Novartis said a post-hoc analysis from a mid-stage study published in the American Journal of Hematology shows that more than twice as many patients with sickle-cell disease taking crizanlizumab did not experience a vaso-occlusive crisis (VOC), compared with placebo, specifically among those with a history of two to 10 VOCs in the year prior. The company, which had previously anticipated filing the humanised anti-P-selectin monoclonal antibody with US regulators by the end of 2018, now says discussions with health authorities continue and an FDA submission is expected next year instead.
"The insights gained from this analysis and others from the SUSTAIN study, strengthen our belief that crizanlizumab may become an important new therapeutic option for sickle-cell patients," said Samit Hirawat, global head of oncology drug development at Novartis.
The post hoc analysis reviewed 52-week results from 132 patients with sickle-cell disease who were randomly assigned to treatment with crizanlizumab or placebo, with or without concomitant use of hydroxyurea therapy. Patients had experienced at least two VOCs in the prior 12 months, with 62.9 percent of them having experienced two to four events and 37.1 percent with five to 10 events.
Primary results from the SUSTAIN trial, which were published in the NEJM in early 2017, had shown that crizanlizumab reduced the median annual rate of sickle-cell pain crises by 45.3 percent compared to placebo in patients with or without hydroxyurea therapy. The post-hoc analysis showed that 35.8 percent of crizanlizumab-treated patients did not experience a VOC, compared with 16.9 percent for placebo.
Subgroups evaluated in the analysis showed that among patients who experienced between two and four VOCs in the prior year, 40.5 percent of those in the crizanlizumab group had no VOCs at 52 weeks, compared to 24.4 percent for placebo. Among patients with five to 10 VOCs, 28 percent of crizanlizumab-treated subjects and 4.2 percent of those on placebo experienced no VOCs during the study.
Meanwhile, the VOC-free rates for patients with the HbSS genotype, the most common genotype in sickle-cell disease, were 31.9 percent in the crizanlizumab group and 17 percent for placebo. Among patients who received concomitant hydroxyurea, the VOC-free rates in these two groups were 33.3 percent and 17.5 percent, respectively.
Last December, Novartis reported on another subgroup analysis of the SUSTAIN trial showing that crizanlizumab, formerly known as SEG101, approximately doubled the time to first on-treatment sickle-cell pain crisis. At the time, the company noted that results were consistent across patient subgroups despite differences in disease severity, genotype or background therapy.
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