January 8, 2024
The year 2023 has been remarkable in terms of regulatory developments within the UK and EU, characterised by substantial changes, innovative approvals, and strategic initiatives in the healthcare and pharmaceutical sectors. This review aims to provide a comprehensive overview of these pivotal developments, offering insights into their implications and future directions.
The Medicines and Healthcare products Regulatory Agency (MHRA) has played a key role in advancing healthcare this year. The most notable approval was the innovative treatment, Casgevy (exagamglogene autotemcel; Vertex), for sickle-cell disease and transfusion-dependent β-thalassemia. Casgevy is the first medicine to be licensed that uses the innovative gene-editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020. Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long. In the clinical trial for sickle-cell disease, 45 patients have currently received Casgevy but only 29 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these eligible patients, 28 (97%) were free of severe pain crises for at least 12 months after treatment.
In the clinical trial for transfusion-dependent β-thalassemia, 54 patients have currently received Casgevy but only 42 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these, 39 (93%) did not need a red blood cell transfusion for at least 12 months after treatment. The remaining three had more than a 70% reduction in the need for red cell transfusions1.
In addition to authorising the world-first gene therapy aimed to cure sickle-cell disease and transfusion-dependent β-thalassemia, MHRA has also played a significant part in providing patients access to many other crucial forms of treatments. Litfulo (ritlecitinib; Pfizer) for severe alopecia areata in adults and adolescents 12 years and older2; Jemperli (dostarlimab, GlaxoSmithKline) for patients with a tumour abnormality called mismatch repair deficient (dMMR) / microsatellite instability-high (MSI-H) in advanced stage cancer3; Mounjaro (tirzepatide; Eli Lilly) for weight loss and weight management in adults4; Krazati (adagrasib; Mirati Therapeutics) for a type of non-small cell lung cancer (NSCLC) with a KRAS G12C mutation5; and Tepkinly (epcoritamab; AbbVie) for diffuse large B-cell lymphoma in adults6. These approvals represent a significant step in addressing unmet medical needs and enhancing patient care, highlighting the MHRA's commitment to facilitating timely access to effective and safe treatments.
The MHRA authorised adapted COVID-19 vaccines targeting the Omicron XBB.1.5 subvariant, marking a significant advancement in the UK's pandemic response. Both Moderna's Spikevax and Pfizer/BioNTech's Comirnaty vaccines, suitable for individuals from 6 months of age, have met the MHRA's stringent standards for safety, quality, and effectiveness7,8.
In response to the evolving nature of the COVID-19 pandemic, particularly with the emergence of new variants, the UK has intensified its efforts in antiviral development and deployment. The rapid mutation of the SARS-CoV-2 virus, leading to variants with potential viral escape mechanisms, has underscored the necessity for swift action. The Antivirals and Therapeutics Taskforce, established by the UK's Department of Health and Social Care, held a workshop on 12 September 2022, involving expert pharmacologists, the UKHSA, and the MHRA. This initiative aimed to address knowledge gaps and enhance the evaluation of antiviral drugs and monoclonal antibodies. This comprehensive approach signifies the UK's proactive stance in managing the pandemic and adapting to its challenges9.
European Commission (EC) has granted conditional marketing authorisation for Tepkinly (epcoritamab; AbbVie) as a standalone treatment for adult patients facing relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after undergoing two or more lines of systemic therapy. This marks a significant milestone as Tepkinly becomes the first and only subcutaneous bispecific antibody to receive approval for treating this patient group within the European Union (EU) and in Liechtenstein, Norway, and Iceland.
The benefits of Tepkinly were evaluated in a study involving 157 adults with DLBCL or a related lymphoma whose cancer had returned or was not responding after at least two other treatments. In this study, Tepkinly was given for an average of four months and was not compared with other medicines or placebo. Of the patients with DLBCL, 62% (86 out of 139) had either a complete response (no sign of cancer) or a partial response to Tepkinly; they maintained these responses for an average of around 16 months.
Crucially, the safety profile of Tepkinly across the entire LBCL patient cohort (which included DLBCL patients, totalling 167) was manageable10.
Alongside the MHRA, the EMA has also played a key role in advancing healthcare this year. There have been 23 new (non-orphan) medicinal approvals, 22 orphan medicine approvals, 8 biosimilar products and 16 Generic/ Hybrids/ Informed Consent. Notable approvals include Jaypirca (pirtobrutinib; Eli Lilly) for relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor11; Apretude (cabotegravir; ViiV Healthcare) for Pre-exposure prophylaxis of HIV-1 infection12; Enrylaze (crisantaspase; Jazz Pharmaceuticals) for adults and children aged one month and older to treat acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL)13; Orserdu (elacestrant; Stemline Therpaeutics) for the treatment of postmenopausal women, and men, with estrogen receptor (ER) positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor14. These approvals represent a significant step in addressing unmet medical needs and enhancing patient care, highlighting the EMA’s commitment to facilitating timely access to effective and safe treatments.
