Germany's IQWiG has published its summaries of its dossier evaluations for two new oral type-2 diabetes drugs from the SGLT2 inhibitor group, deciding that both show no additional benefit.
IHS Life Sciences perspective | |
Significance | IQWiG has recently published its summaries of its dossier evaluations for two SGLT2-inhibitor drugs used in the treatment of type-2 diabetes – the Eli Lilly / Boehringer Ingelheim drug Jardiance (empagliflozin) and the Janssen-Cilag fixed-combination drug Vokanamet (canagliflozin and metformin) – concluding that neither demonstrates any additional benefit. |
Implications | This follows on from a series of negative regulatory decisions in Germany for new oral type-2 diabetes drugs in recent years. |
Outlook | It is not completely clear whether one or both – or neither – of the drugs assessed will be eligible to enter price negotiations, as there is currently only one SGLT2 inhibitor marketed in Germany. There is a strong possibility that one or both of the companies will opt to withdraw their product from the German market, adding to a long series of type-2 diabetes drugs withdrawn in recent times, because of unfavourable regulatory decisions. |
Germany's Institute for Quality and Efficiency in Healthcare (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen: IQWiG) published the summaries of its dossier evaluations for two new type-2 diabetes drugs on 17 November; these are Jardiance (empagliflozin), marketed by Boehringer Ingelheim (Germany) and Eli Lilly (US), and Vokanamet (canagliflozin and metformin), marketed by Janssen-Cilag, the European subsidiary of US pharma major Johnson & Johnson. Both products are from the group known as sodium-glucose co-transporter 2 (SGLT2) inhibitors (albeit Vokanamet is a combination product), which have only started coming on to the market since 2012.
Jardiance assessed to demonstrate no additional benefit
Jardiance is indicated for the treatment of adults with type-2 diabetes who are unable to attain sufficient control of blood-sugar levels with exercise and diet alone. IQWiG decided that based on the evidence in its dossier, Jardiance demonstrated no additional benefit. Five different treatment settings were identified for the drug, and the Federal Joint Committee (Gemeinsame Bundesausschuss: G-BA) established the appropriate comparator therapies for each of these.
Used in monotherapy – by patients who cannot take metformin – the G-BA set the comparison therapy as a sulphonylurea; used in combination with metformin, it set metformin and a sulphonylurea as the comparison therapy; used in combination with one other blood-sugar lowering medicine, it set metformin and a sulphonylurea again as the comparator; used in combination with at least two other antidiabetic medicines, it set metformin and human insulin as the comparators; and in combination with insulin, metformin and human insulin were again set as the comparators.
In all treatment settings apart from in combination with one other blood-sugar lowering drug, IQWiG stated that no relevant data was submitted that could be considered for the evaluation – without going into more specifics – and therefore it concluded that in these settings, no additional benefit was demonstrated.
In the one treatment setting for which IQWiG decided that the data submitted was relevant for consideration, the producer submitted data from one direct and two indirect comparison studies. Commenting on a study in which Jardiance was compared with a sulphonylurea (glimepiride), IQWiG states that in the comparison arm of the study, there was insufficient flexibility in efforts to achieve HbA1c targets, with patients being treated with glimepiride in doses between 1mg and 4mg, while in the case of patients in the Jardiance-arm, the dose remained constant at 25mg. IQWiG concludes that as a result, not only two medicines but two therapy strategies need to be compared in this study data. IQWiG also points out that the dosage of Jardiance – 25mg – is 2.5 times higher than that of the 10mg dose associated with its marketing authorisation. Although noting that with Jardiance, there appeared to be lower incidence of hypoglycaemia, it was also associated with more incidence of genital infections and diseases of the kidney and urinary tract than glimepiride. IQWiG considered the data from the indirect comparison studies not to be admissible for evaluation. The summary of IQWiG's dossier evaluation of Jardiance can be accessed, here, at the Institute's website, in German.
Vokanamet judged to demonstrate no additional benefit
Vokanamet has the same indication as Jardiance; the single-ingredient version, Invokana (canagliflozin), has already completed its benefit assessment, with the G-BA concluding that it demonstrated no additional benefits (see Germany: 5 September 2014: Germany's G-BA sees no additional benefits from J&J's oral type 2 diabetes treatment Invokana). IQWiG has reached the same conclusion about the fixed-combination version.
Three different treatment settings were identified for Vokanamet: used alone, the appropriate comparator therapy set by the G-BA was a sulphonylurea (glimepiride or glibenclamide) and metformin; used together with a sulphonylurea or with insulin, then the appropriate comparator therapy was set as human insulin plus metformin.
IQWiG stated that in the case of Vokanamet used together with a sulphonylurea, or used together with human insulin, no data from direct or indirect comparison studies was provided, making it impossible to evaluate the extent of the additional benefit. In the case of Vokanamet used on its own, compared with a sulphonylurea and metformin, data from a pivotal study was submitted, but IQWiG concluded that it was not possible to evaluate the extent of the additional benefit in this case. This is because, due to the study design, it was comparing not only two different medicines, but also two different therapy strategies, making it very hard to identify which benefits were the result of the medicines and which were the result of the different therapy strategy. The full summary of Vokanamet's dossier evaluation can be accessed at the Institute's website, here, in German.
The G-BA is due to give its final resolution on the early benefit assessment of both drugs on 8 December.
Outlook and implications
Germany's G-BA and IQWiG have taken a tough stance on newer type-2 diabetes medicines coming on to the market, with particular reference to the wave of new oral type-2 diabetes drugs that have been appearing in the past decade: SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. In late September, Janssen announced its intention to withdraw Invokana from the German market (see Germany: 24 September 2014: Janssen to withdraw Invokana from German market following unfavourable G-BA opinion), and it would not be surprising if it were to make the same decision about Vokanamet, or if Boehringer and Eli Lilly opt to withdraw Jardiance. These partners already have experience with the German authorities' tough stance on new oral type-2 diabetes drugs, having withdrawn their DPP-4 inhibitor Trajenta/Tradjenta (linagliptin) from the German market several years ago after an unfavourable early benefit assessment. Indeed, there has been a string of negative decisions and recommendation in recent months for medicines indicated to treat type-2 and type-1 diabetes by the G-BA and IQWiG.
The G-BA decided that the first SGLT2 inhibitor to come on to the German market, AstraZeneca's Forxiga (dapagliflozin) showed no additional benefit back in mid-2013, and the company withdrew the drug when talks with the National Association of Statutory Health Insurance Funds broke down (as the first drug of this class it could not be entered into the reference-pricing system, and therefore qualified for price negotiations). However, eventually, the company opted to continue marketing its product in Germany, after concluding an agreement on the reimbursement price. Given that Janssen has withdrawn Invokana from the market, it may be that Jardiance (or potentially Vokanamet) will qualify for price negotiations, as there need to be more than two products to create a reference group.