Note: REQUIRES PRECERTIFICATION Precertification of crizanlizumab (Adakveo) is required of all Aetna participating providers and members in applicable plan designs. She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies. The CHMP opinion was based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of … Laboratory Test Interference: Platelet Counts. We are sorry that this post was not useful for you! You’ll have access to the site in a moment, or click continue to close this message and advance directly to the site. The CHMP opinion was based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo (P=.010), equivalent to a 45% reduction. Member is not concurrently enrolled in a clinical trial to receive an experimental therapy for SCD e. Dose does not exceed the following: i. Am J Hematol. IMPORTANT SAFETY INFORMATION AND INDICATION. Sickle cellrelated pain crises are the primary cause of health care encounters in patients with sickle cell disease.1 These crises result in a decrease in quality of life2 and an increase in the risk of death.3 Crises are th… Findings from SUSTAIN demonstrated that Adakveo significantly reduced the frequency of annual VOCs by 45% compared to placebo (1.63 versus 2.98) at the 5 mg/kg dose. Ataga KI, Kutlar A, Kanter J, et al. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage - Administer ADAKVEO 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter. } No votes so far! The trial showed that Adakveo lowered the median annual rate of VOCs to 1.63 compared to 2.98 for the placebo group, a reduction of 45%. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. The study’s main goal was to evaluate the impact of treatment on the frequency of annual VOCs requiring a visit to a medical facility and treatment with either opioids or nonsteroidal anti-inflammatory drugs (NSAIDs) to control pain. It does not provide medical advice, diagnosis or treatment. Now you can find the tools you need to help manage your patients, all in one place! Table 1summarizes the adverse reactionsin the SUSTAIN trial. If ADAKVEO is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule. .uso-brand-details h3.brandColor { Novartis Pharmaceuticals Corp; November 2019. text-transform: none !important; The most common side effects of treatment included joint pain (18%), nausea (18%), back pain (15%), and fever (11%). Watch Ifeyinwa (Ify) Osunkwo, MD, MPH, discuss the clinical results of ADAKVEO treatment. Data on file. The range of days hospitalized for the ADAKVEO and placebo population was 0 to 131 days and 0 to 307 days, respectively.3, ADAKVEO achieved a clinically meaningful reduction in the median annual rate of days hospitalized1,2. ADAKVEO (Crizanlizumab-tmca) 12 Version date: April 2, 2018 1 Executive Summary Product Introduction Crizanlizumab-tmca (ADAKVEO®, SEG101) is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1. Advise pregnant women of the potential risk to a fetus. font-size: 11px !important; Results are based on 2 post hoc analyses of the key secondary end point and are observational in nature; as such, they were not powered to show statistical significance. 46% of patients treated with ADAKVEO were not hospitalized during the trial vs 35% with placebo (31 of 67 patients vs 23 of 65 patients), Median time to first hospitalization of 6.3 months with ADAKVEO vs 3.2 months with placebo, 22% of patients who completed the 12-month treatment period did not experience a VOC with ADAKVEO vs 8% with placebo (15 of 67 patients vs 5 of 65 patients; OR=3.57; 95% CI: 1.20, 10.63). The approval follows a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) in July based on results of the SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared with placebo (P=.010), equivalent to a 45% reduction. Date: 05 Dec 2019. font-size: 24px !important; East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). Novartis Pharmaceuticals Corp; July 2013. 6. “Vaso-occlusive crisis can be extremely painful and is a frequent reason for emergency department visits and hospitalization for patients with sickle cell disease,” Pazdur added. Administer ADAKVEO 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter. Full prescribing information for Adakveo, including recommended dosing schedules and safety warnings, can be found here. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns. “We are pleased to help reimagine medicine together with the sickle cell community and offer new hope for fewer VOCs.”. The FDA’s decision to approve Adakveo 5 mg/kg is based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo (P=.010), which is equivalent to a … Aetna considers crizanlizumab-tmca (… Eligible patients were diagnosed with sickle cell disease (any genotype including HbSS, HbSC, HbS beta 0-thalassemia, HbSbeta+thalassemia, and others). Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. 