Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years’ multi-stakeholder dialogue on improving access in Europe via MoCA

doi:10.21203/rs.3.rs-2692814/v1

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Research Article

Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years’ multi-stakeholder dialogue on improving access in Europe via MoCA

https://doi.org/10.21203/rs.3.rs-2692814/v1

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published 12 Jun, 2023

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Background: The Mechanism of Coordinated Access to orphan medicinal products (MoCA) was established in 2013 with the intention of developing a coordinated mechanism between volunteering EU stakeholders and developers of Orphan Medicinal Products (OMPs) to support the exchange of information aimed at enabling informed decisions on pricing and reimbursement at Member State level and to evaluate the value of an OMP based on a Transparent Value Framework. The objective of the collaborative approach was to support more equitable access to authorised therapies for people living with rare diseases, rational prices for payers and more predictable market conditions for OMP developers. Over the past 10 years, the MoCA has conducted a series of pilot projects, examining a variety of different products and technologies at different stages of development; and with contributions from a variety of patient representatives, participation from EU payers from a range of Member States; and, recently, with EUnetHTA members and the EMA participating in the meetings as observers.

Results: 10 years on from the establishment of the MoCA, the European landscape has significantly evolved, not only in the field of drug development with increasingly transformative therapies based on novel technologies, but also in terms of larger numbers of approved treatments, increased budget impact and the resulting associated uncertainties; as well as in terms of stakeholder collaboration and interactions. The value of early dialogue with OMP developers, including the EU payer community via their national decision-making authorities, is a key element within this early interaction and contributes to identifying, managing and reducing uncertainties allowing a prospectively planned approach earlier in development and, consequently, to support more timely, sustainable and equitable access to new OMPs, particularly where there is a high unmet medical need.

Conclusions: The voluntary, informal nature of the MoCA interactions creates a flexible framework for non-binding dialogue. A forum for such interactions is needed to achieve the aims of the MoCA and to support both healthcare systems in planning as well as to underpin timely, equitable and sustainable access for patients with rare diseases to new therapies within the EU.

access to medicines

orphan medicinal products

multi-stakeholder

early dialogues

The Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA) was established as part of the “Process on Corporate Responsibility in the Field of Pharmaceuticals” (1) launched by the European Commission (EC) in September 2010 to examine a range of issues, including the evaluation of non-regulatory conditions to support better access to medicines following European Union (EU) Marketing Authorisation.

The Process on Corporate Responsibility consisted of three pillars: (1) Transparency and ethics in the sector; (2) Access to medicines in Africa; and (3) Access to Medicines in Europe, notably in the context of national pricing and reimbursement decisions that ultimately determine the real availability of novel therapies to patients. The third pillar was sub-divided into different working groups, one of which focused on access to Orphan Medicinal Products (OMPs) within the EU. The “Mechanism of Coordinated Access to Orphan Medicinal Products” (MoCA) was tasked with examining the potential contribution of increased collaboration between EU Member States (MS), decision-makers and stakeholders in supporting the timely, sustainable, and equitable access to novel OMPs and treatments for rare diseases within the Union. In its original form, MoCA was intended to map innovative ways to provide real-life access to OMPs in an affordable and sustainable way for patients with unmet medical needs for whom these solutions would otherwise be out of reach: real access to a real solution for real patients with real unmet medical needs (2).

The main recommendation of the MoCA outcomes was to develop a coordinated mechanism between volunteering EU Member States and developers of OMPs to examine and evaluate the potential value of an orphan medicinal product, based on a collaboratively developed Transparent Value Framework (TVF). The objective was to support the exchange of information in a structured format, aimed at enabling informed and data-driven decisions on Pricing and Reimbursement (P&R) at Member State (MS) level. The participants believed that such structured dialogue, ultimately, would lead to more rational prices for payers, more predictable market conditions for industry and more equitable access for patients(2).

