication received during admission will be paid by the hospital and the patient will not have to pay any co-payment. b) If the patient is not hospitalized, the doctor will write a prescription that, depending on the type of drug in question (complexity of the treatment, cost, etc.), the patient will have to pick it up either at a hospital pharmacy service (no co-payment, e.g. Humira ® ) or at the community pharmacy (several types of co-payment, depending on the patient's income, whether he is a pensioner of social security and whether it is a chronic treatment). Most of the biological medicines are dispensed in hospital pharmacy services and a small number of them in community pharmacies (e.g., teriparatide, insulin, denosumab etc.).

Country
Financing Co-payment

Srpska
The Republic of Srpska is one of the two constitutive entities in Bosnia and Herzegovina. It has executive and legislative functional responsibilities covering healthcare policies. The authority for providing healthcare is centralized, with the Ministry of Health and Social Welfare responsible for planning, regulation and management functions.
Healthcare (medicines as well) is funded mainly via compulsory health insurance contributions. The Health Insurance Fund of the Republic of Srpska (HIF) provides health insurance coverage for the population, and it operates on the basis of solidarity and mutuality. HIF funds the majority of medicines in the health system via few medicines lists upon which it procures medicines (public procurement). Medicines dispensed in the pharmacy with a prescription (the List of medicines dispensed upon a prescription, so-called 'Positive List') are also funded by the HIF, but are not procured via public procurement, but are included in an internal reference pricing system.
The List of medicines dispensed upon a prescription in ambulatory care consists of a List A and a List B. List A is a basic list of medicines, and medicines are covered 100% up to the reference price level for patients exempt from the co-payment; otherwise, there is a 10% co-payment of the reimbursed reference price combined with the additional co-payment for a product more expensive than the reference price. List B is a complementary list with a mandatory 50% co-payment. Adalimumab is not on the List, i.e., cannot be dispensed in the retail pharmacy upon a prescription.
There is no co-payment for medicines used in hospitals (e.g., adalimumab), including for biological medicines.

Sweden
Financing of medicines in the public healthcare system occurs via taxes. In ambulatory care (e.g., Humira ® ), differential co-payments exist up to 2300 Swedish kronor a year for 2019 (approximately €220), and 2350 Swedish kronor a year in 2020 (approximately €225) for all prescribed medicines in the reimbursement schemefree after that. Children younger than 18 year do not pay any co-payment.