4. These analyses should be interpreted with caution as the data are from a noncomparative post hoc subgroup analysis and not powered to detect statistical significance or superiority of ADAKVEO over placebo. Be the first to rate this post. ADAKVEO® (crizanlizumab-tmca) is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients, aged 16 years and older, with sickle cell disease. Watch Ifeyinwa (Ify) Osunkwo, MD, MPH, discuss key points of the pivotal trial design to help you determine the clinical profile of ADAKVEO. We’re moving on! * The study included 198 patients evaluated at 60 study centers, the majority of which were located in the United States (51 centers with 151 study patients)1-3†, Prespecified, noncomparative subgroup analysis evaluated the annual rate of VOCs with or without hydroxyurea. color: #333 !important; The CHMP opinion was based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo (P=.010), equivalent to a 45% reduction. font-weight: normal; In the SUSTAIN clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed in 2 (3%) patients treated. The EC approval is based on a positive opinion by the Committee for Medicinal Products for Human Use (CHMP). Initial: 5 mg/kg at week 0 and week 2 ii. .uso-brand-details h5 { Novartis Pharmaceuticals Corp; February 2020. For precertification of crizanlizumab (Adakveo), call (866) 752-7021, or fax (866) 267-3277. “The approval of Adakveo marks a new era in the treatment of sickle cell disease, a genetic condition that places an extraordinary burden of unpredictable pain crises on patients and their families,” said Susanne Schaffert, PhD, president of Novartis Oncology. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. Discontinue ADAKVEO infusion for severe reactions and institute appropriate medical care. In the 52-week SUSTAIN study, ADAKVEO was proven to reduce the frequency of VOCs 1 Significant 45% (1.63 vs 2.98) reduction in the median annual rate of VOCs vs placebo 1,2 * Reduction in the frequency of VOC s was observed regardless of VOC baseline … Per-protocol population is a subset of the ITT patient population who received at least 12 of the 14 planned doses of ADAKVEO (n=40) or placebo (n=41), completed a visit at least 14 days after final dose of study drug, and had no major protocol violations. Basel, October 30, 2020 — Novartis today announced that the European Commission (EC) has approved Adakveo (crizanlizumab) for the prevention of recurrent vaso-occlusive crises (VOCs), or pain crises, in patients with sickle cell disease aged 16 years and older. The key secondary end point in the SUSTAIN study was defined as the annual rate of days a patient was hospitalized, including those related to VOCs. Data on file. Kutlar A, Kanter J, Liles DK, et al. The SUSTAIN Study Video Summary of Original Article Feb 02, 2017 Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease K. I. Ataga and Others This trial’s purpose is to find an appropriate dose for pediatric patients; study site and contact information can be found here. That puts the therapy’s list price, which patients typically do not pay, at $7,071 to $9,428 per month or between $84,852 and $113,135 each year. In SCD, P-selectin promotes the sticking of sickle-shaped red blood cells to each other and to the walls of blood vessels, obstructing the vessels and increasing the risk of VOCs. The FDA previously granted Adakveo orphan drug and breakthrough therapy status, and its approval review was given priority. margin-left: 0px !important; Adakveo’s recommended dosing is 5 mg/kg by intravenous infusion over a period of 30 minutes for a first infusion and again two weeks later, then once every four weeks thereafter. 3. Adakveo should be administered by a healthcare professional and may be given with or without hydroxyurea. “We are excited to have a new medicine that may help many of the thousands of people.”. Join us at www.hcp.novartis.com—our new location for health care professionals to find product, access, and medical information. margin-top: 20px !important; Monitor patients for signs and symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath or wheezing. ADAKVEO® is indicated to reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease. An icon used to represent a menu that can be toggled by interacting with this icon. Novatis put Adakveo’s wholesale list price at$ $2,357 a vial, and estimates are that most patients will need three or four vials for each month’s treatment. Enrolled patients, ages 16 and older, were randomly assigned either to an intravenous infusion of Adakveo at one of two doses (2.5 mg/kg or 5 mg/kg) or to a placebo every other week for the first weeks, and then every four weeks over about one year of treatment. A monoclonal antibody, Adakveo works by binding and blocking the activity of P-selectin, a protein found on the surface of endothelial cells that make up the lining of blood vessels. You are now leaving the Novartis site and moving to an external website independently operated and not managed