Following the 2013 conclusions and reporting from the Process on Corporate Responsibility in the Field of Pharmaceuticals, key members from the Mechanism of Coordinated Access to Orphan Medicinal Products Working Group agreed to further pursue discussions to explore operationalising the recommendations under the umbrella of the Medicines Evaluation Committee (MEDEV), a working group of experts from statutory health insurance institutions and Health Technology Assessment (HTA) agencies in Europe, operating under the auspices of European Social Insurance Platform (ESIP) since 1998. The objective was to explore the feasibility of putting the MoCA conclusions and recommendations into practice through the implementation of pilot projects focused on real OMPs in development. Following the establishment of the first pilots, the MoCA published its revised terms of reference in 2016 (3); and EURORDIS agreed to host the MoCA webpage (4) to gather the main information for potential applicants. In 2018 the European Medicines Agency (EMA) and EUnetHTA initiated participation as observers in the pilot projects and in 2020 MoCA shifted from in-person to online meetings as standard operating procedure due to the global COVID-19 pandemic. This enabled a broader participation from a larger number of different Member State payer authorities as well as an increased number of experts from other stakeholders, further increasing the value of the MoCA dialogues.

The TVF lists the elements which are important criteria contributing to the value of a new OMP: 1) available alternatives/unmet need (including non-pharmaceutical treatment options); 2) the relative effectiveness/degree of net benefit relative to alternatives (including no treatment); 3) incremental/major/curative response rate (based on best available clinically relevant criteria); and 4) degree of certainty. Specifically, the TVF is an instrument for supporting increased transparency of the relationship between value and pricing by defining the criteria of value to payers in a qualitative and semiquantitative manner. The TVF is based on the consensus between various stakeholders in the working group of the Process on Corporate Responsibility on how to assign value in a consistent way and, as such, was considered a relevant framework to support collaborative dialogue, by providing a structure in a consistent way, to ensure equal treatment of patients and providers across the wide range of OMPs and technologies (2).

Table 1: Adapted from the Transparent Value Framework (2)

Criterion	Lower Degree	Medium Degree	High Degree
Available Alternatives/ Unmet Need, including non-pharmaceutical treatment options	Yes, new medicine does not address unmet need	Yes, but major unmet need still remains	No alternatives, except best supportive care - new drug addresses major unmet need
(Relative) Effectiveness, Degree of Net Benefit (Clinical Improvement, QoL, etc. vs. side effects, societal impact, etc.) relative to alternatives, including no treatment.	Incremental	Major	Curative
Response Rate (based on best available clinically relevant criteria)	<30%	30-60%	>60%
Degree of Certainty (Documentation)	Promising but not well-documented	Plausible	Unequivocal

The dialogue in MoCA over the past decade extended beyond the initial framework of analysing support for decisions on P&R, which remain the exclusive competence of each EU Member State. Despite the national competency and responsibility, EU Member States share the principles of equity and solidarity; face common challenges in providing diagnosis, treatment, and care for patients; and share similar financial and organisational burdens in organising access to novel and often costly therapies. All of these challenges are rendered more acute in the case of rare diseases and OMPs, where small numbers of patients are concerned; where expertise is scarce and scattered and where potential therapies to address the unmet medical need are increasingly based on emerging technologies and may engender significant economic considerations, including uncommon or new dosing regimens, as is often the case with cell- and gene-therapies.

Despite the contribution of the EU Regulation on Orphan Medicinal Products (Regulation (EC) No 141/2000) over the past 2 decades and the effective overall EU policy framework to support the development and authorisation of OMPs and new treatments for people with rare diseases, delays and disparities in accessing therapies for rare disease patients are still being reported (5).

Against this background, stakeholders including Member States, patients’ organisations, the pharmaceutical industry, competent authorities on pricing and reimbursement (‘payers’), HTAs and Regulators have recognised the importance of early and cross-functional engagement in a unique forum including payers to improve a shared goal of improving timely and equitable access to authorised OMPs in a coordinated manner.

The MoCA Steering Committee, together with participating payers, patient community and company representatives has reviewed the experience gained from the pilots to capture and evaluate the benefits for different stakeholders in terms of facilitating the shared goal of timely, equitable and sustainable access to OMPs within the EU provided by the early collaborative dialogue in MoCA.

