GlaxoSmithKline (GSK) encountered this problem with Benlysta (belimumab), which received EU marketing authorisation for systemic
lupus erythematosus in July 2011. Upon assessment, the G-BA stated that the appropriate comparator therapy in the GSK dossier
should have been an optimised standard therapy with various drugs that had been approved in Germany. They criticised the two
main clinical studies in the dossier as having inappropriately restricted the possibilities for adapting the standard therapy,
even though these studies had been acceptable for EMA regulatory approval. As a result, the G-BA concluded that added benefit
had not been proven for Benlysta, which provoked a furious reaction from GSK. The company reportedly called the decision “inexplicable
from a medical point of view” (1). GSK is now faced with a situation where a discount to Benlysta’s price in Germany may be
forced upon them. To add to GSK’s woes, the UK’s cost–benefit assessment agency, the National Institute for Health and Clinical
Excellence (NICE), also rejected the drug, which does not bode well for Benlysta’s commercial success in the European market
as a whole.
Biogen’s multiple sclerosis drug Famypra (fampridine), which gained EU marketing authorisation in July 2011 had a slightly
different issue with the G-BA. The body had specified physiotherapy as being the appropriate comparator therapy for the benefit
assessment, but Biogen presented data on an indirect comparison (2). While it is technically acceptable to use an indirect
comparison, the G-BA was critical of Biogen’s methodology. In addition, they remarked that the studies on physiotherapy included
patients with a markedly lower grade of disability than patients in the Fampyra studies, and concluded that there was no proof
of added benefit for the drug.
Despite the unpopularity of the G-BA’s views regarding comparators, pharmaceutical companies have been unable, to date, to
overturn the negative decisions. However, the G-BA ran into problems when it directed IQWiG to assess InterMune’s Esbriet
(pirfenidone), which had been approved as an orphan drug for mild to moderate idiopathic pulmonary fibrosis (IPF). The approval
process for orphan drugs involves determining added medical value with respect to current treatments. When IQWiG concluded
that there was no additional benefit of Esbriet in IPF, the company criticised the body for having overstepped its mandate
because orphan drugs are exempt from their assessment (3). IQWiG disputed this opinion, stating that orphan drugs also required
a dossier and that while such drugs may be approved on the basis of providing benefit, their role would be to establish the
extent of the added benefit (4). However, under heavy pressure from pharmaceutical industry associations, physicians and patients,
the G-BA, as final decision maker, relented and granted the additional benefit of Esbriet. InterMune will now enter price
negotiations in Germany.
Another orphan drug that has squeezed through the system in 2012 was Pfizer’s Vyndaqel (tafamidis meglumine) for the treatment
of transthyretin amyloidosis. Although stating that some statistically significant advantages or disadvantages of Vyndaqel
compared with the comparator treatment were lacking in the company’s submitted dossier, IQWiG grudgingly described the drug
as providing a “hint of a positive effect” on the disease (5). This was backed by the G-BA, meaning that Pfizer could progress
to the pricing negotiations stage.
Complaints but compromise?
Based on the general problems that companies have run into with IQWiG and the G-BA during 2012, the pharmaceutical industry
continues to be suspicious about the assessment process. In particular, the outcome of the next assessment for Trajenta will
be important. Recently, the European Federation of Pharmaceutical Industry Associations (EFPIA) supported the German pharmaceutical
industry association, the VFA, in calling on the German government for urgent action regarding the new pricing system (6).
The industry associations complained that the rigid German system would force companies to delay launching their drugs in
the German market, and that patients would lose out as a result. Furthermore, companies would have less of an incentive to
invest in the German market.