CrizanlizumabEdit
Crizanlizumab is a humanized monoclonal antibody that targets P-selectin, a cell-adhesion molecule implicated in the sickle cell disease (SCD) pathophysiology. By binding P-selectin, crizanlizumab aims to interrupt the sticky interactions among activated endothelium, platelets, leukocytes, and sickled red blood cells that can lead to vaso-occlusive crises (VOC). It is marketed under the brand name Adakveo by Novartis and is approved for reducing the frequency of VOC in patients aged 16 years and older with sickle cell disease who experience such crises. Crizanlizumab is administered as an intravenous infusion every four weeks.
Mechanism of action
Crizanlizumab binds to P-selectin, preventing its interaction with PSGL-1 (P-selectin glycoprotein ligand-1) on leukocytes and other circulating cells. This reduces the tethering and rolling of cells to the vascular endothelium, a key step in the formation of occlusive events that underlie VOC. By limiting these adhesion events, crizanlizumab seeks to lower the probability of VOC episodes and the associated pain and hospital utilization that often accompany SCD. For context, the target and related pathways are discussed in entries on P-selectin and vaso-occlusive crisis.
Medical uses
Crizanlizumab is indicated to reduce the frequency of VOC in patients with sickle cell disease aged 16 years and older. It is not a cure for SCD, nor is it a substitute for disease-modifying therapies when those therapies are clinically appropriate. In practice, crizanlizumab is used as part of a broader treatment plan that may include hydroxyurea or other disease-modifying approaches, depending on the individual patient’s history and risk profile. The therapy can be used in patients who are already receiving other standard treatments, reflecting a market-driven emphasis on targeted adjunctive options.
Clinical evidence
The pivotal clinical data come from a randomized, placebo-controlled trial known as the SUSTAIN study. In this trial, crizanlizumab at a higher dose significantly reduced the annual rate of VOC leading to healthcare visits compared with placebo, with patients experiencing a meaningful reduction in crisis events. The 5 mg/kg dose was associated with the most substantial benefit in reducing VOC frequency, contributing to regulatory approval and labeling that supports its use in the specified patient population. Additional follow-up and real-world studies have sought to clarify the durability of benefit, the consistency of effect across diverse patient groups, and how crizanlizumab fits with other sickle cell therapies. Related discussions can be found under entries for SUSTAIN trial and vaso-occlusive crisis.
Safety and adverse effects
As with other monoclonal antibody therapies, crizanlizumab can cause infusion-related reactions and infections, among other potential adverse effects. Commonly reported events in trials and post-marketing experience include headaches, fever, abdominal or back pain, nausea, and infusion reactions. Serious adverse effects require clinical attention and may necessitate interruption or discontinuation of therapy. The safety profile is weighed against the benefit of reducing VOC frequency, particularly in patients with frequent crises.
Dosing and administration
Crizanlizumab is given as an intravenous infusion, typically every four weeks. The dosing and administration are managed by clinicians experienced in treating SCD and tailored to the patient’s weight and clinical status. Infusion times and monitoring for adverse reactions are standard parts of the treatment protocol.
Regulatory status and history
Crizanlizumab received regulatory approval in the United States for reduction of VOC frequency in patients aged 16 years and older with sickle cell disease who experience VOC. It is marketed as Adakveo by Novartis in several markets. The development history traces back to the earlier work of Selexys Pharmaceuticals before the asset was acquired by Novartis, with clinical trials establishing the benefit in high-need VOC reduction. The drug’s regulatory narrative sits alongside other targeted therapies for SCD, such as hydroxyurea and newer gene-based approaches in development.
Pricing, access, and policy debates
Crizanlizumab represents a high-cost, targeted therapy aimed at a relatively narrow patient subset—those with frequent VOC despite standard care. In discussions about healthcare spending, proponents emphasize that reducing VOC can lower hospitalizations, emergency visits, and pain burden, potentially offsetting drug costs over time. Critics raise concerns about price, payer access, and whether the magnitude of benefit justifies the expense for all eligible patients. The debate often centers on value-based pricing, patient selection, and the role of payer systems in ensuring access while preserving incentives for pharmaceutical innovation. Supporters argue for enabling patient choice and market-based negotiation, while opponents warn against overreliance on expensive specialty therapies without clear population-wide impact. These debates are reflected in broader conversations about drug pricing and healthcare access for rare or high-need conditions.