10 years of experience of MoCA

During the 10 years since the establishment of MoCA, the medicine development landscape has significantly evolved (e.g., with the introduction of gene-, cell- and other transformative therapies) and, in addition, so have the corresponding challenges in evaluating potential therapies and reaching decisions on reimbursed access. In the past decade the HTA network, EUnetHTA, has become increasingly formalised, evolving from its initial informal collaboration to the current structure under the new EU HTA Regulation (6). This has allowed the EUnetHTA and its members to increasingly collaborate to address the gaps in evaluation of novel therapies that have been identified over the years as technologies have evolved. The EMA has not only established increasingly structured and formalised dialogues with EUnetHTA including, most recently, the Joint Scientific Consultation pilot projects announced in 2021 and having a second round in 2022-2023 (7); but also, with the payer community under the European Medicines Agency and Payer Community meetings initiated in 2017 (8), the second meeting in 2019 (9) and the most recent in 2021 (10).

Individual country frameworks are evolving to accommodate more inclusive evaluations, being HTA or P&R discussions. Also, an increasing number of Member States payer authorities are evaluating the benefits of cross-border collaboration further downstream, including the BeNeLux-I-A (11) and FINOSE (12), amongst others. The value of collaborative dialogue is, therefore, acknowledged by a broad range of stakeholders within the evaluation and reimbursement of novel therapies. MoCA uniquely offers such collaboration with all stakeholders from earlier stages of development, allowing feedback to be included both in a potential clinical development programme and post-authorisation activities.

Initially, MoCA meetings were held in person following the regularly scheduled MEDEV meetings. During the COVID-19 global pandemic, the MoCA meetings shifted to an online platform, which brought unanticipated advantages for all stakeholders by facilitating broader participation on a more consistent basis: for the volunteering rare disease patient representatives, who previously were not always able to participate in face-to-face meetings due to issues with travelling and/or other time commitments; for the payers, because they could recruit experts who were not foreseen to be participating in the MEDEV-ESIP meetings; and for the companies because the online meeting format reduced travel costs and allowed participation of a broader representation of expertise directly involved in the clinical development programme.

Since MoCA was established, 47 meetings have taken place on a voluntary basis, within the framework of a non-legislative, non-regulatory and non-binding collaboration among stakeholders who are willing to work together to support real access to a real solution for real patients with real unmet medical needs. In total, MoCA has accommodated 16 companies and discussed 23 different products (Table 2) along different stages of the development (Table 3) and Anatomical Therapeutic Chemical (ATC) classification (Table 4). 20 patients’ representatives have participated, some of them participated in more than one meeting. 12 of the products discussed were small molecules, 5 biologicals and 5 advanced therapies, and one therapeutic approach was classified as “other” (Table 3).

The topics discussed during the meetings include, amongst others, the epidemiology of the condition in question and the definition of the patient population most likely to benefit; the relevance of endpoints selected by the regulators and the demonstration of potential added value by the product; the needed data requirements prior to initial reimbursement as well as post-authorisation and how and when these can be collected; and potential novel payment models. The authors recognise that discussions around specific pricing are very sensitive for all stakeholders involved, and the MoCA is not intended to accomplish this. However, the MoCA offers an opportunity to discuss potential parameters for managed entry agreements. The MoCA provides a unique multi-stakeholder setting because all the stakeholders are represented: patients, payers, company representatives, regulators and HTAs. Other platforms exist that allow exchanges between a subset of stakeholders; the MoCA is the only platform that brings all participants together at the same time and around the same questions, which allows a full exchange of opinions addressing all the relevant points in one setting.

Statistics:

Table 2. MoCA meetings and participation (09/2013 – 12/2022)

Total Number of Meetings	47
Meetings per Company	Average: 2.9/ Median: 2/ Maximum: 9
Meetings per product	Average: 2.04/ Maximum: 6
Number of OMP developers participating /consortia	16
Number of products discussed	23
Number of patients representatives	20
Number of payer-representing institutions that attended at least 1 meeting	27
Other participating institutions: ESIP and Academia, as well as EMA and EUnetHTA as observers

Table 3. Development stage of the products

Status at first contact	Number	Status as of 20 Feb. 2022
Pre- clinical stage	3	2 in development, 1 terminated
Phase 1/2	4	1 in Phase 3, 1 authorised, 2 terminated
Phase 2	4	1 authorised, 1 in Phase 3, 2 terminated
Phase 3	7	3 authorised, 1 under evaluation by EMA, 2 in Phase 3, 1 terminated
Marketing Authorisation Application submitted	2	Both authorised
Already authorised in the EU	3	1 withdrawn, 1 off-patent, 1 marketed but not orphan

