Cancer is a disease characterized by the uncontrolled growth of transformed cells that evolve through natural selection (Brown et al., 2023). According to the World Health Organization (WHO), approximately 1 in 6 deaths is caused by cancer. It is the second leading cause of death globally, with its burden continuing to grow and placing substantial physical, emotional, and financial strain on individuals, families, communities, and healthcare systems (WHO, 2025). Up to date, companies seeking marketing approval for medicines focused to treatment of cancer in the European Union (EU) and in the European Economic Area (EEA) must submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) through the Centralized Procedure (CP). The CP is ruled by regulation European Commission (EC) 726/2004, which is coordinated by the EMA followed by authorization granted by the EC (European Commission, 2019).

In medicine development, patients with serious diseases and unmet medical needs often face long waits, as both investigative therapy development and health authority review processes can feel unreasonably slow (Vallano et al., 2023). In light of this, the EMA has established special status and expedited programs to encourage and/or to accelerate both drug development and the review of MAAs for promising therapies targeting serious diseases and unmet medical needs. These include orphan designation (OD), priority medicines (PRIME), conditional marketing authorizations (CMA) (or exceptional circumstances–EXC), and accelerated assessment (AA). OD supports the development of treatments for rare diseases through regulatory and financial incentives (Fermaglich and Miller, 2023). The PRIME program facilitates the development of treatments for unmet medical needs by allowing early and active interaction with regulatory authorities (Alaburde et al., 2025). CMA and EXC seek to accelerate patient access to treatments for unmet medical needs by moving certain stages of the drug development process to after approval; however, EXC is approached when comprehensive data are not available (Maksimova et al., 2024). MAAs under AA program have the procedural time reduced through a faster, but no less rigorous, evaluation (Del Grosso et al., 2025). In addition, the availability of a guidance, known as scientific advice (SA) or as protocol assistance (in case of MAA under OD), throughout the development and submission phases helps facilitate and streamline the process (EMA, 2025a).

Previous studies have analyzed medicines applications in the EU over specific periods (Regnstrom et al., 2010; Grössmann et al., 2021; Costa Gonçalves et al., 2022; Ruuskanen et al., 2024). However, there is a lack of recent, comprehensive, and systematic studies evaluating the characteristics of MAA procedures of new medicines for cancer therapy, particularly regarding the impact of SA, OD and expedited programs on the procedural time. Therefore, the present study aims to identify trends in oncology MAAs over the past 5 years, highlighting procedural time, SA, OD and expedited programs, taking into account company sizes and product categories.

The present method was performed according to Garsen et al. (2021), with some modifications. In addition, Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines have been followed (Moher et al., 2009).

Over the past decade, drug discovery has advanced through the evolution of preclinical and clinical research, playing a pivotal role in translating biological insights into oncology therapeutic strategies (Al-Karmalawy et al., 2025). In view of this, the present study summarizes the key features of EU applications for new cancer therapy drugs over 5 years, focusing on regulatory insights, time-frame relevance, and evidence-based conclusions related to a critical health issue.

A previous study showed an average of 9.6 oncology applications per year in the EU during the period from 2010 to 2019 (Garsen et al., 2021). Here, it was possible to confirm a rise of 12.5% in the total number of MAAs in the last 5 years, with an average of 12 per year. The inclusion of regulatory programs and incentives aimed at accelerating procedural timelines can be considered a potentially attractive tool for pharmaceutical companies, which may, in turn, stimulate anti-cancer research. Furthermore, compared with the 2010–2019 period, the number of oncology MAAs receiving a positive CHMP opinion has increased markedly, from 89% to 98% in the present analysis. Conversely, the proportion of negative opinions decreased from 11% to 2%. This improvement may be associated with the increase of the quality and reliability of clinical development plans and scientific guidance by the use in SA, which rose from 81% to 92%. The primary purpose of SA is to assist medicine developers in generating sound and reliable evidence on a product’s efficacy and safety (Tavridou et al., 2020).

Drug discovery and development can take up to 10 years and might require large investments before reaching the patient (Berdigaliyev and Aljofan, 2020). Although small companies, together with academia, represent the main sources of oncology drug discovery, large-sized companies predominantly hold responsibility for the clinical development and process approval of these drugs (Kennedy et al., 2023). Similarly to Garsen et al. (2021), the data shown in this study revealed a relatively high proportion of 72% of large-sized companies as MAA holders. The correlation between large-sized company holders and positive application results implies that having ample resources and regulatory experience plays yet a crucial role in achieving marketing authorization approval (Regnstrom et al., 2010).

