Basics
In the European Union, around 30 million people suffer from rare diseases. The EU defines a rare disease as a disease which affects less than one person in every 2,000 people. Because expected sales for drugs to treat rare diseases are small, there is little incentive for drug companies to develop new therapies to diagnose and treat such disorders. In 1999 the EU unanimously passed the Orphan Medicinal Products Regulation, to encourage industry to develop therapies for rare conditions by giving financial incentives. Orphan drugs are drugs developed for diagnosing and treating rare diseases. In the current system, drug candidates are designated as “orphan” and market authorised through a centralised European procedure. Availability and reimbursement remain a national responsibility. Although orphan drugs can improve health for millions of people, their high development costs, a small market and marketing exclusivity mean that tend to be very expensive for the patients and health care systems.
The case of orphan drugs raises important issues such as
- How can you put price limits on human life?
- How can treatments for such rare diseases be properly evaluated?
- Is it fair that individuals with a rare disease have more money spent on them per unit of health gain than patients with similar health problems arising from more common diseases?
- Should companies producing orphan drugs keep all their current benefits?
Info cards
- market exclusivity for 10 years from authorisation time(no competitor product can be authorised during these 10 years, unless proven superior),
- financial incentives (fees reduction , free advice on development )
-Priority to EU research programmes
- national incentives in Member States (tax reductions).
During 2000 - 2009, the Committee for Orphan Medical Products received 873 orphan drug designation applications. 598 gained positive opinion. 60 received market authorisation (official approval for use). There are 7000 rare diseases, most do not benefit from a specific medicine.
The main factor that determines access to an orphan drug is the reimbursement by national health insurance systems. The annual cost of these treatments (€ 6000 to € 300 000) is beyond the budget of average households.
The Orphan Drug Regulation (since 1999) has resulted not only in more jobs in the EU but also in increase in Research & Development.
The incentives under the current regulation - market exclusivity, protocol assistance etc - have made it possible for small enterprises to develop new drugs. 1/3 of companies creating orphan drugs are “startups”.
National or regional governments will decide on the assessment of the therapeutic value of the drug, whether to add it to the reimbursement list, its price, its availability in hospitals.
Orphan drugs are often expensive to produce and, by definition, will benefit only small numbers, therefore their price is often really high in order to compensate company’s costs.
The National Institute of Health and Clinical Excellence has suggested that the health care system pays premium prices for orphan drugs based on: severity of the disease, evidence of health gain, whether the disease is life threatening. These criteria vary across Europe.
A survey of haemophilia patients (a rare disease) in the Netherlands showed that treated patients were working 17 years more in 2001 than in 1972. Cost of hospitalisation where treatment is denied can reach €100,000 per year.
Some companies do not provide their marketing approved products in all Member States due to the constraints of pricing (e.g. different taxation laws), reimbursement (delays in some countries) and small return on investments for the company
The cost of orphan drugs is not a major concern today for the member states (they make up one percent or less of most nations’ pharmaceutical budgets)...
Development costs for orphan drugs are substantial, although a little lower than overall costs of mainstream pharmaceuticals (clinical development programmes involve smaller patient numbers).
2/3 of the rare diseases are serious, chronic, and often life- threatening. Characteristics include early appearance; chronic pain; motor or intellectual deficiency, and early death in many cases. Creating therapies for all these is a real unmet need.
In the UK for every £30,000 spent prescribing an orphan drug, the benefit for patients must add up to the equivalent of one patient living a year of good-quality life. Other countries also reimburse based on this method, but have different thresholds.
In many orphan cases there is no “second chance” to conduct an additional clinical study if the available data prove inadequate because there are not enough patients
In some countries a proportion of licensed orphan drugs never reach the patients because they are too expensive
the cost per patient associated with some orphan drugs, can be as high as €500,000 per year and involve treatment for a lifetime
In a family where a child has a rare disease, often one of the parents either stops or significantly reduces work. As a consequence, while expenses increase; income is reduced.
Current EU regulation leaves to Member States the practical implementations on orphan drugs resulting in a lack of harmonisation even across the countries themselves. Some EU citizens may have access to a given drug, whilst others don’t, depending on where they live.
Once the marketing authorisation is granted, the legal delay for placing medicinal products on the EU market is 180 days. However, the average delay is 189 days at the moment, and in some Member states is up to 700 days.
The process from the discovery of a new molecule to the orphan drug marketing for a company is long (average 10 years), expensive (tens of millions of euros) and very uncertain (among ten molecules tested, only one may have a therapeutic effect).
Research on rare diseases has been fundamental to the identification of most human genes identified so far and to a quarter of the innovative medicinal products that received market approval in the EU
As experts on rare diseases are also rare, the authorisation of orphan drugs is almost always made at the European level to benefit from the greatest amount of expertise available.
