Crizanlizumab-tmca (Adakveo)

Number: 0964



Precertification of crizanlizumab (Adakveo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of crizanlizumab (Adakveo), call (866) 752-7021 (Commerical), (866) 503-0857 (Medicare) or fax (866) 267-3277.

Note: Site of Care Utilization Management Policy applies. For information on site of service for crizanlizumab (Adakveo), see Utilization Management Policy on Site of Care for Specialty Drug Infusions

Aetna considers crizanlizumab-tmca (Adakveo) medically necessary for reducing the frequency of vasoocclusive crises (VOCs) in members 16 years of age or older with sickle cell disease and prior vasoocclusive crises.

Aetna considers continued therapy with crizanlizumab-tmca (Adakveo) medically necessary when the member has experienced a reduction in the frequency of vasoocclusive crises, or has maintained such reduction, since initiating therapy with Adakveo.

Aetna considers crizanlizumab (Adakveo) experimental and investigational for all other indications.

Dosing Recommendations

Administer Adakveo 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter. 

Source: Novartis 2019.


U.S. Food and Drug Administration (FDA)-Approved Indications

  • Adakveo is indicated to reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease.

Sickle cell disease is a Mendelian recessive disorder comprised of a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent shape. Clinically, sickle cell disease is manifested most often by acute painful episodes or "crises" but with many other acute and chronic complications including a variety of serious organ system complications, life-long disabilities and even death. When red blood cells sickle, they break down prematurely, leading to hemolytic anemia. Vaso-occlusion (previously called sickle cell crisis) occur when the stiff and inflexible sickled red blood cells get stuck in small blood vessels, resulting in recurrent painful episodes (previously called sickle cell crisis) and a variety of serious organ system complications which can lead to life-long disabilities and even death. According to the Centers for Disease Control and Prevention, sickle cell disease affects approximately 100,000 Americans. The disease occurs most often in African-Americans, where 1 out of every 365 babies born have the disease. The management of acute pain in individuals with sickle cell disease (SCT) is divided into prevention of pain, treatment of acute pain episodes, and management of chronic pain. Prophylactic pain management includes reducing pain triggers such as exposure to cold temperature or respiratory triggers, dehydration, and overexertion. Hydroxyurea and L-glutamine are the two main pharmacotherapy options for reducing pain episodes. Other pain management options include non-opioid (e.g., acetaminophen and NSAIDs) and opioid treatment.

On November 15, 2019, the U.S. Food and Drug Administration approved Adakveo (crizanlizumab-tmca) for patients age 16 years and older to reduce the frequency of vaso-occlusive crisis, a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells. Crizanlizumab-tmca is the first targeted therapy approved for sickle cell disease. Crizanlizumab-tmca is a selectin blocker humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1. Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.

The crizanlizumab-tmca approval was based on the results of a randomized clinical trial enrolling 198 patients with sickle cell disease with a history of vaso-occlusive crisis (Ataga et al.; SUSTAIN Trial; NCT01895361). Ataga et al (2017) stated the up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. In this double-blind, randomized, placebo-controlled, phase 2 trial, patients were assigned to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. The authors concluded that in patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events.  

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

Other CPT codes related to the CPB:

96365 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour

HCPCS codes covered if selection criteria are met:

Crizanlizumab-tmca (Adakveo) - no specific code:

ICD-10 codes covered if selection criteria are met:

D57.00 - D57.819 Sickle-cell disorders

The above policy is based on the following references:

  1. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439.
  2. Novartis Pharmaceuticals Corporation. Adakveo (crizanlizumab-tmca) injection, for intravenous use. Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; revised November 2019.
  3. U.S. Food and Drug Administration (FDA). FDA approves first targeted therapy to treat patients with painful complication of sickle cell disease. Silver Spring, MD: FDA; November 15, 2019.