- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. (Pubmed Central) - Aug 30, 2019
P3
There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Ultomiris IV (ravulizumab IV) / Alexion Pharma
Therapeutic complement inhibition in neuroinflammatory diseases (Hall F) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_1455;
a Phase 3, prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-center, time-to-event trial evaluated the safety and efficacy of Eculizumab for patients with relapsing NMOSD; 3. A long-term safety and efficacy of Eculizumab is being performed in patients with relapsing NMOSD who have completed the initial Phase 3.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Roche, Biogen
Autologous Hematopoietic Stem Cell Transplant in Patients with Severe Refractory Neuromyelitis Optica Spectrum Disease: The Ottawa Experience (Hall A) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_1404;
Treatment options have broadened from relying on high-dose steroids and steroid sparing agents such as mycophenolate mofetil and azathioprine to the inclusion of more potent biological agents such as rituximab, tocilizumab and eculizumab, but so far treatments that have a durable impact on disease activity are lacking. Although aHST does have an increased risk of significant medical complications, given the unique potential for a sustained response, it may be a valid approach for patients with severe refractory NMOSD.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Long-term safety and effectiveness of eculizumab in neuromyelitis optica spectrum disorder (Hall A) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_1400;
P3
Conclusion In this long-term safety and effectiveness analysis, eculizumab was well tolerated and the AEs reported were consistent with its established safety profile in other indications. The percentage of relapse-free patients remained high (~94%) through 192 weeks.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Roche, Biogen
Impact of eculizumab on disability measures in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: phase 3 PREVENT study (Poster Exhibition) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_1089;
For eculizumab compared with placebo, mean change in EDSS from baseline to study end was -0.18 (standard deviation [SD] 0.814) versus 0.12 (SD 0.945); p =0.0597, for mRS, mean change was -0.2 (0.72) versus 0.1 (SD 0.75); p =0.0154 and for HAI, mean change was -0.4 (SD 1.08) versus 0.5 (SD 1.61); p =0.0002. The distribution for the change from baseline to end of study in EDSS score showed 51.0% of the eculizumab-treated patients and 42.6% of the placebo-treated patients had no change, 29.2% of the eculizumab-treated patients and 29.8% of the placebo-treated patients had a ≥0.5-point improvement in EDSS score, while 19.8% of the eculizumab-treated patients and 27.7% of the placebo-treated patients had a ≥0.5-point worsening in EDSS score.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Roche, Biogen
Impact of eculizumab on reported quality of life in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: findings from the PREVENT study (Poster Exhibition) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_740;
P3
At baseline, mean physical component scores (PCS) for eculizumab and placebo were 38.6 (9.8) and 36.9 (10.8), respectively, and changed from baseline to EOS by 3.36 (7.73) and 0.70 (8.25), respectively (p =0.0210). At baseline, mean mental component scores (MCS) for eculizumab and placebo were 47.0 (12.5) and 44.0 (11.4), respectively, and changed from baseline to EOS by 0.45 (10.60) and −0.06 (11.79), respectively (p =0.2942).