Table 4. Anatomical Therapeutic Chemical code (ATC) classification of products

ATC	Number of products
A(limentary)	5
B(lood)	4
C(ardiovascular)	3
(Onco)L(ogy)	2
M(usculoskeletal)	3
N(ervous system)	3
R(espiratory)	2
S(ensory)	1

Benefits for participating stakeholders

Stakeholders have highlighted the benefits of MoCA meetings because of its nature as a unique forum where all stakeholders are present, as mentioned above. Patient engagement in multi-stakeholder dialogue is essential, particularly in the field of rare diseases where expertise is scarce and scattered and, very often, the people affected by a rare disease are the best source of such expertise in their specific condition. The multi-stakeholder exchanges incorporating all decision-makers are a valuable opportunity to not only improve awareness of the diseases, diagnostic and treatments; but also to identify and discuss potential barriers to access; increase affordability; improve cost-effectiveness by improving the evidentiary base and to develop innovative and practicable payment models to support actual access to new therapies in a timely and sustainable manner, often against a backdrop of lack of existing therapeutic alternatives.

Having a multi-stakeholder framework to bring together what could be otherwise fragmented data collection exercises has the potential to enhance the quantity, quality and relevance of gathered data. Utilising the opportunities provided by the EU collaboration could create knowledge relevant to informing understanding of given rare conditions in other jurisdictions and geographies.

Patients representatives

For the patients, MoCA meetings are a “safe space” to share their experience of living with the condition under discussion, to better understand the potential contribution of new therapies and to outline their expectations towards the new treatments. During these meetings, better and coordinated follow-up and discussion of patient reported outcomes (PROs) and real-life experiences helps developers of OMPs to tailor the clinical trial design.

Having patient representatives participating in the meeting and providing their real-life experience of living with the condition can also be a significant added value because the discussion of unmet need can be more holistic and can encompass real-life experience of the impact of a given rare disease.

For the payers, regulators, and developers MoCA provides an opportunity to hear from patients and their needs. All patients involved in these meetings sign a declaration of interests and a confidentiality agreement to ensure transparency and comply with the MoCA internal procedures.

EURORDIS manages the process for involving the patient representatives at all stages of the process, from the first identification of the participants best suited to cover the perspectives on the specific rare disease in question to be addressed in the meetings; and actively mentors them through the process. Patient representatives participating in MoCA meetings have highlighted the value of the early dialogues, one participant commenting that “cooperation with all stakeholders must be more intensive and this kind of meeting must be held on a regular basis”.

Payers

For the payers, MoCA is an opportunity to prepare in advance more informed decisions on treatments for diseases about which, not much may be known. Within one setting, valuable discussions can be held on a range of different elements that have a direct impact on national healthcare decision-making, including patient (sub)populations, posology, alternative treatment options, possible budget impact, organisational aspects and cross-border care, in the context of a given rare disease. Payers are better able to assess how far the new technology addresses real unmet medical needs from the direct engagement of patients living with the disease in question. The potential exists to speed up reimbursement decisions when payers’ evidence requirements are met. MoCA also offers an opportunity to prepare for the post-launch evidence generation plan, in cases where a Marketing Authorisation has been or is expected to be granted on the basis of a limited level of evidence, which is often the case for OMPs and rare diseases. Such authorisations increase uncertainty on the value of the new technology as compared to alternatives (if existing) and, as such, having a prospectively designed plan to develop evidence to support pricing and reimbursement decisions on a longer term is an important element for healthcare systems.

Another key outcome is the trust and mutual understanding between payers and the OMPs developers’ through not only the MoCA dialogue itself but also afterwards in the actual national P&R processes. Early dialogue allows a more prospective, rather than reactive approach; and creates the possibility to anticipate potential requests that would otherwise not been expected. The early opportunity to address payers’ needs is one of the key elements of added value provided by MoCA because in other settings, e.g., the EMA-EUnetHTA dialogues, payers are not included, which can result in additional and unanticipated requirements are requested by payers at a later stage.

