Almost 2 years after the launch of EMA’s PRIority MEdicines scheme (PRIME), 31 compounds have been accepted so far.  PRIME status means more than fast, conditional or adaptive approval.  With the recent introduction of the Medicines Adaptive Pathways (MAPs) PRIME-drugs will continue their clinical development beyond approval.  A strong move towards Real World Evidence (RWE)! The Innovative Medicines Initiative (IMI) introduced GetReal which outlines how to collect RWE data after PRIME approval. It rapidly obtained endorsement by EMA, patient organizations, academia and pharma alike.

But what about the payers? Will they be willing to pay for drugs with premature data only? 

And if so, under which conditions? In times of skyrocketing new drug prices for breakthrough cancer drugs and Advanced Therapy Medicinal Products (ATMPs), payers may believe all hell is breaking loose! 

Let’s have a look at IQWIG’s point of view on this very topic.

The PRIME program is the new European counterpart of the FDA’s fast-track approval of drugs with Breakthrough Therapy Designation. Since its launch in March 7th 2016, there has been a tremendous interest in the PRIME pathway with 31 compounds accepted so far, but growing steadily.

PRIME status is granted based on strict criteria for innovative medicines with high unmet need. It is founded on a tight manufacturer-regulator dialogue and a commitment to integrate RWE early on into the development.

The Adaptive Pathway reduces or even eliminates the cost of phase 3 but requires major investments in rigorous RWE. There is no complete agreement yet on what this really means in practice. But all stakeholders do agree that RWE is badly needed to compensate for the shortcomings of registration trials.

However, as long as payers are not completely on board, Adaptive Pathways aren’t without risks to the pharma industry. As products will enter the market with premature evidence, payers may force manufacturers into suboptimal prices, financial deals and registry-based pay-for-performance agreements which are currently not in place in many European countries due to cost and organizational issues.

Only a few months after PRIME’s kick off, IQWiG expressed serious doubts: “Evidently neither industry nor EMA has a clear idea about how to reliably use real-world data and how to draw conclusions about benefit and harm.”

After the first PRIME applications IQWiG also criticised EMA for the “unacceptable” lack of transparency, the vagueness of the submitted RWE plans and the collection of safety data. They concluded that it is “high time to pause for a moment and rethink the whole concept, instead of considering more drugs in the consultations on adaptive pathways, as planned by EMA".

The German market access process is very complicated and probably highly resistant to change. IQWiG is known to be rigorous and strongly focused on RCT, often questioning whether the study population reliably represents the real population. Interestingly the GBA always asks for observational data while IQWiG remains sceptical about the move towards RWE. Does this represent a gap between the GBA and IQWiG? Or, are these only transient growing pains of the German stakeholders that will ultimately be obliged to accept the changing rules of the game? 

Today most European payers are doubtful and unable to imagine how Adaptive Licensing will pan out in terms of pricing and reimbursement.  However, it may ultimately turn out to be less problematic than it seems today.   In a few years’ time, we may be looking back and realize it has just been a storm in a teacup.  The acceptability of early access may largely be based on building trust and understanding between the industry and payers, and this will take time and experience.

During our daily conversations with European payers we see how they gradually adapt to adaptive licensing. They get used to think out of the box and consider new financial deals and advanced registries. Payer decisions also increasingly also tend involve patients in the’ decisions are also increasingly taken with active involvement of patients, that will ultimately benefit most from potentially life changing PRIME drugs.

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