Rare diseases (RD) are conditions that affect a small number of people, usually about 1 to 5 out of 10,000, its definition varying depending on the country. For example, in Thailand, a RD is defined as any disease that affects a small percentage of the population, no more than 10,000 in the country, while in Taiwan, a RD is defined as being prevalent in less than 1/10,000. RD affects an estimated 258 million people in the Asia Pacific region in 2020, with 50% of those affected being children1https://www.cslbehring.com/vita/2020/rare-diseases-in-asia-pac-infographic. An inherent challenge for a disease affecting only a tiny percentage of the population is that there are more complex funding and access barriers than for common diseases. Rare diseases have been especially challenging to manage in Asia Pacific because of the socioeconomic disparities across the region and the lack of research, expertise, and health policies for rare disease patients. However, the collective challenge of rare diseases has risen up the policy agenda in Asia Pacific with various new and revised health and social system measures in Australia, Japan, South Korea and Taiwan – along with the 2018 Asia Pacific Action Plan – reflecting a growing recognition of the need to take action.
By connecting drug reimbursement to the drug’s actual efficacy or linking the sales to a certain volume, Managed Entry Agreements (MEAs) have gained attention as a viable solution to access problems in Asia Pacific. In this article, Alcimed explores the feasibility of MEAs and its potential to enable access to rare disease treatments in Asia Pacific.
Conceptually, the foundation of MEAs is a two-part agreement addressing the burden of cost and price along with uncertainties in benefit. Often, MEAs are used by payers as cost containment tools, allowing them to stay within their allocated budgets.
Although the terminology and definition of MEAs continue to evolve, the World Health Organization for Economic Cooperation and Development has defined MEAs as an “arrangement between a manufacturer and payer/provider that enables access to (coverage or reimbursement of) a health technology subject to specified conditions. These arrangements can use a variety of mechanisms to address uncertainty about the performance of technologies, manage the adoption of technologies to maximize their effective use, or limit their budget impact1https://www.cslbehring.com/vita/2020/rare-diseases-in-asia-pac-infographic.”
There are two main types of MEAs, namely Financial-based agreements (FBAs) and Outcome-based agreements (OBAs).
FBAs refer to an agreement in which the payment for a treatment is based on the financial outcomes of the therapy, such as the number of patients treated or the duration of the treatment. There are typically three variations of FBAs: expenditure cap, volume cap, and refund type. One of the medicines listed through the FBA refund contract in South Korea is Galsulfase, which is currently the only Enzyme Replacement Therapy indicated to treat patients with MPS VI (Maroteaux-Lamy Syndrome). In South Korea, from 2014 – 2020, approximately 98% of the MEAs implemented for 48 listed medicines for cancer and rare diseases consisted of a form of FBA2https://doi.org/10.1371/journal.pone.0182613 . However, it is noteworthy that FBAs may provide an advantage to larger, wealthier markets and put a disproportionate burden on smaller, less wealthy markets as manufacturers may be more inclined to establish FBAs when negotiating with payers from larger markets with higher purchasing power parity.
On the other hand, OBAs focus on the actual clinical outcomes of the treatment, such as an improvement in disease symptoms or a reduction in hospitalization rates. In this approach, payment for the therapy is linked to the treatment’s ability to achieve the desired clinical outcomes. By linking payment to clinical outcomes, payers can be more confident that they are paying for treatments that deliver meaningful benefits to patients. Pharma companies may also use OBAs as a strategy to demonstrate the value of their therapies in APAC markets. For example, in July 2022, South Korea approved a one-time intravenous injection of Zolgensma® (onasemnogene abeparvovec-xioi), the only one-time gene replacement therapy to treat SMA (Spinal Muscular Atrophy), a rare neuromuscular condition. The drug is considered one of the most expensive in the world, costing $2.1 million for a single treatment. Under the agreement, Novartis will return a set proportion of the cost in the event of treatment failure3https://doi.org/10.1186/s12913-021-06919-x. OBAs can also allow for periodic re-evaluation and adjustment of reimbursement criteria based on real-world outcomes.
