MHU650 / Novartis - LARVOL DELTA

Phase III COMMODORE 2 and 1 Trials: Characterization of Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Treated with Crovalimab or Eculizumab (ASH 2024) - P3 | "Introduction Crovalimab (crova; PiaSky®), a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) maintenance dosing (weight-based tiered regimen) every 4 weeks (Q4W) , was assessed vs eculizumab (ecu) in the global, randomized, Phase III COMMODORE 2 and 1 trials (NCT04434092; NCT04432584; primary analysis clinical cutoff date [CCOD] : Nov 16, 2022). A similar trend was seen in the ecu arms. Overall, updated CCOD results show that BTH was infrequent with crova and further support the favorable benefit–risk profile of crova in both C5i-naive and C5i-experienced pts with PNH."

Clinical • P3 data • Anemia • Complement-mediated Rare Disorders • Erectile Dysfunction • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Disease • Rare Diseases • PIAS4

Individualized Flow-Controlled versus Pressure-Controlled Ventilation in Cardiac Surgery: A Randomized Controlled Trial. (PubMed, Anesthesiology) - "FCV did not reduce plasmatic IL-8 levels at the predefined timepoint six hours after cardiopulmonary bypass. However, the reduction of mechanical power during individualized FCV application and the findings of the explorative secondary study outcomes justify future trials."

Journal • Cardiovascular • Infectious Disease • Pneumonia • Respiratory Diseases • CXCL8

Cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): a prospective, open-label, multicentre, non-inferiority, randomised clinical trial. (PubMed, Lancet) - P=N/A | "Cefazolin constitutes an alternative to cloxacillin for the treatment of MSSA bacteraemia, offering non-inferior clinical efficacy and potentially enhanced tolerability."

Head-to-Head • Journal • Acute Kidney Injury • Cardiovascular • Infectious Disease • Nephrology • Renal Disease

Does Tranexamic Acid (TXA) Influence Postoperative Wound Healing in Orthognathic Surgery? (AAOMS 2025) - "Abstract: Statement of the Problem:Tranexamic acid (TXA) is an antifibrinolytic agent utilized in surgical procedures and hemostatic disorders to prevent the deterioration of blood clots and aid hemostasis. TXA did not demonstrate any significant advantage nor detriment to intraoral wound healing following orthognathic surgery. BSSO incisions appear to be more prone to wound healing complications.References: 1. Xu JW, Qiang H, Li TL, Wang Y, Wei XX, Li F. Efficacy of topical vs intravenous tranexamic acid in reducing blood loss and promoting wound healing in bone surgery: A systematic review and meta-analysis."

Surgery • Infectious Disease • Orthopedics • Thrombosis

Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. (PubMed, Lancet) - P3 | "Adagrasib demonstrated a statistically significant improvement in progression-free survival over docetaxel in patients with previously treated KRASG12C-mutated NSCLC, without new safety signals."

Clinical • IO biomarker • Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Immersive virtual reality-assisted therapy targeting persistent auditory verbal hallucinations in patients diagnosed with schizophrenia spectrum disorders in Denmark: the Challenge assessor-masked, randomised clinical trial. (PubMed, Lancet Psychiatry) - P=N/A | "Challenge-VRT showed short-term efficacy in reducing the severity of auditory verbal hallucinations in patients with schizophrenia, and the findings support further development and evaluation of immersive virtual reality-based therapies in this population."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan. (PubMed, Lancet) - "iCEPS transplantation for LSCD was found to be safe throughout the study period. A larger clinical trial is planned to further investigate the efficacy of the procedure."

Journal • P1 data • Surgery • Immunology • Oncology • Ophthalmology • Transplantation

Measuring the Effectiveness of Three Instructional Interventions for Supporting Laypeople Addressing Prehospital Hemorrhage (SLAPS): A Randomized Clinical Trial (ACS-CLINCON 2024) - P=N/A | " From Jan 23, 2023-Nov 16, 2023, 166 participants were enrolled, with 8 lost-to-follow-up(5.06%)... POC instruction demonstrated comparative efficacy to in-person training longitudinally, suggesting an alternative for prehospital rapid compressible hemorrhage control in LMICs. POC materials can enhance global health education, empowering bystanders in resource-limited settings to prevent trauma-related morbidity and mortality."

Clinical • Hematological Disorders

Rethinking MASH (AASLD 2024) - "This symposium also explores the challenges of a holistic approach to MASH patients with competing comorbidities and multi-organ involvement as well as novel approaches involving lifestyle interventions. For more information and to register, visit: https://healthpromatch.com/cme-event-nov-16/ Understand new treatments available for MASH and analyze current evidence-base for non-invasive tests (NITs) in the diagnosis, monitoring and prognostication of patients with MASH Reflect on how new treatments, NITs and PROMS in MASH can be incorporated into manageable patient pathways in primary and secondary care Reflect on how to manage competing risks in patients with MASH Consider the impact of MASH on population health and consider how non-pharmaceutical/ lifestyle interventions can be incorporated into patient pathways"

Metabolic Dysfunction-Associated Steatohepatitis

Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial. (PubMed, Lancet Rheumatol) - P2 | "These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR."