The procedure for marketing authorisation must be less than 210 days
Some orphan drugs are eventually found to be beneficial for common disorders, (epoetin-alpha, originally approved to treat anaemia is now used in patients undergoing cancer chemotherapy)
The decision to authorise a product is based on balancing its efficacy, its risks, and its quality. If it is highly efficient but potentially dangerous, marketing may be refused. The marketing authorisation, is not based on economic grounds.
The decision to reimburse is the response to the following question: can society afford to pay for this treatment? Is it worth it? The reimbursement decision is based on economic grounds.
Issue cards
How can you keep costs low and make drugs available for patients while giving incentives for companies to stimulate research and make more and better orphan drugs?
Isn’t there an opposition between collective choices and individual preferences? Is it right to spend many resources for few people? Is there a moral obligation of society not to abandon individuals?
The health care system alone? Is responsibility shared with the patient? Or it is to be shared with the marketing authorisation holder in case the product is not as effective as initially thought?
Should patients suffering from rare conditions be entitled to the same quality of treatment as other patients?
Special measures are in place to support research and development of orphan drugs at EU level. Should a similar status be dedicated in decisions about allocating resources for reimbursement at a national level?
EU states that all patients should have equal access to quality of care. If we aim to maximise health outcomes, shouldn’t the cost effectiveness of orphan drugs be the same as for other technologies?
It is the attempt to help someone in danger, no matter the costs. Shall we apply this rule when it comes to rescue the life of someone with a rare and life threatening disease?
When a rare diseases receives an orphan drug, think about the money the state saves in terms of less days of hospital care, no cost of disabilities, less days of work lost by the patient, and tax returns on the industry’s profits
Few additional drugs are predicted to enter the market over the next 10 years. 85 to105 additional drugs are predicted, depending on the rate of drug discovery, time taken to develop them, and success in marketing authorisation.
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In Europe, most health care systems are based on the solidarity principle: the wealthier sharing the burden of diseases by paying more to health insurance. Couldn’t this apply to the use of treatments for life-threatening orphan drugs?
To be reimbursed by a healthcare system a drug needs to be safe, effective, and a cost effective use of public resources. Should drugs for rare diseases be expected to generate sufficient sales to recoup these or should they be subsidised centrally?
Large differences exist between Member States. Hospital orphan drugs are funded at a local hospitals level in some countries with no guarantee for the drugs to reach the patients
If a drug is not cost-effective, can funding of it be justified if the public is willing to give up some of the overall health gain produced by the health care system?
In making decisions regarding ethical dilemmas this approach tries to bring the greatest good to the greatest number of people’. Does investing vast resources for rare conditions, go against this principle?
Article 2 of the European Convention of human rights protects the right of every person to their life
Clinical evidence on ultra-orphan drugs is often based on short-term outcomes rather than long-term effectiveness, and the relationship between the two may not be proven. In this case, how can the utility of these drugs be proved?
Central mechanisms designed to evaluate drugs will encourage bringing medicines that benefit the patients, give early access, allow choice and efficient healthcare.
Even when drugs exist they may still not be available to patients. Successful access to these drugs often only comes following political pressure, legal challenges and persistent advocacy. What happens to patients who cannot fight because they are too sick?
In a society such as ours in which finite resources cannot meet all needs, doesn’t money spent on one service mean money can’t be spent on another?
For some patients the amount spent on home-help services could have bigger impact on their quality of life than spending it on orphan drugs. Shall we make this a bigger priority?
Disease-modifying therapies, unlike best supportive care, offer the option of future knowledge, which may in turn, lead to a cure or at least prevent the disease from worsening
Most rare diseases do not have specific approved treatments. Many are treated “off-label”, using products for other diseases. Health insurance often refuses to cover off-label uses since they are being used in a way that is not approved
Think about how market exclusivity may have excluded potential treatments and companies with competitive prices from coming into the market...
Drug companies can "salami slice" a disease any way they choose to obtain orphan drug designation for drugs with large market
In the spirit of solidarity among Member states, the cost of a drug should be decided according to the wealth of each country. Higher price in wealthier countries would allow more affordable prices in less wealthy countries, as it is done for AIDS drugs
Story cards
Policies
Since resources are limited, there should be a limit and only cost effective drugs that benefit the greater number of patients should be reimbursed. If a drug purchaser has to choose between treating 10 patients with drug A or 1 with drug B for a rare disease, then the choice should always be to treat 10 with drug A.
Only cost effective drugs should be reimbursed, but the approach for orphan drugs should be different than for common diseases. If there is any doubt about the cost effectiveness of an orphan drug, it should be exceptionally reimbursed in certain cases.
Like position 2, but if there is any doubt about the cost effectiveness of an orphan drug, the benefit of doubt should be given to the patient and the drug should be reimbursed systematically.
Health is a priority for European citizens. Just as efforts to rescue people after an accident are not restricted, efforts to rescue a patient with a rare disease should not be limited. Cost effectiveness should not be the parameter on which to base reimbursement decisions.
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