OMP developers

For OMP developers, the MoCA pilots have provided numerous benefits at all stages of development. In early phases, the benefits include the possibility to gain early payer input on a clinical trial programme and the potential resulting reimbursement dossier and, in addition, to be able to explain the unmet need for conditions that could be less known to payers. The MoCA process helps to clarify questions early on in the development programme, e.g., acceptance of endpoints, expected comparators, perceptions of conditional marketing authorisation, evidence generation both pre- and post-authorisation; and has helped guide strategies to address data gaps, e.g., through a registry strategy. The TVF, while providing criteria for evaluation at a high level, creates a structured format for discussing the scientific value of a novel therapy and its potential place in healthcare systems.

Having the opportunity to explore the epidemiology and heterogeneity of a given condition and potential subsets of severity; together with the willingness to treat and the expected treatment outcomes are critical elements in a future request for coverage. Reviewing the Target Product Profile and the eventual anticipated label at an early stage in a multi-stakeholder setting is a critical element around understanding potential patient numbers and forecasting, both for developers and healthcare systems. Further, where rare diseases have had no therapy to date and might, therefore, be “invisible” to the pharmaceutical budget holders, allowing sufficient time to explore clinical benefits and impacts of a potential new therapy are important.

For OMP developers, the MoCA platform provides a unique opportunity to hear feedback from a group of ‘real payers’. MoCA provides access to a group of decision-makers actively involved in the assessment and decision-making for novel therapies. Traditional platforms such as Payer Advisory Boards have an important role to play; but at the same time these differ from MoCA because they tend to include proxy or ex-payers who, while having extensive experience, might lack the latest nuances of a given country authority. Payers participating in MoCA as part of their actual work mean that they are likely to be fully engaged with a dossier that is “live” for them. Under the payers’ employment contracts, the dialogue is conducted subject to the same levels of confidentiality that would be the case in a regular “one on one” engagement with a national P&R authority.

Having the patient perspective included at the same table with the payers and other decision-makers allows for a more impactful description of the challenges of living with a given rare disease – something which a developer alone would struggle to be able to portray accurately and, in a way, relevant to the national decision-makers. Some OMP developers observed that it was “only when payers heard the perspective of the patient representative did they really understand the challenges in the current standards of care and the value that a novel therapy could bring”.

Discussing the clinical trial protocols to better understand perceived data gaps by payers has also helped a number of companies develop a registry or evidence-generation strategy early on to address these gaps. Having an early dialogue can encourage all stakeholders to come closer together on their position and to identify data gaps early on to accelerate negotiations once these become live. Post-launch data collection requirements are currently progressed with each individual data customer individually.

Using the TVF as the basis to achieve a “common language” has also proven a valuable exercise that can facilitate individual company decisions. For example, one company shared that, “following the discussion with MoCA we made a concession on price in order to ensure faster access to the treatment across Europe. At the same time, the payers in the room had a better understanding of the value of the therapy and we believe this helped with negotiations in a number of countries”. In other negotiations, understanding the reality of pricing allowed companies to enter into discussions to revise existing prices, based on transparency and trust established in the MoCA engagements.

Some elements could make the MoCA even more productive for companies seeking to launch a rare disease therapy in the EU. The main challenges companies face in participating in MoCA relate mainly to the historical inconsistency in terms of participation and discussion at the different meetings. As a voluntary initiative, it is not to be expected that all payers from the 27 EU Member States participate in all MoCA meetings. However, the uncertainty about the number of participants can be a deterrent for companies, which invest significantly in the preparation of the discussions. Some companies participated in MoCA meetings with more than ten country representatives, while others only had two. The online participation following the COVID pandemic has contributed to increasing consistent levels of participation. Having a minimum threshold of participants for the meeting to go ahead would help support consistent engagement by developers of OMPs. Similarly, having budget or resources to secure a full-time hire who can manage the agenda and encourage participation by MS authorities would be useful. Having neutral support, i.e., not the company concerned, in highlighting to the participating country payer authorities if there is an aspect of particular relevance, e.g., the presence of a clinical trial being conducted in their country; or a specific centre of expertise, would be an added value to allow effective evaluation and decisions about participation from MS’ authorities.

Regulators and HTA

The EMA as the major European regulatory body is committed to enabling timely patient access to new medicines and plays a vital role in supporting medicine development for the benefit of patients. Orphan Medicinal Products are obliged to follow the Centralised Procedure, with the objective of supporting equitable access to needed therapies for rare diseases within the EU.

