Polatuzumab vedotin is a drug for the treatment of diffuse large B-cell lymphoma (DLBCL), a rare disease. After the revenue of the drug with the statutory health insurance exceeded an amount of 30 million euros in the previous 12 months, the manufacturer submitted a dossier for benefit assessment of polatuzumab vedotin versus the appropriate comparator therapy. In an early benefit assessment, the Institute for Quality and Efficiency in Health Care (IQWiG) has now investigated whether polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin and prednisone offers an added benefit over rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone in adult, previously untreated patients.
The submitted study data show both positive and negative effects of polatuzumab vedotin; overall, an added benefit has not been proven. Nothing special so far - but what is remarkable is that analyses specified in the statistical analysis plan that were explicitly intended for health technology assessments such as the benefit assessment in Germany were not provided.
Significant redactions in the study protocol
In its dossiers, the manufacturer presented data from the POLARIX study. In this ongoing double-blind RCT, separate analyses for HTA were planned according to the statistical analysis plan, which were to be reported separately from the primary study report. These analyses should address further efficacy outcomes and patient-reported outcomes, such as complete response two years after randomization. However, analyses of these outcomes are neither included in the study documents nor in the further documents submitted with the dossier.
"So the joy about a study that should not only serve the approval but also benefit assessments is swiftly followed by disappointment," comments Philip Kranz, Division Head of IQWiG's Drug Assessment Department. "We have two versions of the study protocol: the complete version from the dossier, which foresees special analyses for HTA, and the published version, in which 'for HTA' was redacted. The manufacturer did not provide a reason for this approach. Selective reporting is obvious here."
G-BA decides on the extent of added benefit
At the same time, IQWiG assessed another therapeutic indication for polatuzumab vedotin; no suitable data were available for this indication.
The dossier assessments, for which the G-BA is responsible, are part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG). After publication of the dossier assessments, the G-BA conducts commenting procedures and makes final decisions on the extent of the added benefit.