FDA approves Adakveo to reduce pain crises from sickle cell disease
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The FDA approved crizanlizumab to reduce the frequency of pain crises among people with sickle cell disease.
Crizanlizumab (Adakveo, Novartis) — indicated for patients ages 16 or older — is a humanized anti-P-selectin monoclonal antibody administered via monthly infusion. It binds to P-selectin on the surface of platelets and endothelium in the blood vessels.
The agent has been shown to inhibit interactions between red blood cells, sickled red blood cells, endothelial cells, platelets and leukocytes, preventing these cells from being able to bind to P-selectin, a key driver of the vaso-occlusive process.
The FDA — which previously granted priority review to crizanlizumab for this same indication — based the approval on results of the randomized SUSTAIN trial, which included 198 patients with sickle cell disease and a history of two to 10 vaso-occlusive crises in the 12 months prior to study enrollment.
Researchers randomly assigned patients to crizanlizumab 5 mg/kg (n = 67), crizanlizumab 2.5 mg/kg (n = 66) or placebo (n = 65) administered over 30 minutes via IV infusion in week 0, week 2 and every 4 weeks thereafter. Total treatment duration was 52 weeks.
The annual rate of vaso-occlusive crises leading to a health care visit served as the primary outcome measure. Secondary endpoints included annual rate of days hospitalized, time to first vaso-occlusive crisis leading to a health care visit and the number of patients who did not experience a vaso-occlusive crisis.
Results showed crizanlizumab significantly lowered the median annual rate of vaso-occlusive crises compared with placebo (1.63 vs. 2.98; P = .01). Median time to first vaso-occlusive crisis was 4.1 months with crizanlizumab and 1.4 months with placebo.
Patients assigned crizanlizumab were more than twice as likely to be free of vaso-occlusive crises during the study period (36% vs. 17%). They also spent fewer days in the hospital (4 vs. 6.87).
Researchers observed reduced frequency of vaso-occlusive crises among crizanlizumab-treated patients regardless of sickle cell disease genotype or hydroxyurea use.
“We know this drug can decrease the frequency of sickle cell pain crises in a significant and clinically meaningful way,” Kenneth I. Ataga, MD, principal investigator of the SUSTAIN trial and director of Center for Sickle Cell Disease at University of Tennessee Health Science Center at Memphis, said in a Novartis-issued press release. “The approval of crizanlizumab is an important advancement for people living with this very difficult condition.”
The most common adverse reactions among crizanlizumab-treated patients included nausea (18%), arthralgia (18%), back pain (15%) and pyrexia (11%).
“Patients with sickle cell disease often face unique challenges, and have long suffered silently through unimaginable pain crises,” Beverley Francis-Gibson, president and CEO of Sickle Cell Disease Association of America, said in the release. "We are excited to have a new medicine that may help many of the thousands of people living with sickle cell disease by reducing the frequency of these potentially dangerous and painful episodes.”