Results from the SUSTAIN trial found that the monoclonal antibody crizanlizumab, which targets anti-P-selectin, reduces the frequency of pain crises by nearly half, compared with placebo, in adolescents and adults with sickle cell disease (SCD). These results suggest that crizanlizumab may offer another treatment option for patients with SCD who cannot tolerate or are reluctant to take hydroxyurea (the only U.S. Food and Drug Administration [FDA]-approved treatment for SCD complications) or those for whom hydroxyurea is ineffective.
The SUSTAIN trial enrolled 198 SCD patients (age range = 16-65 years) who had experienced at least two and as many as 10 pain crises during the previous year. Patients were randomly assigned to one of three treatment arms: 5 mg/kg of crizanlizumab (n=67), 2.5 mg/kg of crizanlizumab (n=66), or placebo (n=65), administered intravenously once monthly. Patients in all arms received an initial loading dose, a dose 14 days later, and then a dose every four weeks through week 50, for a total of 14 doses.
"Pain crises are a significant morbidity for patients with SCD, and these episodes are unpredictable, varying from very mild to extremely severe," lead study author Kenneth I. Ataga, MD, MBBS, of the University of North Carolina at Chapel Hill, told ASH Clinical News. "We don't have very many options for SCD, other than hydroxyurea, so seeing this type of effect with a new drug is impressive."
After one year, compared with placebo, the median annual rate of pain crises was reduced by 47 percent with the 5 mg/kg dose of crizanlizumab (1.6 vs. 3.0; p=0.010) and reduced by 33 percent with the 2.5 mg/kg dose (2.0 vs. 3.0; p=0.180). In addition, the median times between first and second pain crises were prolonged in patients treated with 5 mg/kg of crizanlizumab, compared with placebo: 4.1 versus 1.4 months (p=0.001) and 10.3 versus 5.1 months (p=0.022), respectively.
"Although some side effects were reported, overall the drug seemed to be well tolerated," said Dr. Ataga. "I believe it will make a significant difference in patients' lives."
Compared with placebo, 5 mg/kg of crizanlizumab also reduced the annual rate of uncomplicated pain crises (defined as pain crises other than acute chest syndrome, priapism, and hepatic or splenic sequestration) by 62 percent (median = 1.1 vs. 2.9; p=0.015) and the annual rate of days hospitalized by 42 percent (median = 4.0 vs. 6.9; p=0.450).
Compared with patients in the placebo group, patients in an active-dose group experienced more arthralgia, pruritus, vomiting, chest pain, diarrhea, road traffic accident, fatigue, myalgia, musculoskeletal chest pain, abdominal pain, influenza, and oropharyngeal pain (all adverse events occurred in â‰¥5% of patients).
Five deaths occurred during the study: two at the 5.0 mg/kg dose, one at the 5.0 mg/kg dose, one at the 2.5 mg/kg dose, and two in the placebo group. None of these deaths were considered related to the study drug.
Long-term, follow-up studies will be needed to establish whether the drug affects survival and if it is effective in younger patients. "This study was restricted to patients between 16 and 65 years old, so we are interested in preforming this study in young children because they have pain crises as well," said Dr. Ataga.
Ataga KI, Kutlar A, Kanter J, et al. SUSTAIN: a multicenter, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of SelG1 with or without hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises. Abstract #1. Presented at the 2016 ASH Annual Meeting, December 4, 2016; San Diego, California.