The Committee for Human Medicinal Products (CHMP) at the European Medicines Agency (EMA) has recommended the withdrawal of the conditional marketing authorisation issued for the monoclonal antibody Adakveo (crizanlizumab). Adakveo is used to prevent painful crises (known as vaso-occlusive crises) in patients with sickle cell anaemia aged 16 years and older. The withdrawal recommendation results from the review of the results from the STAND study, which was a prerequisite for conditional marketing authorisation. The CHMP concluded that the benefits of the medicinal product do not outweigh its risks. The European Commission followed the CHMP's recommendation on 8 August 2023.
STAND is an acronym for “Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients”. The study compared the efficacy and safety of Adakveo in individuals with a history of painful crises leading to a doctor's visit with the efficacy and safety in individuals who received a placebo after a painful crisis.
The study showed that Adakveo did not reduce the number of painful crises that led to a doctor's visit. In the first year of treatment, patients treated with Adakveo experienced an average of 2.5 painful crises leading to a doctor's visit, compared with 2.3 crises in the placebo group.
Furthermore, the average number of crises requiring a doctor's visit or treatment at home was 4.7 with Adakveo and 3.9 with placebo.
The CHMP also took data from other studies, a managed access program, and real-world data into consideration in its review. However, the studies considered had several limitations and could not definitively prove the positive effects of Adakveo or compensate for the negative results of the STAND study. One such limitation was the absence of a control group.
The STAND study did not reveal any new safety concerns, but it did show a higher rate of serious and severe treatment-related side effects for Adakveo compared to placebo.
The data available at the time of marketing authorisation had shown that Adakveo was effective in reducing the number of painful crises in patients with sickle cell anaemia. However, the data available at that time was limited and there was some uncertainty about the extent of the medicinal product's efficacy.
Adakveo received conditional marketing approval in October 2020 on the condition that the STAND study be conducted to obtain additional data. Since the results of the STAND study do not confirm the benefits previously observed with Adakveo, the CHMP concluded that the benefits do not outweigh the risks and has recommended the withdrawal of the authorisation in the EU.
The European Commission followed the CHMP's recommendation on 8 August 2023.
Updated: 30.05.2023
