The German Institute for Quality and Efficiency in Healthcare (IQWiG) has issued the results of its assessments of four drugs, with only one being judged to have an additional benefit.
IHS Global Insight perspective | |
Significance | IQWiG has published the conclusions of its assessments of four drugs (in one case, a new indication of a previously assessed drug) and has decided to accord additional benefit status to only one. |
Implications | As the first four assessments to be published this year, the tone set by IQWiG for 2014 is certainly restrictive. |
Outlook | There remains a chance that those drugs that have not been granted additional benefit status may yet gain such status if the producers submit new material that can sway the G-BA – particularly since IQWiG's negative assessments of the drugs concerned are mainly based on formal considerations. |
Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) has started the new year with the publication of the results of four new assessments of medicines under the Pharmaceutical Market Restructuring Act (AMNOG). The conclusions of the assessments are summarised below.
Tafinlar shows no additional benefit
The GlaxoSmithKline (GSK, UK) drug Tafinlar (dabrafenib) has been assessed in the treatment of inoperable, advanced malignant melanoma for patients with the BRAF V600 mutation. The appropriate comparator therapy that the Federal Joint Committee (G-BA) chose was dacarbazine. The manufacturer had submitted data from a direct study (BREAK-3) with dacarbazine and IQWiG has identified an issue with the fact that, in the study, patients were able to switch from dacarbazine treatment to treatment with Tafinlar. The institute has questioned which of the drugs the recorded effects could be traced back to, in the case of patients who had received both. Regarding overall survival (OS), IQWiG has stated that there were no statistically significant differences between patients treated with dacarbazine and those receiving Tafinlar. The institute has stated that while the manufacturer has made claims regarding progression-free survival (PFS), this is a surrogate endpoint and can only be considered if its relation to the "patient-relevant" endpoint of OS can be demonstrated. According to IQWiG, since this relation was not demonstrated in the dossier, the PFS claim cannot be considered in the assessment. Furthermore, IQWiG has determined that there were no statistically significant differences in health-related quality of life between the two treatment groups and considered data presented on side effects to be uncertain. In summary, IQWiG has decided that Tafinlar lacks an additional benefit in this indication. The IQWiG press release summarising the results of its assessment can be accessed here, in German.
Aubagio not judged to have additional benefit
IQWiG has also recently completed its assessment of Aubagio (terfilunomide), developed by Sanofi (France) subsidiary Genzyme (US), for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS). The G-BA identified beta interferons 1a or 1b, as well as glatiramer acetate, as possible appropriate comparator therapies and the producer has presented data comparing its drug with Rebif (interferon beta-1a; Pfizer, US), which is an injectable treatment, while Aubagio is an oral treatment. IQWiG has noted that while data from a direct comparison between the drugs had been presented, the manufacturer had also provided data from an indirect comparison, in which both Rebif and Aubagio were compared with placebo, which acts as a bridge comparator. The institute has stated that the results of the indirect comparison cannot be considered in support of those from the direct comparison and therefore it only considered the results from the latter. IQWiG has judged that the study was too short and involved too few patients to provide any relevant mortality data. In addition, it has found no statistically significant differences in progression of disability, or in serious adverse events and discontinuation of treatment due to side effects. It has identified some advantages for Aubagio in non-severe side effects, although, even in this case, there were disadvantages identified for the Sanofi drug. Overall, IQWiG has decided that the study on which the data submitted was based lacked reliability, partly because it was not blinded, and it has judged that the drug lacks an additional benefit. The IQWiG summary of its assessment can be accessed here, in German.
Eylea fails to gain additional benefit status on formal considerations
IQWiG has also completed its assessment of the Bayer (Germany) drug Eylea (aflibercept) in the treatment of visual impairment due to macular edema after a central retinal vein occlusion. The G-BA identified as potential comparator therapies Lucentis (ranibizumab; Novartis, Switzerland) and intravitreal implant with dexamethasone. The producer had presented the results of three studies in which Eylea was indirectly compared with Lucentis. IQWiG has stated that in the studies on which the data submitted in the producer's dossier was based, both Eylea and Lucentis were administered in a different manner from that provided for in their approvals. Therefore, it was unable to estimate the extent the results of the studies differed from the results of treatment in accordance with the drugs' approvals and found no additional benefit could be demonstrated from the dossier. The IQWiG's summary of the assessment can be accessed here, in German.
Stivarga judged to have minor additional benefit
IQWiG has also completed its assessment of another Bayer drug, Stivarga (regorafenib), in the treatment of metastatic colorectal cancer. The G-BA identified best supportive care (BSC) as the appropriate comparator therapy and the producer's data was based on a pivotal trial in which one group received Stivarga and BSC while the other received BSC and placebo. Although it has found issues with the study's reliability, IQWiG has judged that the Stivarga treatment demonstrated statistically significant improvements in OS, compared with the comparator. The institute has judged that the data presented on morbidity could not be considered for the assessment, while finding that there were no statistically significant differences in terms of serious adverse events and discontinuation of treatment due to adverse events. Therefore, IQWiG has decided that because it could identify no other significant advantages for treatment with Stivarga apart from a better OS result, its overall assessment was that the drug showed a minor additional benefit – even though the superior OS would tend to indicate a significant additional benefit. The IQWiG's summary of its assessment can be accessed here, in German.
Outlook and implications
In the case of all four drugs, a period now follows in which their producers may submit additional written or spoken material in support of their applications before the G-BA makes its final resolution, within approximately three months.
The three drugs that have not been accorded additional benefit status (in the case of Eylea it has been assessed for a new indication) have mainly failed to do so because of formal reasons. It remains possible that with different data, which are more in line with IQWiG's strict approach, they will end up with a different result. It is also possible that the manufacturers will be able to submit material that convinces the G-BA to diverge from IQWiG's conclusions.
Eylea has recently been recommended for reimbursement by the United Kingdom's National Institute for Health and Care Excellence (NICE) in the same indication, while Tafinlar has received positive reimbursement recommendations in Canada and Australia. NICE has also recently recommended Aubagio in RRMS.
Therefore, the conclusions of these assessments by IQWiG have shown that the German assessment system introduced under the AMNOG law remains a tough regulatory barrier, compared with other markets.