In the context of the European joint action iPAAC, innovative Partnership for Action Against Cancer, the WP9 dedicated to innovative therapies in cancer, conducted a study assessing the access to innovative immunotherapies in Europe, in terms of reimbursement as well as early access programs.

After a preliminary review of HTA opinions, questionnaires regarding conditions of reimbursements and early access to checkpoint inhibitors and CAR-T cells were sent to iPAAC partners in December 2018. External stakeholder opinions on access to innovative immunotherapies were then collected.

In total, replies were collected from 23 countries. Four countries had limited access whereas on the opposite, 7 countries had high access with over 15 indications out of 22 reimbursed with no restrictions compared to European marketing authorization. 
The best access in terms of reimbursement was observed for pembrolizumab as monotherapy for the treatment of advanced melanoma: it was reimbursed in 90.5% of countries. However, lots of restrictions of reimbursement were identified for the other indications in melanoma such as reimbursement only for BRAF-wild patients, restrictions on patients strictly presenting clinical trials inclusion criteria like ECOG 0/1 or no brain metastasis. Despite its extension of indication, the access to ipilimumab for pediatric patients was still very limited. 
Controversial results were also observed for indications like urothelial carcinoma for which pembrolizumab and nivolumab were not reimbursed in about 20% and not yet assessed in 30% of the countries replying. This is correlated with several negative opinions for this indication from HTA agencies such as NICE, SMC Scotland and IQWIG. For Hodgkin lymphoma, it was noted that there was still a third of countries for which the reimbursement of pembrolizumab and of nivolumab had still not be assessed almost 2 years post EMA approval.
About half of the countries (10/22, 45%) mentioned that they had an existing program enabling early access to innovation therapies against cancer (before marketing authorization or before extension of indication). This includes compassionate use programs with financial support provided by pharmaceutical industries, but some countries have other kind of programs in place with public financing, such as France, Portugal and Germany.

Opinions regarding the access to innovative immunotherapies in Europe were collected from 54 stakeholders from 20 different countries including healthcare professionals, HTA agencies, health & medicines agencies, cancer institutes and patients. About 55% of the respondents thought that the system in place in their country/region enabled a proper access to innovative immunotherapies in terms of reimbursement. Three main factors leading to restrictions of reimbursement and thus limiting the access to innovative therapies were identified: the low level of scientific and medical evidence supporting marketing authorization, missing direct comparison data with alternative therapies, and high costs. 
Less than half of the repliers (47%) were able to say that there was an existing program enabling the early access to innovative immunotherapies prior marketing authorization in place in their country. However, the satisfaction regarding implemented programs was high: 80% of the persons who replied that there was such a system in place in their country were satisfied with their implemented system. Two main aspects stood out for the implementation of frameworks and programs to enable early access to an innovative therapy: the need to have clear defined pathways and frameworks, and the need to have strong discussion among the different stakeholders. 
Early access programs as seen as a good help to bridge the gap between the granting of marketing approval and definition of the price and the decision for reimbursement. It is also important to have these kinds of programs for patients who would have no other alternatives. On the other hand, it was also mentioned that early use should be very restrictive to clearly outstanding drugs. In the case of early access, patients should be clearly informed that they are receiving a drug with no approved marketing authorization.

Access to innovative cancer immunotherapies: an iPAAC Work Package 9 study focusing on checkpoint inhibitors and CAR-T-cells