By Leela Barnham, indepdendent health economist, leels@btinternet.com

The idea is simple: buying together can help countries secure the best deal.

Apply that to the fragmented and diverse landscape of drug pricing and reimbursement in Europe and the reality becomes a lot more complicated. But there are some European countries that are doing just that. The BeNeLuxA initiative Set up in 2015, the BeNeLuxA initiative aims to deliver sustainable access to innovative therapies. Starting first with the Ministers of Health of Belgium and the Netherlands, the initiative now includes Luxembourg, Austria and last, but by no means least, Ireland, which joined in June 2018. The publicly available Terms of Reference show how the initiative approaches the work. The group works together in a variety of ways, from horizon scanning and information sharing to cooperating on Health Technology Assessment (HTA) and joint negotiations on price. Initial reactions from industry were said to have been dismissive, as getting more than one country to agree to a deal at the same time as another was seen as a difficult goal.

Progress across the programme

Progress is being made by BeNeLuxA across its work programme. On horizon scanning, while work has been underway, there’s little to note in terms of published outcomes, but interest is supposed to be high with as many as 20 countries wanting to take part. With plans to commission an International Horizon Scanning Initiative (IHSI) in 2019, more will emerge soon. Progress seems to be more visible when it comes to information sharing. So far it seems to have focused on patient registries and biosimilars, supported by meetings and webinars. Many more documents have been produced on HTA. While there have not been joint HTAs for all six of the drugs looked at, there has been a joint HTA (and it was subsequently updated) for Vertex’s cystic fibrosis treatment Orkambi (lumacaftor/ivacaftor), Intercept’s Ocaliva (obeticholic acid) for primary biliary cholangitis and for Biogen’s Spinraza (nusinersen) for spinal muscular atrophy (SMA).

The first joint negotiation to deliver a deal: Spinraza

Simple economics would predict that the bigger the buyer, the better the deal. But that relies on successfully concluding the deal. So far, BeNeLuxA has only been successful in completing formal joint negotiations when buying Biogen’s Spinraza (nusinersen). An earlier BeNeLuxA pilot for Vertex’s Orkambi (lumacaftor/ ivacaftor) failed to lead to a deal in both 2016 and 2017. So what’s the deal for Spinraza? Spinraza is classified as an orphan drug for the treatment of spinal muscular atrophy (SMA), a rare neuromuscular disorder that occurs in one birth in every 6,000 to 10,000. Spinraza is the first drug for the condition authorised in Europe.

Under the Spinraza deal – announced in July 2018 – only Belgium and the Netherlands worked together, and the deal is not the same for each country. In Belgium reimbursement covers all age groups. In the Netherlands, reimbursement only covers patients up to the age of nine and a half, which means that 80 children with SMA in the Netherlands will be able to access Spinraza under the deal. The deal includes a refund to the payers, but just how much hasn’t been revealed. The Dutch say that the price has been reduced to an acceptable level from the list price of €83,300 per injection, leading to a cost for the first year of treatment of €499,800 and €219,900 thereafter. The Zorginstituut Nederland (ZIN) – the Dutch HTA agency – reportedly told the Minister that a price cut of 85% would be needed to make it affordable for the healthcare system in the Netherlands.

It is not known if the deal generated that kind of cut, but whatever cut was agreed, it seems to have been the same for both the Belgians and the Dutch. The Ministry in the Netherlands described how Spinraza is reimbursed in both countries under ‘comparable financial conditions’. It’s not just price that was subject to negotiation. In a way that has become almost business as usual for a number of orphan drugs, collection of real-world data is also part of the deal. Data will be collected on the safety, efficacy and use of Spinraza in day-to-day clinical practice in Belgium. There will also be additional research on the effect of Spinraza in subtypes of SMA. In the Netherlands there may also be an agreement for further research.

The deal is therefore best seen as an interim managed entry agreement, with a review of both price and reimbursement in the future. That will look at which patient groups should be reimbursed and build on the data that is being collected. Time will tell then, if reimbursement will continue and at what price. It must surely be likely though, that it will remain a joint negotiation, when the current deal runs out. The process did not just involve price negotiations, however, it also concerned a joint HTA. This cements HTA as a key enabler for working on negotiating a price, since it helps develop a shared – at least between the buyers – view on value. That focus on value flows more generally too: despite the scope to use purely buyer power in the negotiations, the negotiation framework has instead focused on negotiating the value of the product and not necessarily on getting the lowest price. That said, no-one except the company will know just how low it would be willing to go and whether or not the negotiations reached that point. Presumably the joint HTA also played a role in highlighting where the uncertainties lie and helped confirm the data needed to address them. The price negotiations started in February 2018, eight months after marketing authorisation came from the EMA for Spinraza, following EMA’s accelerated approval process. Getting a price agreed added more time, but deals were put in place ready to go live from August in the Netherlands, and September in Belgium.

Biogen said it worked with BeNeLuxA for 18 months to secure the deal, engaging even before the regulator gave its stamp of approval. The deal runs until the end of 2020.

Concluding a joint price negotiation successfully is a bit of a coup for the ministers in Belgium and the Netherlands. It illustrates to the industry that it is possible, albeit not without challenges. It’s also a bit of a coup for Biogen, enabling it to stand out as a company that is willing to sit down with two payers at once. That might well have saved the company some internal time and effort, but it’s still not going to make much difference to the resourcing needed to support pricing and reimbursement for Spinraza in other European countries.

The effort needed to secure reimbursement in some countries is likely to be considerable: for example, the UK’s National Institute for Health and Care Excellence (NICE) has signalled the need for further talks with Biogen, with draft guidance not recommending Spinraza’s use. The UK has between 1,200 and 2,500 children and adults with SMA; that makes the 80 patients in the Netherlands who will be reimbursed look like an even smaller group. Biogen says that it has been working with NICE and NHS England (NHSE) – who pay for specialist treatments – on a managed access agreement (MAA). Discussions are still under way.

The future for joint buying

With Ireland being the latest to join in June 2018, there is clearly interest in the initiative that goes beyond the founding countries. It was only this year that a deal was struck that made use of the joint price negotiation – and who could blame other countries for being cautious. The clincher that encourages other countries to join may be the prospect of a better deal with BeNeLuxA; however that remains confidential. For everything else, countries in Europe can be involved in a host of initiatives on horizon scanning, sharing policies and prices, HTA and buying together, as shown in the map above. On horizon scanning there are already efforts from the EMA – since it too likes to know what’s going to come its way – and also from the European network on Health Technology Assessment (EUnetHTA). On information sharing there is the Pharmaceutical Pricing and Reimbursement Information (PPRI) network, although it is wider than just Europe. There is MEDEV too, an informal cooperation on the assessment, pricing and reimbursement of medicines in Europe. There’s also Euripid, which sets out list prices.

On HTA there’s no shortage of work either. There is an HTA network in Europe, and the European Commission has set out proposals to formalise collaborative work on HTA, although that is still some time off and still needs to secure agreement on what are controversial ideas on just how much can be done together while still allowing member states in Europe to exercise their independence on pricing and reimbursement.

Alongside BeNeLuxA, similar initiatives on procurement include: the Baltic Partnership Agreement; the Romanian and Bulgarian initiative; the Nordic Pharmaceuticals Forum; the Declaration of Sofia; the Southern European initiative; the Central Eastern European and South Eastern European Countries Initiative, as well as the Valletta Declaration.

For both countries and industry, it’s a decision about where best to get involved to get the best out of working together. It may be worth waiting and seeing as a general strategy, as some efforts may fall by the wayside. BeNeLuxA has broken new ground, and it is the one to watch.