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.

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.