Brand Name
Adakveo
Generic Name
Crizanlizumab
View Brand Information FDA approval date: April 21, 2017
Classification: Selectin Blocker
Form: Injection
What is Adakveo (Crizanlizumab)?
ADAKVEO ® is indicated to reduce the frequency of vaso-occlusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease. ADAKVEO is a selectin blocker indicated to reduce the frequency of vasoocclusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease.
Approved To Treat
Top Global Experts
Save this treatment for later
Not sure about your diagnosis?
Tired of the same old research?
Related Clinical Trials
A Phase III, Multicenter, Randomized, Placebo Controlled, Double-blind Study to Assess Efficacy and Safety of Crizanlizumab (5 mg/kg) Versus Placebo, With or Without Hydroxyurea/Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Frequent Vaso-Occlusive Crises
Summary: A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.
An Open-label, Multi-center, Phase IV, Rollover Study for Patients With Sickle Cell Disease Who Have Completed a Prior Novartis-Sponsored Crizanlizumab Study
Summary: This is a multi-center multi-national rollover study to allow continued access to crizanlizumab for patients with sickle cell disease (SCD) who are on crizanlizumab treatment in a Novartis-sponsored study (parent study) and are benefiting from the treatment as judged by the investigator.
An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
Summary: A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB. Subjects will be screened for up to 28 day...
Related Latest Advances
Brand Information
ADAKVEO (crizanlizumab)
1INDICATIONS AND USAGE
ADAKVEO
2DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/10 mL (10 mg/mL) as a clear to opalescent, colorless to slightly brownish-yellow solution in a single-dose vial.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Infusion-related reactions
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Sickle Cell Disease
SUSTAIN Trial
The safety of ADAKVEO was evaluated in the SUSTAIN trial
Among the 66 patients that received the recommended dose (5 mg/kg), 83% were exposed for 6 months or longer and 61% were exposed for approximately one year; forty-two (64%) patients were treated with ADAKVEO in combination with hydroxyurea.
Serious adverse reactions were reported in 2 patients (3%) treated with ADAKVEO 5 mg/kg; both reactions were pyrexia.
Two deaths (3%) occurred in the ADAKVEO 5 mg/kg treatment group. None of the deaths were considered to be related to ADAKVEO.
The most common adverse reactions (≥ 10%) were arthralgia, nausea, back pain, abdominal pain, pyrexia, and diarrhea.
Table 1 summarizes the adverse reactions in the SUSTAIN trial.
Clinically relevant adverse reactions (all Grades) that were reported in less than 10% of patients treated with ADAKVEO included: oropharyngeal pain, vomiting, pruritus (pruritus and vulvovaginal pruritus), musculoskeletal chest pain, myalgia, infusion-site reaction (infusion-site extravasation, infusion-site pain, and infusion-site swelling), and infusion-related reaction.
STAND Trial
The safety of ADAKVEO was also evaluated in the STAND trial
Among the 84 patients that received the recommended dose (5 mg/kg), 93% were exposed for approximately 6 months or longer and 88% were exposed for approximately one year; sixty-two (74%) patients were treated with ADAKVEO in combination with hydroxyurea.
Serious adverse reactions were reported in 2 patients (2%) treated with ADAKVEO 5 mg/kg and this reaction was pain. The most common adverse reactions (≥ 10%) were headache, nausea, fatigue, vomiting, and oropharyngeal pain.
Clinically relevant adverse reactions (all Grades) that were reported in less than 10% of patients treated with ADAKVEO or events having a difference of less than 3% between ADAKVEO treatment arms and placebo included: diarrhea, pruritus, dizziness, infusion-related reaction, infusion-site reaction.
5DESCRIPTION
Crizanlizumab-tmca is a P-selectin blocker humanized IgG2 kappa monoclonal antibody that binds to P-selectin. Crizanlizumab-tmca is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is composed of 2 heavy chains, each containing 448 amino acids, and 2 light chains each containing 218 amino acids, with a theoretical molecular weight of approximately 146 kDa.