Journal • P2 data • Immunology • Osteoarthritis • Pain • Rheumatology

Phase II Trial of Ubamatamab in MUC16-Expressing SMARCB1-Deficient Renal Medullary Carcinoma and Epithelioid Sarcoma (KCRS 2024) - "As proof of concept, a 20-year-old patient with metastatic SMARCB1-negative ES expressing high levels of serum CA125 achieved a durable (12+ months) partial response to ubamatamab after progressing on multiple prior therapies, including EZH2 inhibition with tazemetostat as well as antiPD1/CTLA4 immune checkpoint inhibition with nivolumab plus ipilimumab...Patients with disease progression on ubamatamab monotherapy during Stage I can proceed to stage II, which will evaluate the combination of ubamatamab with cemiplimab combination...Mucin 16 (cancer antigen 125) Expression in Epithelioid Sarcoma leads to Single-Patient Study with Bispecific T-Cell Engager Ubamatamab (Mucin16xCD3): A Bench-ToBedside Experience. Connective Tissue Oncology Society, Nov 16–19, 2022, Vancouver, Canada."

IO biomarker • P2 data • Cardiovascular • Kidney Medullary Carcinoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Respiratory Diseases • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MUC16 • SMARCB1

Altitudinal distribution and body condition of migratory fish juveniles Megaleporinus obtusidens (Valenciennes) and Salminus brasiliensis (Cuvier) in the main channel of the Uruguay River, Southern Brazil. (PubMed, Braz J Biol) - "The nets remained in the water for 10-12 hours per night or day for 10 days during each field trip (NOV-15, MAR-16, NOV-16, and MAR-17)...Altitude gradient and water level were factors that may affect the juvenile distribution and body condition of these species, respectively, in the Uruguay River. Therefore, this information can be used in hydropower generation policies to conserve migratory fish populations in the Uruguay River Basin."

Journal

Genetic polymorphisms associated with UTI in children and adults: a systematic review and meta-analysis. (PubMed, Am J Obstet Gynecol) - "This systematic review provides a current synthesis of the known genetic architecture of UTI in childhood and adulthood, and should provide important information for researchers analysing future genetic association studies. Although, overall, the credibility of pooled associations was weak, the consistency of findings for rs2234671 SNP of CXCR1 in both populations suggest a key role in the UTI pathogenesis."

Journal • Retrospective data • Review • Infectious Disease • Nephrology • Pediatrics • CXCL8 • CXCR1 • TLR4

Durability and cross-reactive immune memory to SARS-CoV-2 in individuals 2 years after recovery from COVID-19: a longitudinal cohort study. (PubMed, Lancet Microbe) - "This study improves the understanding of the duration of SARS-CoV-2-specific immunity without boosting, which has implications for the design of vaccination regimens and programmes. Our data suggest that memory T-cell responses primed by initial viral infection remain highly cross-reactive after 2 years. With the increasing emergence of variants, effective vaccines should be introduced to boost neutralising antibody and overall T-cell responses to newly emerged SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study. (PubMed, Lancet Respir Med) - "Most long COVID symptoms at 3 years were mild to moderate, with lung function recovering to levels of matched controls. Survivors with long COVID had a higher proportion of participants with re-infection and newly occurring or worse symptoms 3 months after omicron infection than those without long COVID. Re-infection had increased symptom occurrence but not increased reduced daily activity. Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research."

Journal • Bronchiectasis • CNS Disorders • Depression • Infectious Disease • Mood Disorders • Novel Coronavirus Disease • Pneumonia • Psychiatry • Pulmonary Disease • Respiratory Diseases

W1-RCP20 Who is Paying for Radiology Education? (Sponsored by the American Association for Women in Radiology) (RSNA 2023) - "2021 Nov 16;9(11):1557...Epub 2021 Jun 25. PMID: 34176728."

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Extensive transmission of SARS-CoV-2 BQ.1 variant in a population with high levels of hybrid immunity (ASTMH 2023) - "As part of a long-term cohort study, we conducted a prevalence survey during the BQ.1* wave between Nov 16 th and Dec 22 nd , 2022 in Salvador, Brazil...The lower disease severity associated with BQ.1*, as compared with prior Omicron variants, contributed to significant under-reporting of infection. As observed for BQ.1* in this study, hybrid immunity may provide weak protection against future SARS-Co V-2 variants and may not prevent widespread transmission after their introduction."

