- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: CFH and CFB mutations in Shiga toxin-associated haemolytic uraemic syndrome in a 6-year-old boy. (Pubmed Central) - Jun 16, 2021
However, several issues remain to be explained including the effect of genetic and environmental factors in modifying susceptibility to develop aHUS in some patients following STEC infection. Abbreviations: aHUS: atypical haemolytic uraemic syndrome; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; ASO: anti-streptolysin O; BUN: blood urea nitrogen; CFB: complement factor B; CFH: complement factor H; EHEC: enterohaemorrhagic Escherichia coli; MCP: membrane co-factor protein; PD: peritoneal dialysis; STEC: Shiga toxin-producing Escherichia coli; STX 1-2: Shiga toxins 1-2.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: New insights into the pathogenesis of Streptococcus pneumoniae-associated hemolytic uremic syndrome. (Pubmed Central) - Jun 16, 2021
Recent observations indicate that although neuraminidase activity and exposure of the T-antigen are necessary for development of P-HUS, they are not sufficient; activation of the alternate pathway of complement may also contribute. It is unclear, however, whether or not eculizumab and/or plasmapheresis are of value.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Meningococcal Serogroup B Disease in Vaccinated Children. (Pubmed Central) - Jun 16, 2021
In 2 cases, the antibodies induced by 4CMenB likely were not effective against the isolated strains. A high level of suspicion for IMD seems advisable regardless of the patient's vaccination history.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Treatment-resistant nephrotic syndrome in dense deposit disease: complement-mediated glomerular capillary wall injury? (Pubmed Central) - Jun 16, 2021
A high level of suspicion for IMD seems advisable regardless of the patient's vaccination history. These cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Paroxysmal nocturnal haemoglobinuria (PNH): novel therapies for an ancient disease. (Pubmed Central) - Jun 16, 2021
Recently a derivative of eculizumab with more favourable pharmacokinetics has been introduced. In view of the fact that these agents are associated with C3-dependent extravascular haemolysis, it is important that a number of inhibitors of the proximal complement pathway are now in the offing and may further improve the life of patients with PNH.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Enbrel (etanercept) / Pfizer, Amgen, Cimzia (certolizumab pegol) / Astellas, UCB
Clinical, Review, Journal: Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road. (Pubmed Central) - Jun 16, 2021
Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier...Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
[VIRTUAL] DIFFUSE ALVEOLAR HEMORRHAGE AS A RARE COMPLICATION OF SEVERE ATYPICAL HEMOLYTIC UREMIC SYNDROME () - Jun 14, 2021 - Abstract #CSCTRMWAFMR2021CSCTR-MWAFMR_28;
Studies have additionally demonstrated that immediate rather than delayed treatment with eculizumab in aHUS patients leads to better outcomes. In Conclusion, aHUS with DAH is rare but it is important to include aHUS as a differential in pulmonaryrenal syndromes as timely diagnosis of aHUS and treatment with eculizumab is imperative to prevent morbidity and mortality.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Enrollment open: The Use of Eculizumab in HELLP Syndrome (clinicaltrials.gov) - Jun 11, 2021
P1, N=15, Recruiting,
In Conclusion, aHUS with DAH is rare but it is important to include aHUS as a differential in pulmonaryrenal syndromes as timely diagnosis of aHUS and treatment with eculizumab is imperative to prevent morbidity and mortality. Not yet recruiting --> Recruiting
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: De Novo Thrombotic Microangiopathy in Two Kidney Transplant Recipients From the Same Deceased Donor: A Case Series. (Pubmed Central) - Jun 11, 2021
Anti-complement blockade therapy with eculizumab is effective in some cases, but more studies are needed to identify appropriate candidates for therapy. We present two cases of de novo TMA occurring immediately in recipients from the same deceased donor and provoking the question of whether deceased donor related factors could represent risks for developing de novo TMA.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Ultomiris IV (ravulizumab IV) / Alexion Pharma
Journal: Novel therapeutics for paroxysmal nocturnal hemoglobinuria (Pubmed Central) - Jun 11, 2021
Although the administration interval has been extended and convenience has been greatly improved using the technique of recycling antibodies (ravulizumab and crovalimab), extravascular hemolysis has become another issue. Although attempts have been made to overcome this issue with proximal complement (C3, factor D, and factor B) inhibitors, the optimal therapeutic agent is expected to be selected after evaluating for not only efficacy and safety but also convenience.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Soliris (eculizumab) / Alexion Pharma
Biomarker, Clinical, Review, Journal: Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs. (Pubmed Central) - Jun 9, 2021
These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide...The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies).
