Urgent need to define unmet medical needs in cardiovascular diseases (2024)

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In 2020, the European Commission announced a major review of the European Union’s (EU’s) pharmaceutical legislation and, in March 2023, adopted a proposal for a new Directive and a new Regulation, which will revise and replace the existing ones (Regulation 726/2004 and Directive 2001/83/EC) and the legislation on medicines for children and for rare diseases (Regulation 1901/2006 and Regulation 141/2000/EC), respectively.¹

The proposed revision builds on harmonization that has already been achieved for the authorization of medicinal products. As stated in an explanatory memorandum to the Directive of the European Parliament and the Council, ‘The overarching aim of the reform is to ensure that patients across the EU have timely and equitable access to medicines. (…) A harmonised approach at EU level also provides greater potential for incentives to support innovation and for concerted action to develop medicinal products in areas of unmet medical needs.’²

In this context, ‘unmet medical need’ (UMN) means that there is a gap or deficiency in the available medical options for preventing, diagnosing, or treating a specific health disorder, and this gap represents a need that has not been covered by current medical approaches. The concept of UMN has important implications not only for the regulatory frameworks of the European Medicines Agency (EMA) but also for European innovators, researchers, and clinicians. Regulators use it now mostly, but not exclusively, in the context of orphan medicinal products. In general terms, however, it is applicable to a wide range of situations where existing diagnostics, interventions, or therapies are incapable of adequately addressing a particular health condition or disease.

The term is all but unambiguous; indeed, a recent review yielded 16 definitions of UMN, based on various criteria.³ Regulators work on scoring and grading systems to better define what UMN really is. So far, with the adopted paradigm, the results are not particularly favourable for the cardiovascular community. Indeed, Belgium’s National Institute for Health and Disability Insurance (INAMI-RIZIV) in its 2023 edition has proposed a ranked list of UMNs. There are no cardiovascular diseases on it, despite mentioning non-orphan, non-rare conditions such as Alzheimer’s disease or treatment-resistant depression.⁴ This does not look too good for cardiologists, especially considering that Belgium wants to make UMN one of the central themes of the Belgian presidency of the Council of the EU in 2024 and that the methodology developed may be applied at the EU level.⁵

The proposed revision of the EU pharmaceutical legislation puts the concept of UMN and high UMN at the centre of its legislation, focusing on medical products for paediatric use, and orphan indications, and rewarding new drugs for patients with rare diseases who do not have any other treatment options. It is certainly not promising for cardiovascular patients. In 2022, there were no new cardiovascular drugs recommended for marketing approval among the 89 positive EMA recommendations for authorization, including 41 containing new active drugs.⁶ Analysis of the first 5 years of experience of the EMA PRIME scheme, which was set up in March 2016 to provide early and enhanced scientific and regulatory support to medicines that have the potential to significantly address patients’ UMN, revealed particularly alarming numbers. Of note, there were 384 PRIME requests received by EMA between 1 January 2016 and 30 June 2021, and out of those, only 20 were for cardiovascular diseases and just 2 (!) were granted eligibility to the PRIME scheme—which is a mere 0.5% of all submissions. For comparison, out of 111 requests for oncology drugs, 27 were granted eligibility to the PRIME scheme—which is an order of magnitude higher!⁷ At the same time, cardiovascular diseases remain the number one killer in Europe and a pressing public health challenge due to existing UMNs and inequalities in access to optimal care.⁸

From the point of view of the cardiovascular community, there is a need to work with patients, regulators, payers, and other stakeholders to identify unmet needs in cardiovascular medicine from patients’, clinicians’, and societal perspective to reverse the declining trend in cardiovascular innovation. A single definition of UMN may be challenging, and there is a clear necessity for the cardiovascular community to shift the paradigm from where it is now to where it ought to be—to include cardiovascular patients and their care at the centre of European pharmaceutical policy.

Declarations

Disclosure of Interest

P.S. reports honoraria from Novartis and Samsung. outside this work. F.Z. reports personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics,Bayer, Betagenon, Boehringer, BMS, CVRx, Cambrian, Cardior, Cereno pharmaceutical,Cellprothera, CEVA, Inventiva, KBP, Merck, NovoNordisk, Owkin, Otsuka, Roche Diagnostics,Northsea, USa2, having stock options at G3Pharmaceutical and equities at Cereno,Cardiorenal, Eshmoun Clinical research and being the founder of Cardiovascular ClinicalTrialists.T.F.L. has outside this work received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer-Ingelheim, Daichi-Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi and Vifor and until 2022 honoraria from Amgen, Dacadoo, Daichi-Sankyo, Menarini Foundation, Novartis, Novo Nordisk, an Philips. Since 2023 all honoraria from industry goes to a charity.

References

Published by Oxford University Press on behalf of the European Society of Cardiology 2024.

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