Despite MEAs becoming increasingly common in the EU and American markets, there has been evidence of sporadic implementation in Asia Pacific markets, particularly in South Korea and Taiwan, with evidence of success. In South Korea, deployment of MEAs has benefitted at least 15,000 patients with early access to new drugs, especially in oncology and rare diseases, such as Galsufase, Eculizumab and Lenalidomid4https://doi.org/10.6288/TJPH.202208_41(4).111015. In Taiwan, since the deployment of MEAs in 2018, approximately 77 drugs have been submitted for MEA, of which over 70% are drugs for malignant neoplastic diseases and immunomodulating agents5https://doi.org/10.1016/j.vhri.2020.07.138 . There has been almost no uptake of MEAs in the Association of Southeast Asian Nations (ASEAN) so far, but ALCIMED sees some early signs that this may change.
In 2023, research conducted in Thailand also concluded that a financial-based MEA framework may be a promising solution to address the inherent challenges of limited and delayed access to high-cost innovative treatments in Thailand and broaden coverage of medicines to vulnerable populations6https://doi.org/10.3389/fphar.2023.999220.
Although the implementation of MEAs could potentially resolve the economic burden of rare disease medicine and improve access, the implementation of MEAs across Asia Pacific markets can be challenging for several reasons7https://www.koreabiomed.com/news/articleView.html?idxno=14205:
Asia Pacific has a wide diversity of healthcare systems and legislation. When it comes to implementing outcome-based contracting across borders, this variation might pose issues. This is exacerbated by the lack of a unified definition for rare disease and the true burden of many rare diseases in APAC being yet undefined. Steps in the right direction have been taken through the development of the APEC Action Plan on Rare Disease, formed in 20198https://www.himss.org/resources/apac-value-based-care-government-roundtable-report but implementation remains a challenge.
More specifically for OBAs, data infrastructure is required to monitor patient outcomes over time and be able to show clinical benefits. As such, a proper data infrastructure is required to gather and maintain patient data to ensure that all parties participating in the agreement have access to accurate and up-to-date patient outcome information. Unfortunately, many Asia Pacific markets may lack the digital infrastructure needed to properly store and analyse data.
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Low awareness of rare diseases among healthcare professionals in the Asia Pacific region, suggests that stakeholders may prioritise addressing more common diseases with broader population impacts, leaving rare diseases under-recognised and under-funded. Low awareness also means that there are fewer patient advocacy groups and experts in the field to participate in the decision-making process or make meaningful contributions.
To overcome the challenges of implementing MEAs in the APAC region, rare disease players can employ three key steps in addressing these challenges:
Promote conversation and cooperation across APAC countries and regulatory bodies to exchange best practises, unify standards, and establish a consistent framework for outcome-based contracting.
Pharma players should work together with hospitals and governments to develop and adopt standardised data collection, reporting, and analysis methodologies across the region to ensure consistent and reliable outcome measurements. In addition, players should leverage on existing, broader data infrastructure building initiatives to ensure embedding metrics relevant to MEAs.
Orphan drug manufacturers should work with patient groups to develop evidence-based performance metrics that accurately reflect the clinical impact of a treatment at the local level. In addition, by leveraging real-world evidence (RWE), pharma players should regularly review and update the outcomes and performance metrics to account for new evidence, therapeutic advancements, and evolving patient needs in the rare disease landscape.
Pharmaceutical companies should develop and prepare their MEA proposals with well-studied and crafted plans well ahead of HTA assessment to be relevant and actionable. Companies should contextualise the approach to the challenges of the specific market; for example, the ability of the healthcare system to collect pertinent patient-level data in routine clinical practice.
Well-implemented MEAs may serve as a tool to improve patient access to high-cost drugs while reducing payer and societal cost uncertainties, ensuring broader coverage and adherence to guidelines, improving patient outcomes, and reducing time to access. The goal is to better converge domestic policies and regulations, assist with the immediate implementation of proven best practices, and promote multisectoral cooperation and partnerships.
Alcimed is ready to support you in your endeavours related to improve access in rare diseases in the Asia Pacific region. Don’t hesitate to contact our team!
About the authors,
Alson, Project Manager in Alcimed’s Life Sciences team in Singapore
Iswan, Project Manager in Alcimed’s Life Sciences team in Singapore
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