Novartis has announced plans to withdraw Adakveo (crizanlizumab) from the U.S. market in 2025 [1]. The company is also voluntarily withdrawing the drug from the European Union and the United Kingdom, with withdrawal dates anticipated in 2026 [1]. This decision follows a review of the drug's overall benefit-risk profile [1].
What is Adakveo used for?
Adakveo is a medication used to treat sickle cell disease (SCD) [2]. It works by binding to P-selectin, a protein that plays a role in blood vessel inflammation and blockage, thereby reducing the frequency of vaso-occlusive crises (VOCs) [2][3]. VOCs are a hallmark of SCD and cause severe pain [3].
Why is Adakveo being withdrawn?
Novartis's decision to withdraw Adakveo stems from an assessment of its benefit-risk profile [1]. This evaluation considered new data and information that emerged after the drug's approval [1]. The company stated that this review led to the conclusion that the drug's benefits did not outweigh its risks [1].
What new data prompted the withdrawal?
While the specific new data were not detailed, the withdrawal follows recommendations from advisory committees. In November 2023, the U.S. Food and Drug Administration's (FDA) Hematologic Malignancies Advisory Committee voted overwhelmingly that the benefits of Adakveo did not outweigh its risks for treating SCD [4]. This vote was influenced by concerns regarding the drug's efficacy and a signal for potential oncologic risk, specifically a possible association with stroke [4]. An independent analysis presented at the meeting suggested a potential increased risk of stroke in patients treated with crizanlizumab [4].
What are the implications for sickle cell disease treatment?
The withdrawal of Adakveo represents a significant shift in treatment options for sickle cell disease [1]. It leaves patients and physicians with fewer therapeutic choices for managing VOCs [2]. The FDA's decision to accept the voluntary withdrawal means Adakveo will no longer be available for prescription in these major markets [1][4].
What are alternative treatments for sickle cell disease?
Current treatments for sickle cell disease include hydroxyurea, blood transfusions, and pain management [5]. Emerging therapies, such as voxelotor and L-glutamine, are also available [5]. Gene therapies are also under development and represent a potential curative approach for SCD [5].
When did Adakveo receive approval?
Adakveo received accelerated approval from the FDA in November 2019 for the treatment of SCD in patients aged 16 years and older [2][4]. It was also approved in the European Union in September 2020 [6].
What is the mechanism of action for Adakveo?
Adakveo is a humanized monoclonal antibody that targets P-selectin [3]. P-selectin is expressed on activated platelets and endothelial cells, and it plays a critical role in the adhesion of leukocytes and platelets to the vascular endothelium. By blocking P-selectin, crizanlizumab inhibits these interactions, thereby reducing the inflammatory processes and cellular adhesion that contribute to VOCs in sickle cell disease [3].
What are the risks and side effects associated with Adakveo?
Before its withdrawal, known side effects of Adakveo included infusion-related reactions, nausea, diarrhea, arthralgia, back pain, and chest pain [2][3]. As mentioned, a concern that emerged during its post-market review was a potential association with stroke, which contributed to the advisory committee's negative recommendation on its benefit-risk profile [4].
Will there be any impact on ongoing clinical trials?
The withdrawal of Adakveo from the market is a regulatory action and does not necessarily halt all ongoing research or clinical trials involving crizanlizumab. However, for trials focused on its therapeutic use in sickle cell disease, the market withdrawal may impact recruitment and the future development pathway.
Where can patients find more information?
Patients and healthcare providers seeking information about the withdrawal and alternative treatment options should consult with their healthcare providers or refer to official announcements from Novartis and regulatory agencies like the FDA [1][4].
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Sources:
[1] https://www.novartis.com/news/media-releases/novartis-announces-withdrawal-intent-adakveo-crizanlizumab-us-eu-and-uk
[2] https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-adakveo-crizanlizumab-sickle-cell-disease
[3] https://www.adakveo.com/
[4] https://www.fda.gov/advisory-committees/medical-policy-committees/hematologic-and-oncologic-drugs-advisory-committee/november-16-2023-meeting-announcement-and-webcast
[5] https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/sickle-cell-disease
[6] https://www.ema.europa.eu/en/medicines/human/EPAR/adakveo