Germany's Federal Joint Committee has published new resolutions on the extent of the added benefit of ophthalmology medicine Eylea in a new indication, and idiopathic pulmonary fibrosis drug Ofev.
IHS Life Sciences perspective | |
Significance | The Federal Joint Committee has recently made public its resolutions on the additional benefits of two medicines – ophthalmology drug Eylea in a new indication, and idiopathic pulmonary fibrosis treatment Ofev. |
Implications | Eylea was judged to show no additional benefit, based on the data submitted, for a fourth time, while orphan drug Ofev was assessed to show a minor additional benefit. |
Outlook | Eylea has undergone price negotiations already for other indications, and therefore is currently not threatened with placement in the reference-pricing system. Ofev is likely to have to undergo a full benefit assessment in the foreseeable future, based on the estimated eligible patient population, and the drug's annual costs of treatment per patient. |
Eylea judged to show no additional benefits in new indication
Germany's Federal Joint Committee (G-BA) published on 3 September its resolutions on the extent of the additional benefit of the Bayer (Germany) and Regeneron (US) ophthalmology medicine Eylea (aflibercept) in the indication of impaired vision due to macular oedema caused by branch retinal vein occlusion.
The G-BA's conclusion on the extent of Eylea's benefit in this indication, and its assessment of the dossier submitted in support of the drug's use in this indication, closely matches that of the German Institute for Quality and Efficiency in Healthcare (IQWiG). It concluded that no additional benefit could be ascertained (see Germany: 18 June 2015: Germany's IQWiG finds Eylea lacks additional benefit in treatment of impaired vision due to macular oedema).
In an uncharacteristically brief justification paper, the G-BA assessed that in the study on which the data in the submitted dossier are based, Eylea was used in a manner that deviated from its approved indication, and the appropriate comparator therapy identified by the G-BA – Lucentis (ranibizumab; Novartis, Switzerland) – was not implemented.
The G-BA stated that it could not identify any study carried out by the producers in which Eylea was directly compared with Lucentis. Instead, the producers had used data from a randomised, controlled trial (the 'VIBRANT' Phase III study) comparing Eylea with grid laser treatment. However, according to the G-BA, this trial was not included in the benefit assessment submitted by the companies, although it was submitted in the dossier to demonstrate the efficacy and safety profile of Eylea. The G-BA added that by the time of the launch of the VIBRANT trial, Lucentis was already approved in a number of countries, and would have been available as a comparator.
The full documentation on the early benefit assessment of Eylea in this indication can be accessed here, in German.
Ofev assessed to show a minor additional benefit in IPF
Also on 3 September, the G-BA published its assessment of the Boehringer Ingelheim drug Ofev (nintedanib) in the treatment of idiopathic pulmonary fibrosis (IPF). As an orphan drug, Ofev was not subject to a full early benefit assessment, involving a dossier evaluation by IQWiG. It would be only if its costs to Germany's statutory health insurance funds exceed EUR50 million (USD55.8 million) over a 12-month period.
The G-BA, tasked only with assessing the extent of the drug's additional benefit based on its approval study, decided that it demonstrated a minor additional benefit. The data assessed by the G-BA came from two randomised, double-blinded, placebo-controlled studies, INPULSIS-1 and INPULSIS-2. The assessment of a minor additional benefit derived mostly from the morbidity data, which was concerned with the time to the first acute exacerbation, or time to the first serious acute exacerbation including serious adverse events. The G-BA identified a statistically significant advantage for Ofev in this endpoint, although because of the uncertainties inherent in the study data, it was assessed to show only a minor additional benefit. Positive reports in terms of quality of life helped the G-BA reach its assessment of a minor additional benefit, although a lack of improvement in terms of mortality meant that nothing more than "minor" status could be awarded.
The full documentation relating to Ofev's assessment by the G-BA can be accessed here, in German.
Outlook and implications
Eylea has already been through three early benefit assessments in other ophthalmological indications, and has not been awarded additional benefit status in any of them. However, the drug has been the subject of price negotiations with the German National Association of Statutory Health Insurance Funds (GKV-Spitzenverband), and has not been included in a reference-pricing group because it could not be placed with a sufficient number of other medicines to form a reference group. The fact that it has been declared to show no additional benefit in this indication, based on the submitted dossier, underlines the methodological emphasis on direct comparison studies and the importance – in many instances - of complying with the G-BA's choice of comparator therapy.
Nintedanib is also marketed by Boehringer as an oncology medicine (under the brand name Vargatef), and has already been assessed to show an additional benefit in adenocarcinoma non-small-cell lung cancer. Its positive assessment by the G-BA is a boost for the company, and the influential status of the German authorities in decisions made in other European countries will also be beneficial. However, considering the expected number of patients eligible for treatment with the drug in Germany – 7,550 – and the annual cost of therapy per patient – EUR41,820.73 – it is likely that the drug would have to undergo a full early benefit assessment sooner rather than later.