Mieloma múltiplo: avaliação dos benefícios clínicos de medicamentos registrados no Brasil e no exterior de 2003 a 2024, e monitoramento de horizonte tecnológico.

Abstract

Multiple myeloma (MM) is a rare hematologic malignancy, and patient survival has progressively improved in recent years due to therapeutic advances. As an incurable disease and an unmet clinical need, effective regulatory decision-making and the continuous development of new therapeutic strategies are crucial to ensuring the availability of increasingly safe and effective treatments. In this context, the present study aimed to assess the clinical benefit of newly approved drugs for MM between 2003 and 2024 and to conduct a horizon scanning analysis of emerging therapies for this disease. The clinical benefit was evaluated using the European Society for Medical Oncology–Magnitude of Clinical Benefit Scale for Hematological Malignancies (ESMO-MCBS:H v1.1), considering the pivotal trials submitted to the Brazilian Health Regulatory Agency (Anvisa), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA) at the time of approval. Horizon scanning was performed based on clinical trials registered in the ClinicalTrials.gov (CTGR) and Cortellis Drug Discovery Intelligence (CDDI) databases between 2014 and 2024. A total of 17 new drugs were identified as approved by both the EMA and FDA, most of which were based on singlearm studies (64.7% and 70.6%, respectively). Accelerated approval pathways were commonly used, with 23.5% of EMA approvals and 64.7% of FDA approvals falling under expedited programs. Anvisa approved only 12 new drugs during the same period, 7 of which were granted priority review status. Biological agents accounted for the majority of approved therapies (52.9%). However, clinical benefit analysis using the ESMO-MCBS:H v1.1 scale indicated that only 4 drugs (23.5%) demonstrated a meaningful clinical benefit. Furthermore, Anivsa approvals occurred with a median delay of 11 months compared to the EMA and 19 months compared to the FDA. Shorter review times were associated with biological agents (p = 0.008), monoclonal antibodies (p = 0.035), and therapies granted Breakthrough Therapy designation (p = 0.031). The horizon scanning analysis revealed a transformation in the clinical research landscape for MM. A total of 5984 trials were screened in the CDDI database and 1936 in CTGR, resulting in 234 and 355 eligible active studies, respectively. Most trials were phase I studies (48.7% in CDDI; 50.4% in CTGR) investigating biological agents (77.4% in CDDI; 71.8% in CTGR). Cellular therapies stood out, particularly CAR-T cell products (n = 89 in CDDI; n = 110 in CTGR). A significant increase was observed in trial registrations in CTGR (APC = 1.81/year; p = 0.0189) and in the number of active trials over the last decade (APC = 18.56/year; p < 0.0001). In conclusion, the regulatory landscape was characterized by the frequent use of accelerated pathways, often based on limited clinical evidence at the time of approval. Anvisa had longer review times compared to the FDA and EMA. Nonetheless, the drugs approved in Brazil had a higher average score on the ESMO-MCBS:H v1.1 scale. Regarding access to newly approved MM therapies in the Brazilian public health system (SUS), only four therapies were evaluated by Conitec, and just two were incorporated into SUS, highlighting significant barriers to access for patients reliant on public healthcare. Meanwhile, there has been a growing prioritization of innovative biological therapies, pointing to a promising, though still challenging, future for the treatment of MM.