Among the therapeutic indications in oncology, the present study shows a rise of indications pertaining to blood cancers (from 32% to 54%), lung cancers (from 14% to 17%), and ovarian and peritoneal cancers (from 3% to 5%), respectively, when compared with the period of 2010–2019 reported in the literature (Garsen et al., 2021). On the other side, some cancer indications have decreased in relation to the previously mentioned period, such as skin cancers (from 15% to 5%), gastrointestinal and colorectal cancers (from 7% to 6%), prostate cancers (from 7% to 2%), and renal cancers (from 4% to 0%), respectively. Several types of cancers have low prevalence, and are therefore considered rare diseases. As a support for the development of treatments for rare diseases, OD drugs receive regulatory and financial incentives (Fermaglich and Miller, 2023). Although OD is supported by promising non-clinical and/or early clinical data, the efficacy and safety of these products remain to be established, and the later stages of development are often the most challenging (Mulder et al., 2021). The present study revealed that the most of the oncology MAAs (60%) applied to the marketing authorization with an OD status during the period analyzed. However, only 40% of the total of MAAs remained under OD at the moment of the CHMP opinion. This result is similar to what has been reported in the literature (Garsen et al., 2021). Concerning this, OD is typically removed when the marketing authorization holder requests it, often after the drug is approved and effective alternative therapies are available. In general, the OD withdrawal likely reflects a strategic regulatory decision due to market evolution together with insufficient clinical data to demonstrate a significant benefit over existing treatments, which were already available for the same therapeutic indications (Montanaro et al., 2021). According to Gomez-Ferreria et al. (2025), providing the EMA with additional resources and responsibilities could help retain existing developers of orphan medicines and attract new ones to the field. This, in turn, would likely boost clinical trial activity, facilitate market approvals, and improve the availability of orphan medicines throughout Member States.

Expedited programs, such as PRIME, CMA (or under EXC), and AA programs benefit MAAs by providing early regulatory guidance, accelerating development, enabling approval based on preliminary data, or shortening procedural timelines. In the present study, a rise was observed in the number of MAAs under PRIME (from 3% to 10%), CMA (from 24% to 42%), and AA (from 34% to 37%) programs when compared with literature data that analyzed the period from 2010 to 2019 (Garsen et al., 2021). Still relative to the previous period, a reduction (from 86% to 57%) was observed in the number of MAAs under AA that reverted to the standard procedural time. Furthermore, the proportion of MAAs with no expedited program (i.e., AA, CMA, and PRIME) exhibited a slight reduction (from 40% to 37%). All this together, likely reflecting improved dossier quality and more proactive engagement with the CHMP, which allowed applications to remain within the accelerated review timeline. In this regard, the experience factor, reflected by the predominance of large-sized companies as MAA holders, as well as the majority of MAA holders who have obtained SA, could be considered a decisive element related to the acquisition and maintenance of these programs by the end of the procedure.

Within the CP, the EMA aims to complete the evaluation of both original submissions in 210 active review days. This timeline excludes the periods when the review time is suspended to allow the applicant to address EMA inquiries, which often extends the total procedural time of the assessment process (EMA, 2025a). In the present study, the analysis of procedural time revealed that the size of the holding company, participation in the AA program, and SA might be considered factors influencing the reduction of total procedural time. However, only the AA program is directly related to a formal EMA time reduction, while SA only implies the general quality of the dossiers and applicant’s responses associated with CHMP questions, which, in turn, affects the clockstop time. Another component observed that affects the total procedural time is the time to answer the LoQ (as known as first clockstop). Similarly with Garsen et al. (2021), the present study shows that the majority of the MAAs under standard procedural time were able to address EMA inquiries within the required 3-month time-frame. Nonetheless, the proportion of MAAs with small molecules involved exhibited an increase during the period of 2010–2019 (from 69%), in relation to the period of 2020–2024 (to 90%), while the MAAs with biotechnological products involved showed a slight reduction (from 69% to 60%). The fact that large-sized companies formed the majority of the applications in the last 5 years may have contributed to this outcome. Likewise, the high number of SA meetings during drug development and the procedure assessment, might have contributed to higher dossiers quality in the last years.

In summary, the present study highlights the key features of oncology applications in the EU in the last 5 years. Moreover, despite the low number of MAAs under OD and expedited programs, especially in AA program, their importance in the quality of oncology products and in shortening patient access to these therapies is notable. In addition, SA has been shown as a helpful guidance tool during all the process, which might be contributed to reduce both the time of response to LoQ and the procedural time. However, this study has certain limitations, including the small number of MAAs with specific characteristics, what hindered suitable comparisons, and the reliance on publicly available data, which may not fully reflect unpublished regulatory interactions.

The number of oncology MAAs has increased over recent years, particularly for mAbs and blood cancer indications. The ongoing growth of oncology MAAs, particularly for biotechnology-related products, emphasizes a continued need for streamlined regulatory pathways that balance efficiency with rigorous assessment, ultimately facilitating faster patient access to innovative therapies, especially for rare diseases. The fact that large pharmaceutical companies represented the majority of applicants in the EU, together with SA, may be associated with shorter procedural times, highlighting the value of experience and guidance in expediting regulatory evaluations. These findings underscore the importance of early and structured regulatory engagement, particularly for medium- and small-sized companies, to optimize submission strategies and reduce delays.