by Novartis Pharmaceuticals Corporation. References: 1. In addition, interference with Data on file. Copyright © 2013-2021 All rights reserved. Results reported at 2 weeks were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error, In patients on ADAKVEO with hydroxyurea, time to first VOC was 2.4 months vs 1.2 months in those on placebo with hydroxyurea (HR=0.58; 95% CI: 0.35, 0.96), In patients on ADAKVEO without hydroxyurea, time to first VOC was 5.7 months vs 2.9 months in those on placebo without hydroxyurea (HR=0.39; 95% CI: 0.20, 0.76), Led to a health care visit, which captured all acute episodes of pain with no other cause than a vaso-occlusive event that required a medical facility visit (ER, clinic, hospital, or local physician visit), Required treatment with oral or parenteral opioids or parenteral NSAIDs, Included events such as acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism, Were adjudicated by a third-party committee, 62% of patients were on hydroxyurea and still had experienced 2 to 10 VOCs in the previous 12 months, Patients were on hydroxyurea for at least 6 months and on a stabilized dose for at least 3 months prior to the study. SCD, sickle cell disease; NSAIDs, non-steroidal anti-inflammatory drugs. “Patients with sickle cell disease often face unique challenges, and have long suffered silently through unimaginable pain crises,” said Beverley Francis-Gibson, president and CEO of the Sickle Cell Disease Association of America. “We know this drug can decrease the frequency of sickle cell pain crises in a significant and clinically meaningful way,” Kenneth Ataga, MD, director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center, and principal investigator of the SUSTAIN trial, said in Novartis’ release. An open-label Phase 2 trial (NCT03474965) of crizanlizumab in up to 100 children with sickle cell disease who have at least one VOC in the past year is now recruiting infants and children, starting at age 6 months, at sites in the U.S., Canada, Europe, and elsewhere. Interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO, in particular, when blood samples were collected in tubes containing EDTA. The efficacy of ADAKVEO® (crizanlizumab-tmca) was evaluated based on the annual rate of VOCs in patients (16 to 63 years of age) with SCD in a pivotal, phase 2, 52-week, randomized, multicenter, placebo-controlled, double-blind study. Data on file. Adakveo is proven and/or medically necessary to reduce the frequency of vasoocclusive crises in patients with sickle cell disease who meet all the following criteria: 1-3. 2019;94(1):55-61. Monitor patients for signs and symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, or shortness of breath or wheezing. Copyright © 2020 Novartis Pharmaceuticals Corporation. Based on animal data, ADAKVEO has the potential to cause fetal harm when administered to a pregnant woman. Tagged Adakveo, crizanlizumab, FDA approval, Novartis, SUSTAIN study, vaso-occlusive crises, VOCs. .uso-brand-details .footnotes { Or click OK to continue. } Watch Nirmish R. Shah, MD, describe the clinical data for ADAKVEO, and a hypothetical patient case study. The per-protocol population was analyzed according to the randomized treatment arm and not powered to show statistical significance. Adakveo’s recommended dosing is 5 mg/kg by intravenous infusion over a period of 30 minutes for a first infusion and again two weeks later, then once every four weeks thereafter. 2. Adakveo is indicated to treat adults and adolescents, starting at age 16, and should soon be available to patients in the U.S., Novartis said in its press release. color: #d57800 !important; The agency announced its decision two months ahead of its priority review action date, allowing SCD patients in the U.S. to have access to the medication sooner. Full prescribing information for Adakveo, including recommended dosing schedules and safety warnings, can be found here. That dose was shown to lower the frequency of annual VOCs in SCD patients in the company’s Phase 2 SUSTAIN (NCT01895361) trial. Maintenance: 5 mg/kg every 4 weeks beginning at week 6 . Note: Site of Care Utilization Management Policy applies. font-family: arial, sans-serif !important; 1 Adakveo can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is … 2017;376(5):429-439. *Annual rate of VOCs leading to a health care visit (ER, clinic, hospital, or local physician visit).1,4. Table 1:Adverse Reactions(≥10%)in PatientsReceiving ADAKVEO With a Difference Between Arms of >3% Compared to Placebo in SUSTAIN Adverse Reactions ADAKVEO 5 mg/kg N = 66 n (%) Placebo N= 62 n (%) The CHMP opinion was based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of … Use of website is governed by the Terms of Use and Privacy Policy. line-height: 1.2; In the SUSTAIN clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO 5 mg/kg. An early separation of the time to first VOC was observed at Week 2 with ADAKVEO.