- |||||||||| Soliris (eculizumab) / AstraZeneca, Ultomiris IV (ravulizumab-cwvz IV) / AstraZeneca
Enrollment open, Trial completion date, Trial primary completion date: Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab (clinicaltrials.gov) - Jun 8, 2021
P4, N=20, Recruiting,
The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies). Not yet recruiting --> Recruiting | Trial completion date: Feb 2022 --> Nov 2022 | Trial primary completion date: Feb 2022 --> Nov 2022
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Ultomiris IV (ravulizumab IV) / Alexion Pharma
Clinical, Review, Journal: Pregnancy with Paroxysmal Nocturnal Hemoglobinuria: A Case Series with Review of the Literature. (Pubmed Central) - Jun 5, 2021
The postpartum period was complicated in one case by portal vein thrombosis and was managed accordingly. In conclusion, pregnant females with PNH are at an increased risk for complications due to PNH, and thus experienced hematologists and obstetricians should be involved jointly in their care.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses. (Pubmed Central) - Jun 1, 2021
C5-blockade by eculizumab inhibited all the cytokines except G-CSF when induced by NPC...Finally, by using the TLR4 specific inhibitor Eritoran, we showed that TLR4 activation was the basis for the CD14 effect...Intriguingly, the inflammatory response was efficiently blocked by simultaneously targeting bottleneck molecules in the complement system (C5) and the TLR co-receptor CD14 with pharmaceutical inhibitors. We postulate that a combination of C5 and CD14 inhibition could have a great therapeutic potential to overcome the immunologic barrier in pig-to-human corneal xenotransplantation.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Characterising the original anti-C5 function-blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5. (Pubmed Central) - May 28, 2021
This antibody proved an invaluable tool to demonstrate complement involvement in mouse disease models and catalysed enthusiasm for anti-complement drug development, culminating in the anti-human C5 monoclonal antibody eculizumab, the most successful anti-complement drug to date, already in clinical use for several rare diseases...BB5.1 bound the C5 α-chain with high affinity and slow off-rate. BB5.1 complementarity determining regions were obtained and docking algorithms used to predict the likely binding interface on mouse C5.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Coversin SC (nomacopan SC) / Akari Therap
Journal: Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (Pubmed Central) - May 26, 2021
Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors...Stoichiometric C5 inhibitors failed to prevent conformational C5 activation, which explains the clinical phenomenon of residual C5 activity documented for different inhibitors of C5. The new insights into the mechanism of C3/C5 convertases provided here have important implications for the development and therapeutic use of complement inhibitors as well as the interpretation of former clinical and preclinical data.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Neuromyelitis Optica Spectrum Disorder (Pubmed Central) - May 26, 2021
Currently, there are additional options for therapy with biopharmaceutical agents such as eculizumab, satralizumab, rituximab, or inebilizumab to prevent relapse of the disease. These new options can clearly exceed or surpass the usual treatments and should be considered positively in aggressive cases of NMOSD.
- |||||||||| Aranesp (darbepoetin alfa) / Amgen, Kyowa Kirin, Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Delayed Severe Hemolytic Transfusion Reaction During Pregnancy in a Woman with β-Thalassemia Intermediate: Successful Outcome After Eculizumab Administration. (Pubmed Central) - May 20, 2021
Infusions of eculizumab (900 mg twice at a 7-day interval) followed by another course of intravenous immunoglobulins (2 g/kg/day for 5 days) and combined with repeated erythropoietin injections (darbepoetin alpha 300 µg/week) finally allowed biological and clinical improvement...CONCLUSIONS Eculizumab seems to be of benefit in DHTR associated with hyperhemolysis and should be used early in the treatment of this pathology. Despite premature birth, our case report showed an acceptable outcome for the infant when eculizumab treatment was used during pregnancy.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Review, Journal: Maintenance immunosuppression in myasthenia gravis, an update. (Pubmed Central) - May 15, 2021
The practical aspects of long-term immunosuppressive therapy in MG are critically reviewed in this article. Application of one or more of these specific therapies is guided based on known efficacy, adverse effect profile, particular disease subtype and severity, and patient co-morbidities.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Refractory vitiligo improving with Eculizumab. (Pubmed Central) - May 15, 2021
Application of one or more of these specific therapies is guided based on known efficacy, adverse effect profile, particular disease subtype and severity, and patient co-morbidities. No abstract available
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: The role of complement in kidney disease. (Pubmed Central) - May 15, 2021
This concept is illustrated by the prototypical complement-mediated renal disease atypical haemolytic uraemic syndrome (aHUS), which causes renal failure if untreated but when managed with the complement inhibitor eculizumab leaves the patient vulnerable to infection with encapsulated organisms...We review renal diseases in which complement over-activation is known to cause tissue injury; aHUS and C3 glomerulopathy. We also discuss the contribution of complement more widely to the pathophysiology of renal disease, and highlight the significance and side effects of anti-complement therapy relevant to the general physician.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Interferon-complement loop in transplant-associated thrombotic microangiopathy. (Pubmed Central) - May 15, 2021
The complement inhibitor eculizumab improves TA-TMA, but not all patients respond to therapy, prompting a search for additional targetable pathways of endothelial injury...We propose a model of an "interferon-complement loop" that can perpetuate endothelial injury and thrombotic microangiopathy. These findings open opportunities to study novel complement blockers and combined anti-complement and anti-interferon therapies in patients with TA-TMA and other microangiopathies like aHUS and lupus-associated TMAs.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Development of an anti-human complement C6 monoclonal antibody that inhibits the assembly of membrane attack complexes. (Pubmed Central) - May 15, 2021
Eculizumab, a monoclonal antibody (mAb) against complement component C5, is being used in the clinic to treat diseases in which MAC-mediated tissue damage is a primary cause...Finally, 1C9 significantly reduced human complement-mediated intravascular hemolysis in vivo in a mouse model. These results suggest that the anti-C6 mAb holds promise as a new therapeutic agent that selectively targets MAC for many complement-mediated pathological conditions.
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