Already in 2013, the German Institute for Quality and Efficiency in Health Care (IQWiG) examined in an early benefit assessment whether ingenol mebutate offers greater benefit than the appropriate comparator therapy (ACT) for patients with actinic keratosis. With the drug manufacturer presenting no suitable study data at that time, the conclusion was "added benefit not proven". Due to new scientific findings, the manufacturer now applied for a new assessment.
In a randomized controlled trial, ingenol mebutate was now compared directly with the ACT diclofenac/hyaluronic acid. The study showed advantages in one outcome, i.e. complete clearance of visible skin lesions. It remains unclear whether this effect is permanent, however, as the study was ended after 120 days. Regarding other outcomes, there were no statistically significant effects, or no data were available. In particular, it remained unclear whether the treatment prevents squamous cell carcinoma, which can develop from actinic keratosis. Overall, this resulted in a hint of a non-quantifiable, at most considerable, added benefit of ingenol mebutate versus diclofenac/hyaluronic acid.
Good studies are useful even after approval
"Five years ago, the manufacturer presented nothing to show an added benefit of its drug," says Stefan Lange, Deputy Director of IQWiG. "There simply was no study comparing the substance, which was new at the time, with the ACT." According to Stefan Lange, the newly submitted data from a study conducted in the meantime have changed this situation. "Good data are required not only for the approval. Also afterwards, randomized controlled trials can generate the knowledge we need for an early benefit assessment. And this pays off - for patients as well as for the manufacturers," he adds.
G-BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.