On 4 January 2016, the German Institute for Quality and Efficiency in Healthcare published dossier evaluations of four oncology medicines, giving mixed assessments.
IHS Life Sciences perspective | |
Implications | IQWiG's first published dossier evaluations of the year show mixed fortunes for the four oncology drugs concerned, with the institute's methodological strictness in terms of data quality continuing to prevail. |
Outlook | There remains a chance that in the consultation period, producers could submit additional information that could influence the G-BA's eventual final verdict. |
Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) published dossier evaluations of three oncology medicines on 4 January, the first to be published in 2016.
IQWiG sees minor additional benefit for Stivarga for second time
IQWiG published its second dossier evaluation for the Bayer (Germany) drug Stivarga (regorafenib), in the treatment of adults with metastatic colorectal cancer (mCRC), in patients for whom alternative treatments are no longer effective, or for whom alternative therapies are not appropriate. The re-evaluation was carried out because the Federal Joint Committee (G-BA) had imposed a time restriction on its previous resolution on Stivarga in this indication, which expired in July 2015.
Stivarga was found to show an indication of a minor additional benefit by the G-BA in its first benefit assessment, which was consistent with IQWiG's verdict. IQWiG has reached the same conclusion in this new evaluation. In general, IQWiG saw advantages for patients in terms of overall survival, but certain serious side effects occurred more with Stivarga than with the comparator therapy.
The G-BA again identified best supportive care (BSC) as the appropriate comparator. As IQWiG explained, data from the same clinical studies were used in the second as in the first evaluation. The producer also submitted new analyses regarding symptoms, quality of life, and adverse events. However, IQWiG found faults with the data, emphasising particularly the fact that within the context of BSC, no other systemic anti-tumour medications were used in the studies, and it was not clear whether additional medications could have alleviated symptoms. Furthermore, the exclusion of patients in a worse general condition, with an ECOG performance status of 2 or higher, was highlighted by the regulator. As IQWiG stated, the drug is indicated for the treatment of these patients, and the reasoning behind the G-BA's decision to restrict the duration of its original resolution was partly related to the absence of data on such patients in the first submission.
The full summary of IQWiG's second dossier evaluation of Stivarga can be accessed here, in German.
Imnovid demonstrates no additional benefit, IQWiG decides
IQWiG also published its dossier evaluation of Imnovid (pomalidomide; Celgene, US) on 4 January. Imnovid is indicated in the treatment of patients with multiple myeloma in combination with dexamethasone, who have received at least two prior therapies, including both lenalidomide and bortezimob, and whose diseases has progressed after the last treatment.
Imnovid is an orphan medicine, and under German law, orphan medicines are considered to have an additional benefit by virtue of their marketing authorisation. However, this only applies when the medicine concerned incurs a financial cost to Germany's statutory health insurance (GKV) funds of less than EUR50 million (USD53.9 million) over the course of 12 months. Imnovid exceeded this threshold, following its initial assessment by the G-BA completed in February 2014, and thus it has been evaluated by IQWiG.
The G-BA identified two treatment groups, and two appropriate comparator therapies. In the case of patients for whom targeted therapy is appropriate, the comparator was set as a patient-specific therapy selected by the doctor in accordance with the indication (largely dependent on prior therapies). In the case of patients for whom targeted therapy is not appropriate, the appropriate comparator was set as BSC.
In the case of patients for whom targeted therapy is appropriate, IQWiG stated that the data submitted – based on one single clinical study – was not suitable to derive an additional benefit. The reasons given were the lack of consideration of individual factors behind the responses of patients in the comparison arm, such as prior therapies, as well as the fact that the high doses of dexamethasone given to patients in the comparison arm do not comply with its authorisation, according to IQWiG.
In the case of patients for whom a targeted therapy is not appropriate, IQWiG stated that the producer submitted no study data. Thus, IQWiG decided that Imnovid showed no indications of an additional benefit in this indication.
IQWiG's dossier evaluation summary for Imnovid can be accessed here, in German.
Tafinlar and Mekinist show additional benefits in combination, Mekinist shows none in monotherapy
IQWiG also published dossier evaluations for the Novartis drug Mekinist (trametinib) in monotherapy in the treatment of inoperable or metastatic BRAF V600 mutation-positive advanced melanoma, as well as another dossier evaluation for Mekinist in combination with another Novartis drug approved in this indication, Tafinlar (dabrafenib). Since September 2015, these drugs have been approved in combination for the treatment of the aforementioned indication.
In the case of Mekinist in monotherapy, the appropriate comparator set by the G-BA was Zelboraf (vemurafenib; Roche, Switzerland). However, IQWiG reported that it was not possible to deduce an additional benefit from the data submitted, which were based on an indirect comparison study. Therefore, IQWiG decided that Mekinist in monotherapy did not demonstrate an additional benefit.
In the case of the two drugs in combination, Zelboraf was also set as the comparison therapy. In this instance, IQWiG was satisfied that the randomised, active-controlled study on the basis of which data were submitted was appropriate for assessing the additional benefit of the drug. IQWiG decided that in the case of women, there was a hint of an additional benefit with regard to overall survival, although not in the case of men. It also saw advantages for the combination therapy in a range of other endpoints, including health-related quality of life, but stated that there was a lack of subgroup analyses in the dossier.
In summary, IQWiG decided that in the case of women, Tafinlar and Mekinist in combination showed a hint of a major additional benefit, while in the case of men, the combination showed hint of an unquantifiable additional benefit. The full IQWiG summary of these two dossier evaluations can be accessed here, in German.
Outlook and implications
In the case of each of the four drugs (or combinations) considered above, there will be a consultation period of around three months, following which the G-BA will issue its final resolution. The producers have an opportunity to submit additional data or evaluations which could influence the eventual decision of the G-BA.
It is noteworthy that when the G-BA carried out its assessment of the additional benefit of Imnovid in the first instance, it decided that the drug showed a considerable additional benefit. However, IQWiG decided that it showed none. It will be interesting to see whether the G-BA would downgrade its original assessment prior to the submission of a value dossier.
Also worthy of note is that in the female population group, the combination of Tafinlar and Mekinist achieved the highest possible innovative score in the German benefit assessment system – major additional benefit.