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Roche, Biogen
Subgroup analyses from the Phase 3 PREVENT study in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (Poster Exhibition) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_698;
P3
Pre-specified IST subgroups were: corticosteroids alone; azathioprine (AZA) with/without corticosteroids; mycophenolate mofetil (MMF) with/without corticosteroids; other IST; no IST; and historic rituximab use...The proportions of patients with an adjudicated relapse in the eculizumab and placebo groups, respectively, among those from Europe (n = 51) were 1/32 (3.1%) and 12/19 (63.2%); in those from Asia-Pacific (n = 48), proportions were 1/35 (2.9%) and 5/13 (38.5%), and in those from the Americas (n = 44), proportions were 1/29 (3.4%) and 3/15 (20.0%). Conclusions The robust treatment effect of eculizumab on relapse risk reduction was observed across all pre-specified subgroups, including IST use as well as no IST use, geographic region, age, race and gender.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
New emerging treatments in NMOSD (Hall C) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_156;
Collectively, these studies support the general observation that improved understanding of pathogenesis of NMOSD and rational choice of immunotherapies for study substantially increased the prospect of demonstrating robust efficacy in reducing attacks. How to integrate new treatments into current recommendations for long term treatment, whether or not future placebo-controlled studies are ethical and whether future head-to-head studies are feasible are important issues emerging from these clinical trials.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Soliris (eculizumab) / AstraZeneca
Enrollment closed, Trial primary completion date: DUET: The De-novo Use of Eculizumab in Presensitized Patients Receiving Cardiac Transplantation (clinicaltrials.gov) - Aug 22, 2019
P4, N=20, Active, not recruiting,
The trial is registered with EudraCT (#2009-016966-97) and www.clinicaltrials.gov (#NCT01303952). Enrolling by invitation --> Active, not recruiting | Trial primary completion date: Dec 2018 --> Aug 2019
- |||||||||| Voydeya (danicopan) / AstraZeneca, Soliris (eculizumab) / AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date, Monotherapy: Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab (clinicaltrials.gov) - Aug 19, 2019
P2, N=12, Active, not recruiting,
Enrolling by invitation --> Active, not recruiting | Trial primary completion date: Dec 2018 --> Aug 2019 Recruiting --> Active, not recruiting | Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Jun 2019 --> Sep 2019
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Invasive meningococcal disease in patients with complement deficiencies: a case series (2008-2017). (Pubmed Central) - Aug 16, 2019
In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Ocular thrombotic microangiopathy in atypical hemolytic-uremic syndrome (a clinical case study) (Pubmed Central) - Aug 15, 2019
A typical manifestation of this ocular lesion in this disease is bilateral Purtscher-like retinopathy. Timely diagnostics of atypical hemolytic-uremic syndrome, including ophthalmologic examination, determines the early start of a highly effective pathogenetic therapy with complement inhibitor eculizumab.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Trial primary completion date: CHAPLEOMIC: Transcriptome and Metabolic Analyses of CHAPLE Disease (clinicaltrials.gov) - Aug 14, 2019
P=N/A, N=60, Recruiting,
Timely diagnostics of atypical hemolytic-uremic syndrome, including ophthalmologic examination, determines the early start of a highly effective pathogenetic therapy with complement inhibitor eculizumab. Trial primary completion date: Jun 2019 --> Sep 2019
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: Shiga Toxin as a Potential Trigger of CFHR1 Deletion-Associated Thrombotic Microangiopathy. (Pubmed Central) - Aug 9, 2019
Here we describe the presentation and management of an individual with CFHR1 deletion-associated TMA also found to have a positive stool Shiga toxin. We discuss the significance of Shiga toxin in serving as a trigger for development of TMA in an individual predisposed to development of TMA due to presence of a homozygous deletion in CFHR1.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: New Complement Therapeutics in Complement-Related Diseases (Pubmed Central) - Aug 8, 2019
...In 2007, eculizumab (ECZ), an anti-C5 (complement factor 5) monoclonal antibody, was approved as a drug for paroxysmal nocturnal hemoglobinuria (PNH) in the United States...The success of ECZ created an opportunity for drug companies to develop new therapeutics targeting the complement system; development of complement therapeutics is now a major venture of pharmaceutical companies worldwide. Here, I will provide an outline of the approved complement therapeutics and those that are in development and clinical trial phase currently.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Eculizumab Treatment for Refractory Generalized Myasthenia Gravis (Pubmed Central) - Aug 8, 2019
