Novartis' Adakveo Rejected by NICE for Recurrent Sickle Cell Crisis Prevention in the UK

Compiled by Keke

According to recent reports by UK media, Novartis’ Adakveo (crizanlizumab) has encountered a setback in the UK healthcare market, as it failed to gain approval from the National Institute for Health and Care Excellence (NICE). Within the scope of Adakveo’s marketing authorization, NICE, the cost-effectiveness watchdog, does not recommend the drug for preventing recurrent sickle cell crises (or vaso-occlusive crises, VOCs) in patients aged 16 years or older with sickle cell disease.

Clinical evidence indicates that patients taking Adakveo experience fewer vaso-occlusive crises per year than those receiving no treatment. However, according to NICE, these findings remain uncertain due to the short duration of the trials and the limited number of participants who received the licensed dose of the medication.

Furthermore, the cost-review body also pointed out that there is uncertainty in the estimated cost-effectiveness of the drug, which may be significantly higher than the typical cost-effectiveness threshold for NHS resources. As an independent agency providing decision-making references for the drug formulary of the UK’s National Health Service (NHS), NICE holds statutory authority to determine whether drugs and medical technologies are included in the national reimbursement list.

Crizanlizumab (trade name Adakveo) is a monoclonal antibody drug developed by Novartis that targets P-selectin. P-selectin is a cell adhesion protein present on the surface of vascular endothelial cells and plays a key role in multicellular interactions that can lead to vaso-occlusion, being associated with vaso-occlusive crises in sickle cell disease. The drug limits interactions among endothelial cells, platelets, red blood cells, and white blood cells by binding to P-selectin on the surface of activated endothelial cells and platelets.

In November 2019, the drug was approved in the United States for the prevention of vaso-occlusive crises in patients with sickle cell disease. The U.S. FDA regarded crizanlizumab as a “first-in-class” drug, purportedly the first and only targeted biologic agent that works by binding to P-selectin.

In November 2020, the European Commission (EC) also approved Adakveo for the prevention of recurrent vaso-occlusive crises (VOCs) or pain crises in patients with sickle cell disease aged 16 years and older, as an add-on therapy to hydroxyurea (including HC/HU), or as monotherapy in patients for whom treatment with HC/HU is inappropriate or inadequate. The approval was based on data from the Phase 3 SUSTAIN clinical trial, which demonstrated that Adakveo significantly reduced the mean annual rate of VOCs in patients with sickle cell disease compared with placebo (1.63 vs. 2.98), corresponding to a 45% reduction.

Yet even with significant therapeutic advantages, UK regulatory and reimbursement authorities clearly place greater emphasis on balancing efficacy with long-term cost-effectiveness. Adakveo may therefore need to offer deeper discounts or other concessions to gain entry into the UK sickle cell disease market.

Reference Sources:

1. Wikipedia

2.NICE turns down Novartis' Adakveo

3.Novartis gets EC nod for Adakveo to prevent pain crises in sickle cell disease patients