The EU has seen a wave of regulatory transformations this year. The adoption of electronic Patient Information (ePI) for selected medicines marks a digital shift in patient communication, aiming to improve accessibility and understanding of medicinal information15.
The EMA has also published guidance for industry to mitigate medicine shortages. The guidance describes the various stakeholders involved in the medicine supply chain and their responsibilities and role in the prevention and management of medicine shortages. It provides ten recommendations for marketing authorisation holders, wholesalers, distributors and manufacturers to minimise the occurrence of medicine shortages and their impact16. This is alongside the significant reforms in pharmaceutical legislation. These developments reflect the EU's commitment to ensuring the availability, safety, and efficacy of medicines across member states.
The revised transparency rules for the EU CTIS in 2023 brought significant changes to the handling of clinical trial data and documents. A notable amendment is the removal of the deferral mechanism, which previously allowed sponsors to postpone the publication of specific data for up to seven years to protect personal data and commercially confidential information (CCI).
These updated rules achieve a balance between ensuring transparency and safeguarding CCI. They are advantageous for patients by ensuring early publication of key clinical trial information deemed crucial by them. For sponsors, the rules simplify processes related to the protection of CCI and personal data. Healthcare professionals also benefit from a more user-friendly system, which improves access to clinical trial information and enhances awareness of potential treatment options. Overall, these revisions represent a pivotal development in EU clinical trial regulation, prioritising transparency while maintaining necessary protections17.
The European Commission's recent proposal to overhaul EU pharmaceutical legislation marks a substantial advancement. This proposal aims to update both the general pharmaceutical laws (Regulation 726/2004 and Directive 2001/83/EC) and specific regulations for paediatric and rare disease medicines (Regulation 1901/2006 and Regulation 141/2000/EC).
Key objectives of this revision include ensuring equitable access to safe, effective, and affordable medicines for all EU patients, reinforcing the supply chain to guarantee medicine availability across the EU, and promoting an innovative environment for medicine research and production in Europe. Moreover, the proposal places a strong emphasis on environmental sustainability within the pharmaceutical sector and tackles critical health concerns such as antimicrobial resistance (AMR) through a holistic One Health approach18.
Thus, manufacturers will have to review their research, development, and marketing strategies to meet these eligibility criteria for the extension of the duration of protection.
In summary, this legislative update represents a significant stride towards a more cohesive, environmentally conscious, and patient-focused pharmaceutical system in the EU, aligning with modern health imperatives and the drive for innovation.
The year 2023 has been pivotal in embracing technological advancements in healthcare. The increasing use of artificial intelligence (AI) in medicine and the integration of real-world evidence in regulatory decision-making have been notable trends. These innovations are not only enhancing drug development and patient care but also paving the way for more personalised and efficient healthcare solutions. The EMA has published a draft reflection paper outlining the current thinking on the use of AI to support the safe and effective development, regulation and use of human medicines19. The paper highlights the need for a risk-based approach in AI/machine learning tool development and deployment, ensuring data integrity and compliance with regulatory standards. It emphasises the importance of data protection, ethical considerations, and the implementation of AI in a manner that respects fundamental rights and promotes trustworthiness.
Special attention has been given to paediatric medicine development, with initiatives aimed at fostering research and approval of paediatric treatments. A major outcome of this work is the launch of a pilot phase for a ‘stepwise PIP’ agreement: under this framework, it will be possible in certain cases to agree on a partial development programme, conditional on the development of a full PIP once evidence becomes available over time. This will allow more flexibility as the agency will agree PIPs for innovative medicines where crucial information needed to define certain parts of the plan is not yet available, while planning the conditions and milestones for companies to return to EMA’s paediatric committee (PDCO) and discuss the uncertainties once more data are available20. Currently the agency is assessing the pilot project, and we look forward to seeing how this will progress.
The EMA, the EC and the Heads of Medicines Agencies (HMA) are gradually phasing out of COVID-19 regulatory flexibilities which signals a transition towards a post-pandemic regulatory environment. These changes underscore the importance of adapting regulatory frameworks to meet evolving healthcare challenges21.
The developments in the UK and EU regulatory landscape in 2023 have laid a foundation for future advancements in healthcare. These changes not only address current needs but also demonstrate a proactive approach towards embracing innovation and improving patient outcomes. As we look forward, these regulatory developments will undoubtedly continue to shape the future of healthcare and pharmaceutical industries.
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