tesidolumab (LFG316) / Novartis - LARVOL DELTA

Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig-to-Rhesus Monkey Renal Xenografts. (PubMed, Xenotransplantation) - "It may be reasonable to evaluate an iscalimab-based immunosuppressive regimen in clinical renal xenotransplantation."

Journal • Preclinical • Transplantation • CD40LG • CD55

Complement inhibition in PHN: from biology to therapy (ISLH 2024) - "The anti-C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life-long intravenous fortnightly drug...Ravulizumab, a longer half-life anti-C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti-C5 concentrations. More recently, several other anti-C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti-C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti-factor B) and danicopan (anti-factor D)...Additionally, both anti-C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review,..."

Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy. (PubMed, Int J Lab Hematol) - "The anti-C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life-long intravenous fortnightly drug...Ravulizumab, a longer half-life anti-C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti-C5 concentrations. More recently, several other anti-C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti-C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti-factor B) and danicopan (anti-factor D)...Additionally, both anti-C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review,..."

Journal • Review • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

EFFICACY AND SAFETY OF SWITCHING TO IPTACOPAN (IPTA) MONOTHERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) TREATED WITH THE ANTI-C5 MONOCLONAL ANTIBODY (MAB) TESIDOLUMAB (TESI) (EHA 2023) - P2, P3 | "Background: The anti-C5 mAbs eculizumab (ECU) and ravulizumab (RAV) are standard treatment for PNH patients (pts). TESI, a mAb targeting C5 in the terminal complement pathway, led to early, sustained LDH decreases in PNH pts with or without C5 variants, which were maintained when switching to IPTA, an inhibitor of factor B in the alternative pathway. TESI was effective in improving Hb and PNH type III RBCs, with further increases in Hb seenwhen switching to IPTA. Improvements in reticulocytes and bilirubin were seen when pts switched to IPTA, suggesting that IPTA controlled both IVH and EVH."

Clinical • Monotherapy • Anemia • Complement-mediated Rare Disorders • Dermatology • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Pain • Paroxysmal Nocturnal Hemoglobinuria • Pruritus • Rare Diseases • Renal Calculi • Renal Disease • CFB

HOW WE (WILL) TREAT PNH? (EHOC 2022) - "Crovalimab, binding on the single missense C5 heterozygous mutation is injected s.c. monthly; two large phase III trials are ongoing as add on- and mono-therapy. Others, such as Pozelimab, injected subcutaneously on a weekly basis after an initial IV loading dose or Tesidolumab are still under current investigation...In a recent phase III trial, pegcetacoplan showed superiority to eculizumab in hemoglobin change from baseline and is now approved by the FDA for patients with PNH who are either treatmentnaive or switching from antiC5 monoclonal antibodies. Danicopan is an oral first- inclass factor D complement alternative pathway inhibitor and decreased significantly transfusion requirement, as shown in a phase II trial (phase III ongoing). BCX9930, another FD inhibitor in early development is given orally and demonstrated initial clinical efficacy both as addon therapy in patients with inadequate response to eculizumab as well as in monotherapy in treatmentnaive..."

Anemia • Bone Marrow Transplantation • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation • CFB

Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): two phase 3 randomised, controlled trials. (PubMed, Lancet Gastroenterol Hepatol) - P3 | "Etrolizumab was superior to placebo for induction of remission in HIBISCUS I, but not in HIBISCUS II. Etrolizumab was well tolerated in both studies."

Clinical • Journal • P3 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis

Physiologically-Based Pharmacokinetic Modelling of Immunoglobulin and Antibody Co-Administration in Primary Human Immunodeficiency Patients. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Model predictions were within 1.5-fold of observed values for 7E3 plus IVIG and tesidolumab plus IVIG as well as for JSP191 administered alone. Based on our simulations, IVIG doses ≥ 500 mg exceeded the 80-125 percent no-effect boundaries. IVIG treatment with monoclonal antibodies in patients with PI may result in a clinically significant interaction, depending on the IVIG dose administered and the exposure response relationship for the specific monoclonal antibody."

Journal • PK/PD data • Acute Myelogenous Leukemia • Chronic Kidney Disease • Genetic Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Immunology • Leukemia • Myelodysplastic Syndrome • Nephrology • Oncology • Pediatrics • Primary Immunodeficiency • Renal Disease • CD61 • KIT

Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment. (PubMed, Pol Arch Intern Med) - "Determinants of modern treatment, such as strategies (complement C5 inhibitors vs hematopoietic stem cell [HSC] allotransplantation), the safety and efficacy of treatment with eculizumab or ravulizumab, policy of initiation and monitoring of treatment, the criteria for response to treatment and final outcomes of treatment are described. Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted."

Journal • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation

Tesidolumab (LFG316) for treatment of C5-variant patients with paroxysmal nocturnal hemoglobinuria. (PubMed, Haematologica) - "Not available."

Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Retracted: Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue. (PubMed, Med Sci Monit) - "2014 Nov 4;20: 2157-64...Med Sci Monit, 2014; 20: 2157-2164. DOI: 10.12659/MSM.890654."