Pricing and reimbursement issues are not the competence of EMA. In fact, EU regulation stipulates that “in the interest of public health, authorisation decisions under the centralised procedure should be taken on the basis of the objective scientific criteria of quality, safety and efficacy of the medicinal product concerned, to the exclusion of economic and other considerations” (13). However, the definition and optimisation of treatment-eligible population(s), accurate description of expected clinical benefits and potential harms, identification of knowledge gaps, and ensuring that relevant knowledge gaps are closed by post-licensing evidence generation, are core responsibilities of the EMA – as is communication of these issues to external stakeholders. The EMA has rightly understood that HTA bodies and payers are among the most interested, knowledgeable (and sometimes most critical) “customers” of their decisions and communications. Therefore, the EMA has been interested in participating and supporting dialogues with and between payers/HTA and companies developing OMPs before a potential Marketing Authorisation is granted, for example in the context of the EMA/payers meetings (8,9,10) Requirements from payers and HTA-bodies can be integrated in the early dialogues of the regulator in early advice on the design of Phase 3 clinical studies. The EMA will also be able to explain to national payers and/or HTA bodies the reasons why the new product might be assessed to have a positive benefit-risk-ratio. These considerations can be taken into account in the assessments of the HTAs and payers when reflecting the additional benefit to the current standard of care of the new product. Further alignment on post-launch evidence generation to maximise available data to support decision-making on safety, efficacy and effectiveness will be an important opportunity, particularly in the field of rare diseases and OMPs where patient numbers are limited and where cross-function and cross-border EU collaboration can add value at an EU but also potentially at a global level. Therefore, EMA’s participation in MoCA as observers is well justified and valuable.

Importantly, the Regulation on Health Technology Assessment (6) (“the HTA Regulation”) was adopted in December 2021 and introduces a permanent legal framework for joint HTA at European level. The Regulation aims to provide for a mechanism that ensures that any information, data, analyses and other evidence required for the Joint Clinical Assessment (JCA) should be submitted only once at the EU level by the health technology developer.

It will cover Joint Clinical Assessment (JCA) as well as Joint Scientific Consultations (JSC) with health technology developers to provide consultations in particular in concerning all relevant clinical study design aspects, or clinical investigation design aspects, including comparators, interventions, health outcomes and patient populations.

While the HTA Regulation for medicinal products with new active substances for oncological indications and advanced therapy medicinal products (ATMPs) (i.e., gene, tissue, and cell therapy products) will be implemented from 12 January 2025, the HTA Regulation’s application will extend to orphan medicinal products from 13 January 2028 and from 2030 to all centrally authorized medicinal products.

These changes may well affect the work of MoCA, making it useful as a low-threshold, informal “entry point” for companies to discuss their products at an earlier stage on a multi-stakeholder platform, and to coordinate their interactions with agencies and various competent authorities, with patient input.

Table 5. Summary of the Potential and Realised Benefits of MoCA as a Multi-Stakeholder Approach in Europe

COMPANIES	REGULATORS	HTA	PAYERS	PATIENTS
Payers input early enough to support a clinical development programme adapted for downstream decision-making.	Insight into potential “downstream” problems impacting anticipated availability, opportunity for direct interaction with HTAs and payer, i.e. some of the regulators’ key customers of information.	Enhanced awareness of the condition and the actual unmet medical need to support potential future comparative assessments.	Better budget impact awareness and predictability; insights into potential treatment-eligible population(s), epidemiological data; opportunity for early understanding of treatment setting or pathways (e.g., hospital vs. outpatients setting, first or later line therapy…)	Quicker and broader availability of an individual OMP / rare disease therapy; increased equity across EU Member States.
Increased predictability and planning for launch timing, likely uptake, barriers.	More efficient Scientific Advice (if advice is taken into account).	Better data for HTA (if advice is taken into account).	Unique platform for multi-stakeholder and multi-country engagement on an individual OMP / rare disease therapy; opportunity to discuss potential parameters for managed entry agreements.	Better understanding of needs and expectations from decision-makers in determining access and availability questions.
Clear understanding from all data-customers about data-requirements to support value demonstration, initial pricing & reimbursement decisions and maintenance.	Input into consolidated post-authorisation data-collection in conjunction with other data-customers – avoiding fragmentation and supporting inclusion of EMA tools (14) including Guidance and link with EUnetHTA / HTA tools, e.g., REQqueST (15).	Dialogue that includes the payer / budget-holder perspective on a given product/therapy, especially for countries where the HTA / payer agencies are split.	Sharing of expertise with different Member States / transparent understanding of clinical value, natural history, and related organisational aspects.	Ability to inform and engage with OMP developers to secure relevant endpoints / expectations and needs are included.
Guidance on prospectively designed post-marketing evidence generation / data-gathering / requirements based on gap identification from all data customers from earliest phases of development / market launch planning.	Secure HTAs and Payers are aware of the (regulatory) rationale for decisions on endpoints and their relevance to the therapeutic area in question.			Better, coordinated follow up and collection of PROs and real-life experience.

