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Refrigerated Storage

AdakveoNovartis Pharmaceuticals

Novartis Pharmaceuticals
Adakveo
10 mg/ml concentrate for solution for infusion

Contact Novartis in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

29 October 2021
London MI Service

New Medicines

AdakveoPrevention of vaso-occlusive crises (VOC) in sickle cell disease in patients aged 16 years and older

Information

Adakveo
New molecular entity
Novartis
Novartis

Development and Regulatory status

Launched
Approved (Licensed)
Launched
October 2021
Yes
Yes
Oct 21NHS England agrees a deal with Novartis to make crizanlizumab available in the UK. NHS list price is £1,038 per 100mg/10mL vial. NICE guidance is due in November [18,19].
Jun 21MHRA added Adakveo to the Orphan Register list, and in Jan 21, it approved Adakveo for prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older. It can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. [17].
Oct 20Approved in EU [16].
Aug 20Has been available in the US since at least Dec 19 [15].
Jul 20Recommended for EU conditional approval by CHMP - the full indication is "for the prevention of recurrent vaso occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older. It can be given as an add on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate." It should be prescribed by physicians experienced in the management of sickle cell disease [14]. Conditional approval indicates that the information available is less than would usually be required, but that the medicine fulfils a significant unmet need and the benefit to risk balance is considered to be acceptable under those circumstances; the manufacturer will normally be expected to provide further clinical data to retain the marketing authorisation.
Nov 19Approved in the US [12]
Jul 19Filed in EU via centralised procedure [11].
Jul 19FDA accept BLA for Priority Review [10].
Jan 19Granted breakthrough therapy designation in the US for the prevention of vaso-occlusive crises (VOCs) in patients of all genotypes with sickle cell disease (SCD) [9].
Oct 18FDA filing anticipated in 2019 [8].
Mar 18Filings now planned for 2019 [7].
Jul 17Filings now expected 2018 [5].
Mar 17Filing planned 2020 [4].

Category

Anti-P-selectin monoclonal antibody that binds P-selectin on endothelial cells and platelets in blood vessels preventing vaso-occlusion
Painful crises in sickle cell disease are caused by vaso-occulsion resulting in ischaemic pain, including joint pain, tachypnoea, abdominal pain, renal colic, stroke and other consequences. Over 90% of hospital admissions in sickle cell disease are related to painful crises [2].
Prevention of vaso-occlusive crises (VOC) in sickle cell disease in patients aged 16 years and older
Intravenous

Further information

Yes

Trial or other data

Dec 19Further secondary endpoint data from the PII SUSTAIN trial reported at the American Society of Hematology annual meeting show that the drug could reduce the number of hospitalisations by 40% [13].
Oct 18Post hoc analysis of SUSTAIN trial found more patients treated with crizanlizumab did not experience a vaso-occlusive crisis (VOC) vs those treated with placebo (35.8% vs 16.9%), specifically patients with a history of 2-10 VOCs in the previous year. FDA filing anticipated in 2019 [8].
Dec 16Results of NCT01895361 published in NEJM. Crizalizumab (CZ) therapy (at 5mg/kg, n=67) had a lower rate of SCPC vs placebo (n=65) over 52 weeks (1.63 vs 2.98, p=0.01). The median time to first crisis was longer for CZ (4.07 vs 1.38 months, p=0.001). Rate of SCPC per year for the 2.5mg/kg dose was 2.01, which was not statistically different to rate with placebo [3].
Dec 16PII study (NCT01895361, SUSTAIN) in 198 patients found that crizanlizumab, (formerly SelG1), an anti-P-selectin antibody, reduced the median annual rate of sickle cell-related pain crises (SCPC) by 45.3% compared to placebo (1.63 vs 2.98, p=0.010) in patients with or without hydroxyurea therapy[1].

Evidence based evaluations

AdakveoSickle cell disease - prevention of vaso-occlusive crises (VOC) in patients aged 12 to 15 years

Information

Adakveo
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Anti-P-selectin monoclonal antibody that binds P-selectin on endothelial cells and platelets in blood vessels preventing vaso-occlusion
SCD is thought to be the most common severe genetic disease in the UK and France, with 10,000-15,000 people affected. The prevalence of SCD is highest in sub-Saharan Africa. The sickle beta globin gene is spread widely throughout Africa, the Middle East, the Mediterranean and India (eg, sickle genes are present in 1 in every 50 Asians and 1 in every 100 Northern Greeks). The gene has spread through population movement to the Caribbean, North America and Northern Europe [1].
Sickle cell disease - prevention of vaso-occlusive crises (VOC) in patients aged 12 to 15 years
Intravenous