Journal • Musculoskeletal Diseases

"What is new and exciting for ER+ MBC? Dr. Nancy Lin, MD @nlinmd @DanaFarber explains. @ourmbclife special series Road to a Cure #MBC #bcsm #ourmbclife #thisismbc #moreforstageiv 8:21 PM · Nov 4, 2021·Canva 4 Retweets 1 Quote Tweet 15 Likes Relevant people" (@ourmbclife)

Breast Cancer • Solid Tumor

"My 7 year old grandson received his vaccination and large certificate on Thursday Nov.4." (@jlm815_mcgee)

Clinical

"#ASH21 Abstracts online Nov 4, 2021 --> https://t.co/3x032Uai5W @symplur @ASH_hematology" (@mtmdphd)

Hematological Disorders

"$BLUE on Nov 4 completed the spin-off of its oncology business, 2seventy bio, Inc. 2seventy to begin trading on the Nasdaq eff Nov 5. $TSVT" (@BioStocks)

Oncology

"Symptom Intervention Committee co chaired by @KathrynRuddyMD and @maryam_lustberg Nov 4 530 pm EST #survonc #supponc @ALLIANCE_org #NCORP @NCISymptomMgmt @theNCI cc @YaleCancer @MayoCancerCare" (@maryam_lustberg)

Oncology

"Join us @NeuPsig on Nov 4 for a series of exciting data blitzes from young investigators #LindaSangalli, @PT_DPrescribing and @JFundaun @PainResForum @IASPpain" (@S_Haroutounian)

Pain

"$ATNM $170M MCAP major catalysts next week. 1) 3rd QTR earnings 2) #ASH21 3-5 abstracts release Nov 4 3) #SITC21 2 abstracts release Nov 9 $ISEE $PDSB $PAVM $CLDX $MGNX $HALO $SGMO $SPRT $CLOV $AMC $GME $CYTK $SLS $INO $ALXO $IMAB $tril $bmy $tgtx $BNTX $DVAX $EXEL $CRTX" (@ej23ny)

Oncology

Efficacy and safety of mitoxantrone hydrochloride liposome injection in Chinese patients with advanced breast cancer: a randomized, open-label, active-controlled, single-center, phase II clinical trial. (PubMed, Invest New Drugs) - P2 | "This trial aimed to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection (Lipo-MIT) in advanced breast cancer (ABC). This study is registered with ClinicalTrials.gov (No. NCT02596373) on Nov 4, 2015."

Clinical • Journal • P2 data • Breast Cancer • Cardiovascular • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor

[VIRTUAL] Tisagenlecleucel (Tisa) for relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL): B2001X study focusing on prior exposure to blinatumomab (BLINA) and inotuzumab (INO). (ASCO 2020) - P2, P3 | " As of Nov 4, 2019, 73 pts were enrolled; 67 received tisa. Outcomes in B2001X remain consistent with ELIANA. In pts with prior BLINA or INO as BT, a trend toward suboptimal outcomes was observed but should be interpreted with caution due to small n, short FU and potential confounding factors. Research Funding: Novartis"

Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology

Azithromycin for the prevention of rehospitalisation and death among Kenyan children being discharged from hospital: a double-blind, placebo-controlled, randomised controlled trial. (PubMed, Lancet Glob Health) - P4 | "We did not observe a significant benefit of a 5-day course of azithromycin delivered to children younger than 5 years at hospital discharge despite the overall high risk of mortality and rehospitalisation. These findings highlight the need for more research into mechanisms and interventions for prevention of morbidity and mortality in the post-discharge period."

Clinical • Journal • Mood Disorders

[VIRTUAL] Bianca: Phase II, single-arm, global trial to determine efficacy and safety of tisagenlecleucel in pediatric/young adult (YA) patients (Pts) with relapsed/refractory B-cell non‑Hodgkin lymphoma (R/R B-NHL). (ASCO 2020) - P2 | " As of Nov 4, 2019, 8 pts were enrolled, of whom 4 had large B-cell lymphoma (LBCL), 3 Burkitt lymphoma (BL), and 1 gray zone lymphoma (GZL) (Table). Pediatric/YA pts with r/r B-NHL (including BL) were successfully infused with tisagenlecleucel in the BIANCA trial with a manageable safety profile. Apheresis/manufacturing were feasible in this cohort of rapidly progressing disorders. Tisagenlecleucel was shown to expand in vivo."

Clinical • P2 data • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics

[VIRTUAL] Difference is Risk Factors and Clinical Outcomes in Pediatric Patients with Deep Venous Thrombosis as Compared to Pulmonary Embolism (ISTH 2021) - "Methods : In this retrospective single-center cohort study, we included consecutive patients < 21 years with radiologically confirmed PE or DVT between Jan 1, 2001, and Nov 4, 2020...Conclusions : Pediatric PE patients have unique risk factors and outcomes as compared to those with DVT. This finding needs to be confirmed in larger studies."

Clinical • Clinical data • Cardiovascular • Hematological Disorders • Immunology • Inflammatory Arthritis • Obesity • Pediatrics • Pulmonary Embolism • Respiratory Diseases • Systemic Lupus Erythematosus • Venous Thromboembolism

[VIRTUAL] Difference is Risk Factors and Clinical Outcomes in Pediatric Patients with Deep Venous Thrombosis as Compared to Pulmonary Embolism (ISTH 2021) - "Methods : In this retrospective single-center cohort study, we included consecutive patients < 21 years with radiologically confirmed PE or DVT between Jan 1, 2001, and Nov 4, 2020...Conclusions : Pediatric PE patients have unique risk factors and outcomes as compared to those with DVT. This finding needs to be confirmed in larger studies."

Clinical • Clinical data • Cardiovascular • Hematological Disorders • Immunology • Inflammatory Arthritis • Obesity • Pediatrics • Pulmonary Embolism • Respiratory Diseases • Systemic Lupus Erythematosus • Venous Thromboembolism

Anti-C5 Antibody Tesidolumab Reduces Early Antibody Mediated Rejection And Prolongs Survival In Renal Xenotransplantation. (PubMed, Ann Surg) - "Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days."

Journal • Antibody-mediated Rejection • Immune Modulation • Inflammation • Transplantation • CD40LG