[Insert Table 5. Summary of the Potential and Realised Benefits of MoCA as a Multi-Stakeholder Approach in Europe]

Remaining challenges

During the 10 years since the establishment of the MoCA, science has evolved significantly with new classes of transformative therapies becoming available for the first time. While offering potential benefits in a variety of conditions, these evolutions have, at the same time, created an increasingly complex environment with high uncertainties, often high prices in an environment of healthcare budget constraints and the global COVID-19 pandemic; and have highlighted the need for early dialogues with all stakeholders involved in decision-making that potentially could help to solve some of these issues. As an example, MoCA multi-stakeholder exchanges are an opportunity to identify and discuss potential barriers to access and to discuss the expected added benefit to a comparator and if significant uncertainties are identified MoCA provides a forum where payers can reflect how these uncertainties can be addressed in payment models.

MoCA is not an opportunity to “pitch the product”; and is not a “cure-all” solution – it is not the overarching forum that will solve all challenges, but it is, at a minimum, an opportunity to frame the questions and to support an early understanding of downstream needs from decision-makers via a flexible, multi-stakeholder platform, that is independent, informal and free of charge, playing a key role in coordinating the input from key stakeholders. The informal aspect has been key to translate the MoCA advice into national reimbursement processes for each EU Member State separately, respecting different national and agency competences, and has underpinned engagement downstream as well as allowing input from upstream.

Based on the learnings from the past decade, the authors are aware that resources would be needed for further engagement, to support more structured dialogues, while keeping MoCA’s flexibility and independence. Rare diseases patient representatives need to be involved beyond the time of Marketing Authorisation. Better alignment with other processes, such as Scientific Advice and the EMA-EUnetHTA consolidated Scientific Consultations and the EMA-Payer Community forum is needed, particularly on key questions of evaluation and assessment. Payer participation should be encouraged and supported by national authorities.

For developers of OMPs, more guidance on when, where and how to approach MoCA is will be of benefit. Many companies, particularly Small- & Medium-sized Enterprises (SMEs) might find it challenging to differentiate between MoCA and the variety of existing initiatives – from EMA’s Scientific Advice, with or without HTA input, to the dialogue with regional consortia, such as BeNeLux-I-A and FINOSE. Highlighting the informal and inclusive nature of the MoCA opportunity should be an important element to explore.

Next steps: Strategic Learnings for the Future of MoCA?

MoCA is a free-of-charge, voluntary platform based on collaboration and goodwill between participants to explore opportunities to address shared challenges in securing real access to real therapies for real patients with rare diseases. Based on more than 10 years’ experience, participants have identified a set of clear benefits for all stakeholders involved, contributing to the original stated objectives of supporting timely, sustainable and equitable access to novel therapies for people living with rare diseases. However, in order to secure sustainability beyond the individuals who have been leading and coordinating the voluntary platform, the authors believe that now is the time to establish a more solid organisational footing for the dialogue, including adequate resources; and to support processes for the sustainability of MoCA and its meaningful work in the longer term. Given the added value at a Community level to support the EU goals of equitable access to novel therapies, the authors believe that an EU Joint Action would be an appropriate vehicle to provide funding in order to build on the work conducted over the past 10 years as well as to further develop a robust and sustainable multi-stakeholder platform for early dialogue as discussed in the second EMA-payer community meeting in 2019.

Future involvement of the European Reference Networks (ERNs), the continued involvement of the EMA and EUnetHTA as key stakeholders, in addition to the payers and the patient community, all of them with a stronger mandate to align on key questions of evaluation and assessment would ensure effective, timely, broader and meaningful input from all implicated stakeholders; and would, at the same time, contribute significantly to speeding up patient access to needed therapies while supporting increased equity across European Member States. The body of knowledge developed in an individual condition or therapeutic area by a cross-functional, cross-border collaboration could also give rise to datasets or learnings that could add value to the international rare disease community beyond the EU borders.

On the basis of the 10 years of valuable experience generated by the MoCA pilots, the authors believe that it is now time to move to the establishment of a permanently supported platform, which would save and optimise payers resources as well as allowing for a structured collaboration between competent authorities to assess the value of OMPs and to support the negotiation of fair and equitable prices on a European scale in exchange for an earlier, if not immediate, access to patients across Europe, multi-year buying commitments and revenue predictability for developers of OMPs and rare disease therapies. A coordinated, European plan on the basis of input from all decision-makers could address the uncertainties at the time of Marketing Authorisation for many OMPs, by providing a plan to develop additional evidence to reassess the value of a product at an agreed time point.

MoCA is a unique platform providing informal and confidential, but structured early dialogue between all stakeholders and, as such, offers the potential to become a permanent structure; and a potential solution for the accessibility, availability and affordability challenges that has been identified in the field of OMPs and rare diseases.

Mechanism of Coordinated Access to orphan medicinal products (MoCA)

Orphan Medicinal Products (OMPs)

Transparent Value Framework (TVF)

Member State (MS)

European Comission (EC)

European Union (EU)

Health Technology Assessment (HTA)

Joint Scientific Consultations (JSC)

Pricing and Reimbursement (P&R)

Medicines Evaluation Committee (MEDEV)

European Social Insurance Platform (ESIP)

European Medicines Agency (EMA)

Quality of Life (QoL)

Anatomical Therapeutic Chemical (ATC)

Patient Reported Outcomes (PROs)

Joint Clinical Assessment (JCA)

advanced therapy medicinal products (ATMPs)

Small- & Medium-sized Enterprises (SMEs)

European Reference Networks (ERNs)

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors have approved the manuscript for submission. The content of the manuscript has not been published or submitted for publication elsewhere.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available due to the confidential nature of the MoCA discussions.

Competing interests

The following authors have no conflict of interest to disclose: Maria Cavaller-Bellaubi, Šárka Kubinová, Evert Jan Van Lente, Marc Van De Casteele, Johan Pontén, Yann Le Cam, Simone Boselli, Anna Bucsics, Hans-Georg Eichler. Wills Hughes-Wilson is employed by Mereo BioPharma plc and holds shares in this company as well as other biopharmaceutical companies. Emanuele Degortes is employed by the Menarini Group.

Funding

The financial support of MoCA by Zorginstituut Nederland (ZIN) and Rijksinstituut voor Ziekte- en Invaliditeitsverzekering (RIZIV-INAMI) between 2016 and 2019 is gratefully acknowledged.

Authors’ contributions

MCB, WHW, AB, SK, MVdC, EJvL, JP, SB were involved in the conception of the manuscript. AB and SK were involved in collecting the data and producing the tables. MCB, WHW, AB, SK, MVdC, EJvL, JP, SB, ED, YLC and HGH were involved in the writing of the manuscript.

Acknowledgements

The authors want to thank Francis Arickx, Ri de Ridder and Ad Schuurman for their significant contributions to the MoCA.

Authors information

Maria Cavaller-Bellaubi: [email protected]

Wills Hughes-Wilson: [email protected]

Šárka Kubinová: [email protected]

Marc Van De Casteele: [email protected]

Evert Jan Van Lente: [email protected]

Emanuele Degortes: [email protected]

Johan Pontén: [email protected]

Hans-Georg Eichler: [email protected]

Yann Le Cam: [email protected]

Simone Boselli: [email protected]

Anna Bucsics: [email protected]

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published 12 Jun, 2023

Read the published version in Orphanet Journal of Rare Diseases →

Editorial decision: Major revision
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Reviewers agreed at journal
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Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years’ multi-stakeholder dialogue on improving access in Europe via MoCA

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