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Developing an Early Stage Biopharmaceutical Asset in Europe: Navigating Treacherous Waters

October 29, 2019


Written by: Bami Oshinowo Mónica Martín de Bustamante Temitope Coker

When biopharmaceutical products launch in the European Union, even experienced manufacturers can struggle to overcome the demanding standards of European payers. The complex market authorisation requirements and subsequent access decisions across 28 countries can lead to challenging timelines and confusing rollouts. Unfortunately for manufacturers, the future of European commercial planning is likely to become more challenging, as nations look to raise evidence standards and increase the scrutiny of pricing. Looking ahead over the next ten years, CBPartners is tracking many policy and payer trends which will affect the playing field for future launches. Examining these key trends in detail can provide further understanding of how manufacturers can create an “Early Asset Success Plan” for new products.

The top three trends that impact product launch in Europe

In this post, we will focus on some of the trends that are likely to have a significant impact on how manufacturers prepare for products coming to Europe over the next five -ten years, namely:

Evolving Health Technology Assessment (HTA) criteria for Orphan products

Beginning with our first trend, this evolution is primarily caused by the increased budget impact of orphan drugs. The existing legislation at the European and national levels incentivises development of orphan products, leveraging accelerated processes and pricing flexibility to attract manufacturers to invest in small populations. While these policies have worked well to date, many payers believe that they may be working too effectively – resulting in numerous orphan products being priced at very high levels. As an example, consider multiple myeloma: this orphan cancer was historically devoid of treatment options, but today there are numerous therapies and combination regimens available. While this is great for patients, many of these products have monotherapy prices over EUR 50,000 per year, resulting in enormous cumulative budget impact. In order to cope with this cost, payers are looking to change how they treat orphan products to dial down the incentives package.

A prime example of this trend is happening in Germany (GER), where the Gemeinsamer Bundesausschuss (G-BA) is making a variety of changes to better track orphan product use and evidence. The new Law For Safety in Supply of Pharmaceuticals (GSAV) requires orphan products to participate in a registry scheme in order to generate greater real-world data. This limits manufacturers’ ability to shape the evidence and value proposition, as they will have less control over data generation and analysis. Furthermore, that data will then be used at re-assessments of the product’s added benefit rating, potentially putting a product at risk for downgrading to a lower added benefit. This could in turn constrain the context for pricing negotiations of a product, lowering outlook over time.

To meet this trend, manufacturers should re-assess the cost-benefit ratio of pursuing an orphan designation. While today this is usually a positive ratio, the future of increased costs of pursuit and decreased benefits could change that for some products. The decision to pursue the designation should be made with a clear-eyed view of the possible changes to this ratio, and how it may change over time. Real-world evidence created over time may not reflect what has been observed in clinical trials – internal expectations and access forecasts would need to be adjusted as this evidence emerges. Additionally, as countries like GER seek to impose infrastructure around orphan products for monitoring outcomes and use, manufacturers should proactively engage in these processes. By participating early in the design of such programs, manufacturers will be better positioned to use them for future products and optimally collaborate on real-world data generation.

Increased expectations for early HTA dialogue

Continuing to our second trend, national HTA bodies are providing expanded opportunities for early communication with manufacturers. This kind of pre-submission exchange, while not uncommon today, is likely to become a standard in some markets in the near future. This need for greater early alignment has many drivers, such as the constraint to single-arm trials for some highly innovative therapies and the fragmentation of some disease spaces (leading to a need for alignment on trial comparators, etc.,). Again, consider myeloma as an illustration of this point. Perspectives on the standard of care vary across markets, as many newer products are not launching with the head to head data versus other novel entrants that would drive standards development. The orphan size of the patient population has resulted in a highly treatment-experienced population, constraining the capability of new products to conduct efficient trials in some sub-populations. In view of these challenges, manufacturers must understand how to best engage with each payer in advance of their submission and optimise their ultimate evidence package.

Fortunately for manufacturers, the high-level strategic response to this trend is straightforward – simply engage in more early dialogues with HTAs. The cost of doing so is quite low, and these exchanges can provide significant clarity on clinical trial design choices or economic modelling assumptions; however, to optimise the outcomes of these sessions requires additional effort. While HTAs are sometimes in alignment across nations on key evidence questions, they do not always agree. If a manufacturer meets early with the G-BA, they may receive a recommended comparator or biomarker which The National Institute for Health and Care Excellence (NICE) or the Haute Autorité de Santé (HAS) thinks will add no value to the trial. Therefore, it is incumbent upon manufacturers in their early engagement efforts to act as a nexus, bringing together different key opinion leaders and HTA members in order to establish a consensus opinion. This will give their evidence package a more robust and accepted basis, increasing the opportunity for positive pricing and market access outcomes.

Increasing importance of patient perspective and advocacy

In our final trend, we observe an increasing role for patient advocate stakeholders and patients themselves in the years to come. While the significance of patient advocacy varies across therapeutic areas with factors like severity of disease and size of patient population, in some areas of high unmet need there are patient organisations with substantial leverage over the healthcare decision making process. As these groups find success in pursuing their patients’ goals, the development of a more direct and consistent channel for patient perspectives in product assessment will continue to increase their importance.

At its most intense point, this patient input can be seen in groups pressuring government bodies to provide access to critical medicines. One example can be seen in the Netherlands with the spinal muscular atrophy (SMA) product SPINRAZA from BIOGEN ($BIIB). At first assessment, the Netherlands would only cover the product for patients under 9.5 years of age, citing limitations in the patient population of the clinical trial. In response to this restriction, organisations such as Muscle Diseases Netherlands created a mass media campaign, including direct communications with policymakers as well as public articles and stories of patient journeys. After months of effort, the Zorginstituut in the Netherlands agreed to the groups’ requests and expanded coverage to all patients.

For manufacturers seeking to engage with patient advocacy, the benefits extend far beyond their ability to influence political actors. Patient organisations can provide perspectives on clinical trial designs in the areas of endpoint selection and measurement and can also help reveal aspects of disease or treatment which can be useful to contextualising a new product’s value. Collaboration can also be highly beneficial for patient groups, especially in small or under-developed disease areas. Manufacturers can play a pivotal role in bringing patients together, helping them share their stories, and providing the infrastructure on which patients can build a community together.

How to navigate future success for biopharmaceutical product launches in Europe

While there are many more rising trends that will impact the future of EU bipharma, across these trends it is clear that a key requirement for future success is advance planning. The products which face the greatest challenges at launch are usually those which prepared the least, both at the local team level and in collaboration with global manufacturer stakeholders. The earlier that the value, access, and pricing teams can collaborate on a coherent vision for a product’s launch, the better. While CBPartners is confident in the trends described herein, it is always difficult to know what new developments may shape the commercial outlook for new therapies. In these uncertain times, the manufacturers that succeed will be those that are best able to adapt through early preparation.

This theme of early action also extends to the other trends CBPartners is monitoring at our Early Value Access & Pricing and Commercial Planning Center of Excellence. This team of experienced consultants focuses specifically on these planning challenges and adapting successful strategies to an evolving landscape. CBPartners will continue to monitor the European policies and payers, as well as trends in our other regions of expertise in LatAm, AsiaPac, and the USA. If you will be attending the 2019 ISPOR EU Summit in Copenhagen, we hope you will join us for our workshop W21 on Wednesday, 6th November, from 14:00 – 15:00 during Breakout Session 11.