Recently, complement inhibitor, the humanized monoclonal anti-C5 antibody eculizumab, complement inhibitor, was approved for patients with anti-AChR antibody-positive generalized refractory MG in Japan. In this review, we focus on the role of complements in the pathogenesis of MG and the action mechanism, efficacy, and future prospects of eculizumab.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Current Status and Prospects of Complement-Targeting Therapy for Neuromyelitis Optica (Pubmed Central) - Aug 8, 2019
In this article, we review the relevance of the complement system in the pathogenesis of NMO. Additionally, we review the current status and prospects of the complement-targeting therapy for NMO, including the clinical trials of eculizumab and C1 inhibitor for NMO, and the experimental studies on C1 inhibition by monoclonal antibodies.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Complement-Mediated Mechanism and Complement Inhibitors in Guillain-Barré Syndrome (Pubmed Central) - Aug 8, 2019
A recent Japanese randomized controlled trial with eculizumab, a monoclonal antibody against the complement C5, indicated that eculizumab might improve the outcomes of GBS patients at six months from onset. In future, the prognosis of severe GBS cases may possibly be improved by a novel therapy targeting the complement.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
A Case of Budd-Chiari in the Setting of Paroxysmal Nocturnal Hemoglobinuria (Exhibit Halls 3 and 4 (Street Level)) - Aug 8, 2019 - Abstract #ACG2019ACG_2962;
With new diagnosis of PNH, he was started on Eculizumab with Hematology follow up...In a patient with high concern for Budd-Chiari and unremarkable noninvasive testing, hepatic venography is a helpful diagnostic tool. In a patient with significant thrombosis such as this with a history of aplastic anemia, it is important to consider PNH.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: Myasthenia gravis: the role of complement at the neuromuscular junction. (Pubmed Central) - Aug 1, 2019
Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. Direct complement inhibition could preserve NMJ physiology and muscle function in patients with anti-AChR+ gMG.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Seizure as the Presenting Symptom for Atypical Hemolytic Uremic Syndrome. (Pubmed Central) - Aug 1, 2019
The etiology of approximately 60% of patients with aHUS can be attributed to genetic mutations in complement regulators including factor H, membrane cofactor protein, factor I, activator factor B, or C3. Although previously treated with plasma transfusion and immunosuppressants, eculizumab is a newer treatment that has been changing prognosis and management of aHUS, but it should be administered within 48 h of symptom onset for best efficacy.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: Pharmacotherapy for Neuromyelitis Optica Spectrum Disorders: Current Management and Future Options. (Pubmed Central) - Jul 19, 2019
The numerous agents under development are the result of a major collaborative effort all over the world. After the considerable progress on diagnosis, we are now close to class I evidence for a therapeutic effect of several drugs in NMO spectrum disorders, most notably with the anti-interleukin-6 receptor antibody (satralizumab) and anti-complement-5 antibody (eculizumab).
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: A small-molecule inhibitor of C5 complement protein. (Pubmed Central) - Jul 18, 2019
The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment. (Pubmed Central) - Jul 11, 2019
Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Paroxysmal nocturnal hemoglobinuria and thrombosis in the era of eculizumab (Pubmed Central) - Jul 11, 2019
These facts strongly suggest that the main cause of thrombosis in PNH is complement activation and/or hemolysis. In this review, the pathophysiology of thrombosis in PNH is discussed in the context of observations in PNH patients treated with eculizumab.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Management of paroxysmal nocturnal hemoglobinuria: an update (Pubmed Central) - Jul 7, 2019
Therefore, it is important to strategize effective ways to tackle these issues occurring during eculizumab treatment. In Japan, it is an urgent priority to reach a consensus for managing IMD in patients treated with eculizumab and for establishing protocols for prophylaxis to prevent meningococcal infection.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: Bidirectional graft-host hematological traffic in liver transplantation. (Pubmed Central) - Jun 28, 2019
We speculate that combined bone marrow and liver transplantation would be a better option for recipients with FVIII inhibitors or PNH. Replacement of liver graft endothelium with recipient cells is common and may explain relative transplant tolerance that is believed to occur with liver transplantation.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Biomarker, Journal: Glucose-6-Phosphate Dehydrogenase Deficiency Mimicking Atypical Hemolytic Uremic Syndrome. (Pubmed Central) - Jun 28, 2019
...The patient was started initially on plasma exchange and subsequently eculizumab therapy, after which his kidney function rapidly improved...This case of G6PD deficiency presented with a phenotype clinically indistinguishable from complement-mediated aHUS. We recommend that G6PD deficiency be included in the differential diagnosis of patients presenting with aHUS and suggest measuring erythrocyte G6PD concentrations in these patients.
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