NICE recommends novel treatment for sickle cell disease

The first sickle cell disease treatment to be approved for NHS use in the past 20 years, crizanlizumab (Adakveo) is a monoclonal antibody that acts by binding to P-selectin, a protein which is overexpressed in patients with sickle cell disease causing activation of circulating blood cells and the endothelium resulting in them becoming hyperadhesive.

The resulting blockages in the small blood vessels can cause a loss of blood flow and severe pain in episodes known as vaso-occlusive or sickle cell crises. Binding P-selectin on the surface of the activated endothelium and platelets has been shown to effectively block interactions between endothelial cells, platelets, red blood cells and leukocytes, thereby preventing vaso-occlusion.

Clinical data

The efficacy and safety of crizanlizumab were assessed in the 52-week phase II SUSTAIN study involving 198 patients with sickle cell disease and a history of vaso-occlusive crises. Patients were randomised to receive crizanlizumab 5mg/kg, crizanlizumab 2.5mg/kg or placebo, with (62.1%) or without (37.9%) hydroxycarbamide.

Treatment with crizanlizumab 5mg/kg was associated with a significant reduction in the annual rate of vaso-occlusive crises compared with placebo (45.3% reduction, p=0.010).

Crizanlizumab was associated with a low rate of adverse effects in the study, with arthralgia, nausea, back pain, pyrexia and abdominal pain the most frequently reported reactions (≥10% patients).

NICE recommendation

In line with the indications listed in the Adakveo Summary of Product Characteristics, the draft guidance from NICE recommends use of crizanlizumab for the prevention of recurrent vaso-occlusive crises in sickle cell disease patients aged 16 years and older. The drug can be given as add-on therapy to hydroxycarbamide or as monotherapy in patients for whom hydroxycarbamide is inappropriate or inadequate.

Due to uncertainty regarding the long-term effectiveness of crizanlizumab therapy and its cost-effectiveness NICE was unable to recommend the drug for routine use on the NHS at this stage. Instead the committee has recommended the treatment through a managed access agreement within the NHS, which will allow people to access the treatment while additional data to address these uncertainties are collected through clinical trials.

Conditional marketing authorisation

Adakveo has been granted conditional marketing authorisation in the interest of public health because it addresses an unmet medical need. This means that the benefit of immediate availability was deemed to outweigh the risk of less comprehensive data than normally required. New information on crizanlizumab will be reviewed at least annually by the European Medicines Agency and the Summary of Product Characteristics updated as necessary.

An entry for Adakveo will be added to MIMS when the drug is granted standard marketing authorisation.