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The phase iii randomized, multicenter commodore 1 trial: comparison of crovalimab vs eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH) (DGHO 2023) - P3 | " The clinical data cutoff was Nov 16, 2022. The safety profile of crova in C5i-experienced patients with PNH is consistent with that in C5i-naive patients, except for transient, self-limiting T3H events unique to patients switching between crova and ecu. The COMMODORE 1 data comparing crova vs ecu in C5i-experienced patients support the favorable benefit–risk profile of crova, including allowing for subcutaneous administration every 4 weeks with the option to self-administer."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

The phase iii, randomized, multicenter commodore 2 trial: results from the study of crovalimab vs eculizumab in paroxysmal nocturnal hemoglobinuria (PNH) patients naive to complement inhibitors (DGHO 2023) - P3 | " At primary analysis (clinical data cutoff on Nov 16, 2022), 204 patients were randomized (crova: n=135; ecu: n=69). The COMMODORE 2 study demonstrated that crova was non-inferior to ecu in both co-primary efficacy endpoints and had a comparable safety profile. These data highlight the overall favorable benefit–risk profile of crova, including allowing for subcutaneous administration every 4 weeks with the option to self-administer."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual, and other men who have sex with men in England: a mathematical modelling study. (PubMed, Lancet Infect Dis) - "The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks."

Journal • Infectious Disease

Real-world clinical outcomes and treatment patterns among patients with triple-class exposed multiple myeloma: an analysis using the Connect® Multiple Myeloma Disease Registry (IMW 2023) - P=N/A | "The current study was conducted in multiple myeloma patients enrolled in the Connect MM® registry who became TCE from Nov 16, 2015 to Dec 31, 2020 and who had received an index treatment post-TCE status...Index treatments were varied (101 monotherapy or combination regimens in total) and carfilzomib/dexamethasone (DEX) (7.4%) and daratumumab/pomalidomide/DEX (7.0%) were the most commonly used treatments. In the real-world prospective Connect MM Disease Registry, patients with TCE MM had poor response and survival outcomes, with TCE occurring at a median of 3 prior lines of therapy. This study highlights the need for more efficacious and accessible novel treatments for patients with TCE MM, irrespective of number of lines of prior therapy."

Clinical • Clinical data • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial. (PubMed, Lancet Haematol) - P3 | "These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience."

Journal • P3 data • Hematological Disorders • Hemophilia • Rare Diseases

PHASE 2 WAVELINE-004 STUDY: ZILOVERTAMAB VEDOTIN (MK-2140) IN RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) (EHA 2023) - P2 | " At the data cutoff (Nov 16, 2022), 40 pts had been enrolled and had received ≥1 dose of zilovertamab vedotin; 23 (58%) pts had discontinued treatmentand 17 (43%) were ongoing.The median age was 68.0 years, 29 pts (73%) were male, 37 pts (93%) had an ECOG PS of 0 or 1,and 24 pts (60%) had received ≥3 prior lines of therapy. Theseearly results from waveLINE-004 show that zilovertamab vedotin had clinically meaningful antitumor activity and a manageablesafety profilethat was consistent with other monomethyl auristatin E–containing agents in pts with R/R DLBCL who had progressed after or wereineligiblefor ASCTand CAR-Tcell therapy."

P2 data • Alopecia • Anemia • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Metabolic Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Transplantation • ROR1

PHASE III RANDOMIZED, MULTICENTER, OPEN-LABEL COMMODORE 1 TRIAL: COMPARISON OF CROVALIMAB VS ECULIZUMAB IN COMPLEMENT INHIBITOR-EXPERIENCED PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) (EHA 2023) - P3 | " The clinical data cutoff was Nov 16, 2022. The safety profile of crova in C5i-experienced pts with PNH is consistent with that in C5i-naive pts, except for transient, self-limiting T3H events unique to pts switching between crova and ecu. The COMMODORE 1 data comparing crova vs ecu in C5i-experienced pts support the favorable benefit–risk profile of crova, including allowing for SC administration with the option to self-administer. Phase III, Paroxysmal nocturnal hemoglobinuria (PNH), Complement, Randomized"

Clinical • P3 data • Complement-mediated Rare Disorders • Dermatology • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Meningococcal Infections • Musculoskeletal Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Urticaria • Vasculitis

THE PHASE III, RANDOMIZED COMMODORE 2 TRIAL: RESULTS FROM A MULTICENTER STUDY OF CROVALIMAB VS ECULIZUMAB IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) PATIENTS NAIVE TO COMPLEMENT INHIBITORS (EHA 2023) - P3 | " At primary analysis (clinical cutoff of Nov 16, 2022), 204 pts were randomized (135 to crova; 69 to ecu). The COMMODORE 2 study demonstrated that crova was non-inferior to ecu in both co-primary efficacy endpoints and had a comparable safety profile. These data highlight the overall favorable benefit–risk profile of crova, including allowing for SC administration with the option to self-administer. Randomized, Complement, Paroxysmal nocturnal hemoglobinuria (PNH), Phase III"

Clinical • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Ischemic stroke • Meningococcal Infections • Myocardial Infarction • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases