Orphan drugs are medicinal products used for the medicinal treatment of rare diseases. The AMNOG (German Act on the Treatment of Rare Diseases) has brought them back into the spotlight of health policy debates, as they are exempt from an early benefit assessment (Section 35a of the German Social Code, Book V). Thus, proof of (additional) benefit only needs to be provided if the statutory health insurance (SHI) revenue of an orphan drug exceeds €50 million in a single year. But how often is this revenue threshold actually exceeded? According to data from INSIGHT Health, all orphan drugs combined generated annual revenue of just under €1 billion.

>> Orphan diseases are diseases that occur very rarely in the population. In Europe, this is defined, among other things, by the fact that no more than 5 in 10,000 people may suffer from them. According to the German Federal Ministry of Education and Research, there are over 7,000 such rare diseases. These diseases are treated, among other things, with drugs known as orphan drugs or orphan medicinal products (i.e., the "orphans" among medicines).
These drugs for the treatment of rare diseases are often of less interest to the pharmaceutical industry due to their small market size and their relatively low sales, coupled with high development costs. Legislators are attempting to counteract this with regulatory levers. In January 2000, the EU enacted the Orphan Medicinal Products Regulation, which aims to promote and develop such drugs. Ten more orphan drugs are expected to be added to the existing 61 approved orphan drugs in 2011 (with a total of 30 new active ingredients expected to be launched in 2011).
What is interesting for non-insiders is that alongside the lesser-known drugs, familiar active ingredient names also appear, such as ibuprofen; this active ingredient, however, is sold under the lesser-known product name "Pedea" for the treatment of patent ductus arteriosus in premature babies, a congenital heart defect.
Orphan drugs with special status
Orphan drugs are also treated separately in the Pharmaceutical Market Restructuring Act (AMNOG), which came into force on January 1, 2011. Thus, for them (unlike other medicinal products), the additional medical benefit is already considered proven by the approval, since – according to the justification for the amendment in Section 35a of the Social Code (SGB V) – "it can generally be assumed that there is no therapeutically equivalent alternative for the treatment of this disease." Only if an orphan drug achieves sales based on pharmacy selling prices (AVP) of more than 50 million euros in the last 12 calendar months must the additional benefit be demonstrated for this medicinal product.
In recent weeks, there has been much discussion about the content and purpose of this exception, which was only included in the final version of the AMNOG (see text box on page 13): The chairman of the Federal Joint Committee (G-BA), Hess, considers the "general statutory assumption of a solitary status with additional benefit" for orphan drugs unsatisfactory, as there are already rare diseases for which several orphan drugs are approved. In this context, "to protect patients, the possibility of a comparative benefit assessment by the G-BA with corresponding conclusions regarding prescribability at the expense of the statutory health insurance must remain possible" (G-BA press release of October 27, 2010).
In their article "Arzneimittelmarktneuordnungsgesetz: Zu guttetzt ist alles selten" (Dtsch Arztebl 2010; 107(42): A-2032), Windeler et al. argue that the special status of orphan drugs is already being deliberately exploited by the pharmaceutical industry. For example, relatively common diseases, such as cancer, are broken down into small subgroups in order to then claim orphan drug status "piece by piece." After approval is granted, a second step (without extending the approval) involves a gradual expansion of indications, which then leads to "off-label use."
These strategies would be further promoted by waiving early benefit assessments for orphan drugs. However, IQWiG head Windeler sees the inclusion of a sales limit in the law as at least a "protection to limit financial abuse" (see Handelsblatt interview with IQWiG head Jürgen Windeler from November 11, 2010). BPI head Wegener, however, finds this sales limit regulation incomprehensible, since the "additional benefit does not depend on the sales of a drug" (BPI press release from November 11, 2010).
“Drug orphans” with more than 50 million euros in sales?
The €50 million sales threshold, above which proof of (additional) benefit must be provided, is also viewed very differently: Some consider it so high that practically no orphan drug falls under this regulation. Others question this, given the sometimes very high treatment costs of rare diseases.
INSIGHT Health has conducted a special analysis on this topic, based, among other things, on a complete record of almost all billed outpatient statutory health insurance prescriptions. The analysis reveals a very heterogeneous picture for existing orphan drugs:
1 billion euros in sales of orphan drugs
The 61 orphan drugs generated combined sales of almost one billion euros in the outpatient statutory health insurance market over the past twelve months. While some drugs were not prescribed at all or only occasionally in the outpatient sector, five drugs generated sales of more than 50 million euros – the sales threshold above which (additional) benefit must be demonstrated for new orphan drugs in the future (see Figure 1).
Three of these five products are approved for more than one rare disease. The product "Glivec," containing the active ingredient imatinib, which has annual sales of over €280 million, even has approvals for six orphan diseases (see www.vfa.de/orphans). It should be noted that the AMNOG regulation only applies to new active ingredients introduced after January 1, 2011. Therefore, this overview can only provide an initial assessment of the likely relevance of this exemption. It should also be considered that the initial approval of three of the five drugs with sales of over €50 million was granted over eight years ago. The topic of orphan drugs will continue to occupy insiders in this "billion-dollar niche" in 2011—also due to the ten new approvals expected.

24,742 euros for one regulation
The pharmacy selling prices (AVP) of the various orphan drug forms currently on the market range from €64.46 to €24,471.56 (as of January 15, 2011). Thus, the prices of orphan drugs are often among the highest in the pharmaceutical market: Among the 30 prescribed medicines with the highest prices (according to the AVP of the most expensive form not reported as off-sale), 18 are products that have orphan drug status (see Table 1).