No data were presented for treatment-naÃ¯ve and pretreated adolescents with hepatitis B virus.
Scientists concluded that the antiviral drug tenofovir alafenamide (TAF) has no added benefit for patients with chronic hepatitis B virus (HBV), and that the drug manufacturer provided incomplete data.
In an early benefit assessment, scientists from the German Institute for Quality and Efficiency in Health Care (IQWiG) sought to examine whether TAF provided any added benefit in patients with HBV.
They found that the manufacturer presented no data in its dossier for treatment-naïve or pretreated adolescents 12 years and older. Additionally, data from 2 studies for treatment-naïve or pretreated adults were incomplete to a major extent, rendering it unsuitable for a benefits assessment.
The investigators also found that the delineation between treatment-naïve and treatment-experienced patients was contradictory, and the appropriate comparator therapy was partially not implemented. This means an added benefit was not proven for any of the 4 patient groups, according to the IQWiG.
All patients who had never received any oral medication were considered treatment-naïve. But patients previously treated with interferon using other forms of administration were allocated to the treatment-naïve group, contradicting the Federal Joint Committee’s specification.
Meanwhile, some patients who did not receive oral pretreatment were allocated to the treatment-experienced group without any explanation by the manufacturer. Therefore, the patient groups were inadequate.
The manufacturer also presented only incomplete data for the outcome category called specific adverse events (AEs) for the subpopulations. Most notably, data were missing for AEs that the overall studies showed significant differences to the disadvantage of TAF.
“This is an exceptional case because whole tables were evidently shortened,” said Thomas Kaiser, head of IQWiG’s Drug Assessment Department. “As an example in the assessment, we have shown this for one of the study data tables, of which we only received 3 of 38 pages. The situation was similar for the other tables on specific adverse events.”
Kaiser added that complete data are crucial for an accurate assessment.
“It is not up to the manufacturer to decide which adverse events are of interest,” Kaiser said. “To evaluate this is an important part of our statutory duty.”
The added benefit of TAF compared with other antiretroviral therapy was mainly derived from an improved tolerability profile. But certain AEs of the drug, such as nervous system disorders, cannot be ignored, according to the IQWiG.
In fact, these AEs occurred more frequently under a previously assessed drug combination with TAF in HIV treatment. Kaiser noted that complete data submission and due diligence in the analysis would have been required here.
The data were also inadequate in the treatment-experienced adults arm because the appropriate comparator therapy was not implemented. Each patient received a uniform treatment regimen rather than ART that was personalized for the individual patient.
Additionally, there were no data presented for treatment-experienced or treatment-naïve adolescents.
Overall, the added benefit of TAF in comparison with the appropriate comparator therapy is not proven for any of the 4 patient arms.
“This is particularly unfortunate because this is the first drug in several years to be approved for the treatment of hepatitis B,” Kaiser concluded.