The approval for early innovation products is gaining momentum throughout the EU. However, lack of confidence on the results presented and suboptimal quality access to drugs are causing this momentum to slow in Spain. Experts Ana Mozetic, Carlos Ardévol, and Paloma Gutiérrez outline how manufacturers can overcome these hurdles.
Early innovation authorizations are gaining momentum in the EU
Over the past few years, a growing number of early innovation products – drugs approved with only phase I/II trials and shorter clinical development processes – have achieved approval from the European Medicines Agency (EMA) with limited evidence. This trend is expected to continue in the coming years as drugs become more “specific” (i.e., targeting a specific mutation).
Data from the European public assessment reports published since 2016 shows that approximately 300 new active substances have been authorized by the EMA, and the number of approvals based on phase I/II trial evidence has steadily risen. There was an average of five approved per year in the period 2016-2019, while 10 and 11 in 2020 and 2021 respectively. This increase in numbers suggests the EMA has adopted the role of “innovation advocate,” approving products that are not necessarily supported by robust phase III studies.
What are the reasons behind this trend? European authorities tend to approve early innovation products based on promising, yet immature, data and accelerate the clinical development process, since unmet need is high in the target populations for these drugs. The level of unmet need is determined by the severity and low prevalence of the pathologies these products address. These considerations often lead to a conditional approval, where authorities seek future confirmatory data.
Unrequited confidence from Spanish authorities
When entering the Spanish market, drugs with immature evidence at launch still struggle to achieve public funding. During the assessed period (2016-2021), 34 drugs with Phase I/II evidence at launch were authorized in Spain, but only 11 of them achieved funding.
When entering the Spanish market, drugs with immature evidence at launch still struggle to achieve public funding. During the assessed period (2016-2021), 34 drugs with Phase I/II evidence at launch were authorized in Spain, but only 11 of them achieved funding. |
However, this does not mean that the rest of the products received a negative funding decision. In fact, only eight of them were rejected, while some are still under study or requesting funding, and for others it is unclear whether they have requested public funding. In addition, not all of them managed to secure funding with the study they initially used to apply for authorization, and many had to wait for confirmatory data from a Phase III study to achieve funding.
Another cause for concern is the time that it takes for these products to be included in the national portfolio. On average, it took around 440 days for drugs with Phase I/II evidence at launch to achieve a positive decision compared to the usual 300-day average for regular drugs. This significant difference in approval times leads to deferred market access.
Suboptimal quality of access: Long processes and major constraints
Furthermore, early innovation products face more hurdles even if they are funded. They are often subject to additional conditions, which can lead to suboptimal quality of access. The greatest challenge these drugs face is addressing the uncertainty posed by their immature evidence. These products are usually cutting-edge technologies that promptly arrive to the pricing and reimbursement process, generating high uncertainty for Spanish decision-makers. In addition, it takes a long time to see whether these treatments are indeed cost-effective and affordable for the system.
Products of this nature tend to establish financial or outcome-based agreements with authorities setting criteria, objectives, and variables to monitor patients under these treatments. In the short to medium term, these agreements, which are now seen on an ad-hoc basis, are expected to become more widespread, as they provide a level of financial or clinical certainty, and diversify risks between manufacturer and payers.
In conclusion, access for early innovation products is poor, as only 40 percent of them eventually reach the Spanish market. They also face substantial barriers, as well as longer processes and negotiations.
No improvement prospect in Spain for these drugs
In early 2020, the Spanish government introduced the Plan for the Consolidation of Pharmaceutical Therapeutic Positioning Reports in the National Health System (Plan para la consolidación de los informes de posicionamiento terapéutico de los medicamentos en el Sistema Nacional de Salud), which may even further hinder access for these products.
The plan included a new prioritization matrix for scoring and ranking drugs according to specific criteria to accelerate the development of therapeutic positioning reports (IPT). Most early innovation products fail to meet the criteria (e.g. improved safety profile or potential incremental clinical benefit compared to already funded alternatives) due to the lack of data and end up being deprioritized.
A negative result from this prioritization can lead to a longer time to market, since negotiations cannot start until the IPT has been developed. This type of delay can lead to authorities waiting for Phase III data (if expected) before eventually funding this type of innovation. These hurdles, and the current budget constraints, create uncertainty and an unfavorable market environment for manufacturers of early innovation drugs.
Moreover, although the time since the funding request until the imitation of the negotiation process can be extended, the Ministry of Health has followed a take-it-or-leave-it approach for recent negotiations. This has resulted in several negative funding decisions and has led to no possible access in the public setting.
Advice for manufacturers
Either way, there is still some proactive steps that can lead to a positive outcome. Manufacturers should identify the real unmet need in the indication and involve several stakeholders (e.g., KOLs, patient associations) to ensure national payers are aware of the product’s value beforehand. Additionally, uncertainties around the product and pain points from payers should be identified prior to interactions with payers.
Considering this, a clear negotiation strategy should be defined with studied steps and concessions. This can lead to a more favorable positive funding decision for both public and private parties, especially considering the “one shot” nature of the process.
