A review of the challenges and proposals for improving patient access to advanced therapeutic medicinal products in the Netherlands

Executive Summary

RARE IMPACT is a multi-stakeholder initiative working to improve patient access to advanced therapy medicinal products (ATMPs). This patient-focused initiative aims to assess challenges and propose actionable solutions to concerns regarding access to these transformative rare disease treatments in Europe. Through engagement with health technology assessment (HTA) agencies, regulatory bodies, payers, patient groups, clinicians, manufacturers and other experts across Europe, RARE IMPACT partners identified challenges and have proposed solutions for better access to ATMPs in Europe.

This report aims to stimulate multi-level stakeholder discussions on patient access to ATMPs and is not intended to capture all challenges to patient access to ATMPs. The RARE IMPACT initiative was launched at the European Conference on Rare Diseases and Orphan Products in 2018.

To date, access to ATMPs has not been straightforward in the Netherlands

Of the first CAR-Ts to launch, one was included in the lock (sluice list) for expensive medicines and not granted automatic reimbursement, and the other was not granted reimbursement for one of its two indications. The next three ATMPs anticipated to launch in 2020 are also likely to be included in the lock. This reflects the scrutiny placed on high-cost orphan medicines in the Netherlands, a theme that was central to the Netherlands’ Presidency of The European Council in 2016.

Patient access to ATMPs in the Netherlands is primarily challenged by issues related to the assessment pathway and willingness-to-pay. The Netherlands employs a series of assessment protocols to control expenditure. In theory, hospital (in-patient) medicines, which all ATMPs are likely to be, are immediately eligible for reimbursement at the time of marketing authorisation. However, if the expected cost is high when the medicine is included in the basic package the Minister of Health, Welfare and Sport can first place the product in the lock. These products are subject to a cost effectiveness assessment with an €80K/ICER threshold. Being placed in the lock restricts the reimbursement of medicines until certain criteria are fulfilled and price negotiations are carried out with the Minister of Health, Welfare & Sport, which can take up to 9 months.

The Netherlands Care Institute has acknowledged that the innovation and price of ATMPs “may have an impact on the way in which these medicines are assessed for admission to the insured package and how they are applied”

Both the lock system and automatic reimbursement pathway pose challenges for ATMPs, but there are amendments that can be made to improve patient access without compromising the existing protocols.

Greater flexibility of evidence acceptability is necessary. ATMPs in rare diseases often have smaller populations, single arm or unblinded studies, and surrogate endpoints that may not be well established. Accepting this data as part of an adaptive assessment process may allow for early patient access while generating additional data. A new process has recently been introduced in the Netherlands that will expand the conditional marketing authorisation of new drugs developed for rare diseases to enable access while compensating for the lack of data provided at launch. This does however require the manufacturer to agree on a reduced price during this period. It is not yet clear how successful this reform will be in facilitating access to ATMPs.

The budget impact threshold that triggers the full lock assessment should be raised for ATMPs. For one-off treatments the budget impact is disproportionately skewed to the early years of introduction, versus treatments that are taken continuously. Managed entry agreements and innovative payment contracts can play a role in managing the budget impact and distributing cost over the duration of benefit. If ATMPs for rare diseases are to be assessed through the lock process, then the cost effectiveness methodology needs to be adjusted to reflect the specificities of one-off treatments in small populations.

The Netherlands is an active participant in the Beneluxa joint assessment initiative, which was initiated in response to a concern about high-priced medicines. The process seeks to align the methodologies and willingness-to-pay of participating countries. However, no ATMP or orphan-specific assessment processes exist and the same methodological challenges that are observed with the cost-effectiveness assessment in the Netherlands (during lock negotiations) are likely to manifest during joint negotiations. It is not clear that this pathway will facilitate early access to ATMPs.

Guidance is required on the implications for ATMPs within the Beneluxa process. Adjustments to the Beneluxa process for ATMPs should be explored though multi-stakeholder discussions focusing on assessment and cost effectiveness methods, outcomes based contractual agreements with multiple countries that allow for pooling of real-world data, and willingness-to-pay thresholds for ATMPs in rare diseases.

The Netherlands should seek to be a leader in driving cross-border healthcare where regional specialisation of treatment centres can result in higher care standards for patients

The Medicines Evaluation Board (MEB), the agency responsible for issuing marketing authorisation in the Netherlands, has stated that a single treatment centre was “very vulnerable… in the event of a failure treatment centre there are no alternative centres”. The MEB recommended the establishment of additional treatment centres but given the complexity of the manufacturing process for many ATMPs, and the requirement for specialisation in ultra-orphan conditions, this is often neither feasible nor desirable. Engagement with European Reference Networks (ERNs) can provide a rationale for the need for single treatment centres and reassure authorities in the Netherlands about access to clinical expertise. It is also possible that within the ERN network ‘fall-back’ processes could be explored to provide support to any country where a local problem arises. Similarly, assurance should be provided to assessors in the Netherlands on highly regulated manufacturing processes of ATMPs which ensure consistency of quality and supply.

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