ATMPs in Germany - Provenge®

▶️ Provenge (active substance: sipuleucel-T) was approved for treatment of prostate cancer in September 2013. It is a somatic cell therapy product. The market authorization was withdrawn and expired in May 2015. Provenge is no longer available in Germany.

🏆German HTA rating:
Provenge was the first ATMP assessed in German HTA. The German HTA rating in March 2015 resulted in a hint for a non-quantifiable additional benefit. The HTA was based on three RCTs. In both study arms of these RCTs patient's own antigen-presenting cells were isolated. In the intervention arm the cells were activated to the active substance sipuleucel-T, in the control arm the cells were re-infused without activation (sham treatment). This comparator was the correct implementation of the appropriate comparator, being the watch-and-wait strategy. Despite positive effects in overall survival, the extent of the additional benefit cannot be quantified, because of uncertainties in the study design.

In addition, the resolution on HTA is limited until April 2018 to allow for generation of more reliable evidence for overall survival, morbidity, and quality of life. However, Provenge was not reassessed as the market authorization was withdrawn before.

💵 Launch price: € 25.000 per dose. The course of treatment is completed after three doses. Reimbursement price: not applicable (the reimbursement price was never listed, as the market authorization was withdrawn)

📘 Special features of reimbursement:
Provenge was reimbursed before market authorization was withdrawn; no particularities were apparent.

💡 Overall survival is the most important endpoint in oncology, because results on progression events are not considered patient relevant for German HTA. However, the inevitable complex study designs of RCTs for ATMPs, such as crossover, post-progression treatments and rescue therapies, can bias the results of overall survival. This might lead to a downgrade of the additional benefit and a limitation of the resolution. Therefore, the regular methodology of HTA was utilized to ATMP without exemption.