ADAKVEO (crizanlizumab-tmca) injection is supplied as a sterile, preservative-free, clear to opalescent, colorless to slightly brownish-yellow solution for dilution and subsequent administration by intravenous infusion. Each 10 mL vial contains 100 mg crizanlizumab-tmca, citric acid (5.4 mg), polysorbate 80 (2 mg), sodium citrate (50.5 mg), sucrose (753.3 mg), and water for injection with a pH of 6.
6CLINICAL STUDIES
SUSTAIN
The efficacy of ADAKVEO was evaluated in patients with sickle cell disease in SUSTAIN [NCT01895361], a 52-week, randomized, multicenter, placebo-controlled, double-blind study. A total of 198 patients with sickle cell disease, any genotype (HbSS, HbSC, HbS/beta
Patients received ADAKVEO (with or without hydroxyurea) and were allowed to receive occasional transfusions and pain medications [i.e., acetaminophen, NSAIDs, and opioids] on an as needed basis.
Patients recruited in the study had complications associated with sickle cell disease and other comorbidities, including a history of acute chest syndrome (18%); pulmonary hypertension (8%); priapism (7%); psychiatric manifestations (25%), including depression and anxiety; hypertension (17%); cholelithiasis (17%). Demographic and other baseline characteristics were similar among the treatment groups (see Table 3).
Efficacy was evaluated in the SUSTAIN study by the annual rate of VOCs leading to a healthcare visit. A VOC leading to a healthcare visit was defined as an acute episode of pain with no cause other than a vasoocclusive event that required a medical facility visit and treatment with oral or parenteral opioids, or parenteral NSAIDs. Acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism (requiring a visit to a medical facility) were also considered VOCs.
Patients with sickle cell disease who received ADAKVEO 5 mg/kg had a lower median annual rate of VOC compared to patients who received placebo (1.63 vs. 2.98) which was statistically significant (p = 0.010). Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or hydroxyurea use.
Thirty-six percent (36%) of patients treated with ADAKVEO 5 mg/kg did not experience a VOC compared to 17% of placebo-treated patients. The median time to first VOC from randomization was 4.1 months in the ADAKVEO 5 mg/kg arm compared to 1.4 months in the placebo.
The main efficacy results of the pivotal study, SUSTAIN, are summarized in Table 4.
STAND
The efficacy of two doses of ADAKVEO, with or without HU/HC, was evaluated, but not established, in the STAND trial [NCT03814746], a randomized, placebo-controlled, double-blind, multicenter clinical study in adolescent and adult sickle cell disease patients with a history of VOCs. The efficacy results of STAND study are summarized in Table 6 below.
In this study, VOC was defined as a pain crisis (acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID. Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration were considered VOCs in this study.
A total of 252 sickle cell disease patients were randomized to the study, 85 in placebo arm, 84 in ADAKVEO 5 mg/kg arm and 83 in ADAKVEO 7.5 mg/kg arm. The 7.5 mg/kg ADAKVEO dose is not approved and is not recommended for use. Demographic and other baseline characteristics were similar among the treatment groups (see Table 5).
The percentages for subgroups of race and genotype do not add up to 100% due to rounding to 1 decimal place. The results of the efficacy analysis did not confirm the statistical superiority of ADAKVEO over placebo in reducing VOCs leading to a healthcare visit over the first-year post randomization.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
ADAKVEO (crizanlizumab-tmca) injection is a sterile, clear to opalescent, colorless to slightly brownish-yellow solution for intravenous infusion supplied as:
Carton containing one 100 mg/10 mL (10 mg/mL) single-dose vial NDC 0078-0883-61
The single-dose vial has a rubber stopper and an aluminum cap with a plastic flip-off disk. Each 10 mL vial is made of Type 1 glass.
Storage and Handling
- Store and transport refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
- Do not shake. Do not freeze.
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Infusion-Related Reactions
Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions
Interference With Automated Platelet Counts
Advise patients to inform their healthcare provider that they are receiving ADAKVEO prior to any blood tests due to the potential interference with laboratory tests used to measure platelet counts
Manufactured by:
US License No. 1244
© Novartis
T2024-48
9PRINCIPAL DISPLAY PANEL
NDC 0078-0883-61
Rx Only
ADAKVEO
(crizanlizumab-tmca)
100 mg/10 mL
For intravenous infusion after dilution.
1 Single-Dose Vial.
NOVARTIS
