Swedish Orphan Biovitrum AB is an international biopharmaceutical company dedicated to treatments in the areas of haematology, immunology and specialty care, based in Stockholm, Sweden. In 2020 it had a revenue of SEK 15.261 billion and 1,509 employees.
C3 glomerulopathy (C3G) is a rare complement-mediated kidney disease. Pegcetacoplan [targeted complement 3 (C3)/C3b inhibitor] and iptacopan (factor B inhibitor) target the complement system and are approved for treatment of C3G in adults and adolescents (pegcetacoplan) or adults only (iptacopan). Currently, no head-to-head randomized controlled trials (RCTs) have assessed their relative efficacy. Indirect treatment comparisons (ITCs) were conducted using the Bucher (primary analysis—preserves randomization) and matching-adjusted indirect comparison (MAIC; supportive analyses—adjusts for trial differences) methodologies and data from two similarly designed, placebo-controlled, Phase III RCTs in C3G/primary immune-complex membranoproliferative glomerulonephritis [VALIANT (NCT05067127)] and C3G only [APPEAR-C3G (NCT04817618)]. Relative efficacy was assessed at 6 months (anchored Bucher and MAIC) and 12 months (anchored Bucher/MAIC plus unanchored MAIC). At 6 months, the Bucher analysis demonstrated pegcetacoplan was associated with a significantly greater reduction in urine protein–creatinine ratio (UPCR) relative to baseline versus iptacopan [mean difference −50.90
OBJECTIVE:DISSOLVE I and II examined the efficacy and safety of nanoencapsulated sirolimus (NAS) plus pegadricase (NASP) in patients with uncontrolled gout (UG). METHODS:In these double-blind, placebo-controlled Phase 3 trials of NASP, patients were randomized 1:1:1 to infusions of high-dose (HD) or low-dose (LD) NAS plus pegadricase (HD NASP, LD NASP, respectively) or placebo, given every 4 weeks for 6 doses. The primary endpoint was proportion of patients with serum urate (SU) < 6 mg/dL for ≥ 80% of the time during Weeks 21-24. Secondary endpoints included health-related quality of life, tophus resolution, tender joints, and gout flares. Safety was also assessed. RESULTS:Overall, 265 patients received HD NASP, LD NASP, or placebo. SU response during weeks 21 to 24 was significantly higher with NASP than with placebo (HD NASP: 51%; LD NASP: 43%; placebo: 8%; P < 0.0001 for both doses vs placebo). Common adverse events included gout flares (HD NASP: 42.5%; LD NASP: 44.3%; placebo: 43.3%), infections (HD NASP: 23.0%; LD NASP: 18.2%; placebo: 16.7%), and stomatitis (HD NASP: 9.2%; LD NASP: 3.4%; placebo: 0%). Infusion reactions within 1 hour were infrequent (4%) in NASP-treated patients. During weeks 1 to 12, the proportion of patients with flares was similar between NASP- and placebo-treated patients; thereafter, it decreased in NASP-treated patients but remained unchanged with those receiving the placebo. CONCLUSION:NASP treatment resulted in a significantly higher proportion of patients with complete SU response during weeks 21 to 24 compared with placebo and was generally well tolerated. NASP, an every-4-week treatment, can markedly alleviate disease burden in patients with UG.
Objectives: To assess effectiveness of recombinant factor VIII Fc fusion protein (efmoroctocog alfa; referred to herein as rFVIIIFc) prophylaxis in people with haemophilia A (PwHA) stratified by age, body mass index (BMI), disease severity and inhibitor history included in the A-SURE (NCT02976753) and PREVENT (NCT03055611) real-world studies. Methods: PwHA receiving at least one prescription of rFVIIIFc and ≥3 months follow-up during the prospective periods were included. Post-hoc analyses were performed for the overall analysis population and subgroups based on age, BMI, disease severity and those with and without previous inhibitors. Effectiveness endpoints were annualised bleeding rate (ABR), annualised joint bleeding rate (AjBR), injection frequency and factor consumption in the prospective period. Results: Overall, 333 PwHA were analysed. ABRs and AjBRs, generally, were low across the different subgroups (range of medians, 0.0–0.6 for both ABRs and AjBRs, except for ABRs in PwHA aged ≥65 years). Injection frequencies (n injections/week) were comparable across subgroups (range of medians, 2.0–2.3), and factor consumption was generally similar (range of medians, 68.3–100.0 international units/kg/week), though with slightly higher factor consumption in paediatric PwHA and lower consumption in the overweight or obese BMI groups. Conclusions: These post-hoc analyses support the effectiveness and, therefore, use of rFVIIIFc prophylaxis in PwHA across all ages, BMI categories, severities and for those with a history of inhibitors. Trial registration: ClinicalTrials.gov. A-SURE: NCT02976753; PREVENT: NCT03055611
