Real-World Data on the Occurrence of Vaso-Occlusive Crises (VOCs) in Patients with Sickle Cell Disease (SCD) and a High Baseline Disease Burden Treated with Crizanlizumab: Results from a Managed Access Program (MAP)

Abstract Background: VOCs are the hallmark of SCD and can lead to serious complications and organ damage. P-selectin, a cell adhesion protein, plays a central role in the multicellular interactions that can lead to VOCs. Crizanlizumab, a first-in-class humanized monoclonal antibody that targets P-selectin, is approved in several regions to prevent/reduce VOC burden for patients (pts) with SCD aged ≥16 years. Pts in some countries can obtain early access to crizanlizumab before health authority approval via a MAP (NCT03720626); first pt enrolled in June 2018. Aim: To describe the proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab in the MAP (in countries where publication of these data is allowed). Methods: The MAP was designed to provide access to crizanlizumab for SCD pts with serious or life-threatening disease for which no comparable or satisfactory alternative to crizanlizumab was available as treatment in their country. Other eligibility criteria included: aged 16-70 years (18-70 years in Italy); history of VOCs as assessed by the treating physician (including recurrent VOCs while receiving hydroxyurea [HU], L-glutamine or other therapies); and not eligible for a crizanlizumab clinical trial. At baseline, treating physicians were asked about their pts' disease burden in the 12 months prior to requesting access to crizanlizumab (eg frequency of home- or healthcare-managed VOCs and opioid use for VOC management). The proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab are described overall and stratified by SCD genotype and history of HU use. Results: Treating physicians made requests for initial access to crizanlizumab for 146 pts eligible for this analysis. Most of these pts were from Brazil (n=105; 72%), with the remainder residing in Italy, Spain, Israel, Canada, Portugal and Switzerland. Of the 144 pts with baseline data (missing, n=2), 142 (99%) had ≥1 home-managed VOC (median [interquartile range; IQR] of 6 [4‒8.5] VOCs) and 137 (95%) had ≥1 healthcare-managed VOC (median [IQR] of 3 [2‒5] VOCs) in the 12 months before entry into the MAP. Opioids were taken for VOC management by 92% of pts in the 12 months prior to baseline (n=132/144); the most common was morphine (n=57/132; 43%). As of June 2021, 102 of the 146 pts with initial requests had received crizanlizumab for ≥6 months and had resupply requests submitted by their physicians. For these 102 pts, median (IQR) age was 33 (25-40) years, 62% were female, 47% were of African American ethnicity, the genotype was HbSS in 79%, and a history of HU use was reported in 45% of these pts. Eleven pts (5%) discontinued crizanlizumab during the 6 months of treatment reported in this analysis. Of the 102 pts with data available 6 months post-crizanlizumab initiation, 46 (45%) reported 0 home-managed VOCs (median [IQR] of 1 [0‒2] VOC) and 62 (61%) reported 0 healthcare-managed VOCs (median [IQR] of 0 [0‒1] VOCs) during this time period. The proportions of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab stratified by SCD genotype and history of HU use are shown in Figure 1. Clinicians participating in the MAP anecdotally reported improvement in certain clinical complications (eg leg ulcers and priapism), reduced frequency of hospitalizations, shorter lengths of hospital stay and reduced use of opioids in some pts after crizanlizumab treatment. Adverse events were consistent with those reported in other crizanlizumab studies. Limitations: The difference in time periods for which data are available (ie 12 months for baseline data vs 6 months for post-treatment initiation data) precludes a comparison of data pre- and post-initiation of crizanlizumab in this analysis. Information about HU use was not provided for all pts, therefore the proportion of pts with a history of HU use in this analysis could be higher than reported. Conclusion: Pts participating in the crizanlizumab MAP had a high burden of home- and healthcare-managed VOCs at baseline despite many pts reporting a history of HU use; almost all required opioids for VOC management. Findings from this analysis looking at the proportion of pts with 0 home- or 0 healthcare-managed VOCs after 6 months of treatment with crizanlizumab are promising, although additional data with ≥12 months of exposure are required to compare VOC burden on treatment with that reported here at baseline. Figure 1 Figure 1. Disclosures Cançado: Novartis: Consultancy. Colombatti: NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees. Quarta: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Celgene: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Sanofi - Genzyme: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Blue Bird Bio: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Takeda: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; speaker at conferences; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at conferences. DeBonnett: Novartis Pharmaceuticals Corporation: Current Employment. Soliman: Novartis: Current Employment. Sarkar: Novartis: Current Employment. Pinto: Novartis: Consultancy; Global Blood therapeutics (GBT): Consultancy; EMS, Brazil: Consultancy.

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