NEJM Group’s Post

Our latest paper on the generation of Treg for adoptive transfer in type 1 diabetes is out in Immunology https://lnkd.in/dTQFhwpG

#FDA has given its approval for #inotuzumab #ozogamicin, (#Besponsa by Pfizer) for use in children aged 1 year and older suffering from a specific form of acute #lymphoblastic #leukemia (#ALL). This breakthrough therapy is designed for patients with relapsed or refractory CD22-positive B-cell precursor ALL that has aggressive nature and limited treatment options. A phase 2 study demonstrated a 42% complete remission rate, with a significant majority achieving minimal residual disease negativity. https://lnkd.in/diNJKurW

📃Scientific paper: Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial Abstract: Introduction Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. Methods In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n  = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo ( n  = 14) and BAM + ETE ( n  = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population ( N  = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. Results The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. Conclusion WBD in pediat... Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/LSoJ1

FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia On March 6, 2024, the Food and Drug Administration approved inotuzumab ozogamicin (Besponsa, Pfizer) for pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL). Full prescribing information for Besponsa will be posted here. Efficacy was evaluated in a multicenter, single-arm, open-label study in 53 pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor ALL. Two dose levels were evaluated--an initial dose of 1.4 mg/m2/cycle in 12 patients and 1.8 mg/m2/cycle in 41 patients. Premedications included methylprednisolone 1 mg/kg (maximum of 50 mg), an antipyretic, and an antihistamine. Patients received a median of 2 cycles of therapy (range: 1 to 4 cycles). #fda #approval #pediatric #leukemia https://lnkd.in/ghsyQ5Zc

New #AD monoclonal antibody therapies show promise, but eligibility is limited to older adults. Stay informed about the latest developments in #Alzheimerdisease treatment! #NeurologyUpdate Check out the details in this article: https://lnkd.in/emF_iHG7

Myasthenia gravis is an autoimmune disorder that affects the neuromuscular junction, leading to muscle weakness and fatigue. While traditional treatments such as acetylcholinesterase inhibitors and immunosuppressants like corticosteroids remain important, newer drugs have been developed to target specific aspects of the immune system or the neuromuscular junction itself. Here are some examples: Eculizumab (Soliris): Eculizumab is a monoclonal antibody that targets complement protein C5, inhibiting the complement cascade. It has been approved for the treatment of generalized myasthenia gravis in patients who are anti-acetylcholine receptor antibody positive. By inhibiting the complement system, eculizumab helps prevent the destruction of the neuromuscular junction. Ravulizumab (Ultomiris): Similar to eculizumab, ravulizumab is a monoclonal antibody that targets complement protein C5, providing sustained complement inhibition. It is also used for the treatment of generalized myasthenia gravis in patients who are anti-acetylcholine receptor antibody positive. Rozanolixizumab: This is another monoclonal antibody that targets the neonatal Fc receptor (FcRn), which plays a role in recycling immunoglobulins, including pathogenic autoantibodies. By blocking FcRn, rozanolixizumab reduces the levels of pathogenic antibodies, potentially providing benefits in myasthenia gravis. Fingolimod (Gilenya): Fingolimod is a sphingosine-1-phosphate receptor modulator that is approved for the treatment of multiple sclerosis. However, there is growing interest in its potential use for autoimmune disorders like myasthenia gravis. Fingolimod modulates lymphocyte trafficking and may have immunomodulatory effects that could be beneficial in MG. Zilucoplan: Zilucoplan is a subcutaneously administered macrocyclic peptide inhibitor of complement component 5 (C5) currently being investigated in clinical trials for the treatment of myasthenia gravis. It aims to provide targeted complement inhibition without the need for intravenous infusion. #drrashiddrugupdates

infection --> inflammatory cytokines --> EPO deficiency --> dysregulated immune system --> autoantibodies --> EPO resistance --> signs, symptoms and co-morbidities in LongCovid #LongCovid = continued Erythropoietin deficiency and/or EPO resistance https://lnkd.in/d7XKribK In the immune dysregulation, It is in particular CD8+ T cells that are "exhautsted" https://lnkd.in/diUDq4v2 STAT5 Is Critical To Maintain Effector CD8+ T Cell Responses https://lnkd.in/d5UyfHk5 STAT5 as a Key Protein of Erythropoietin Signalization https://lnkd.in/dWvygg-x (article only selected for the headline) "IgG autoantibodies might block or competitively inhibit EPOR ...": Erythropoietin Receptors and IgG Autoantibody ... Immuno-Related Pancytopenia https://lnkd.in/de6rjn3X Antibodies to Erythropoietin Are Associated with Erythropoietin Resistance in Hemodialysis ... https://lnkd.in/dppDpixt Additional articles: Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID https://lnkd.in/djrFAssj https://lnkd.in/dJ9YBZjC Pancytopenia and Profound Neutropenia as a Sequela of Severe SARS-CoV-2 Infection ... https://lnkd.in/d78PxPKs Association between Anti-Erythropoietin ... https://lnkd.in/dSSDQJkJ Akiko Iwasaki Harlan Krumholz Jeroen den Dunnen

➡️In type 1 diabetes, the immune system attacks beta cells (insulin-producing cells) in the pancreas. ➡️A monoclonal antibody (mAb)—teplizumab, which binds to immune T cells and reduces their interaction with beta cells—was approved for type 1 diabetes management by the FDA in 2022. Teplizumab delays the onset of stage 3 type-1 diabetes by about 2 years. ➡️In a study by researchers from Johns Hopkins, a mAb—mAb43—that binds to a small protein on beta cells was shown to mask beta cells from immune cell attack. ➡️In experiments on mice, it was observed that this approach has the potential to delay type-1 diabetes onset for as long as it's administered. ➡️Researchers are now working on developing a humanized version of mAb43 that can be tested in clinical trials.

Fast Track Designation - Johnson & Johnson's nipocalimab Last week, the FDA granted fast track status for J&J’s investigational monoclonal antibody (mAb) nipocalimab in another rare blood disorder called fetal and neonatal alloimmune thrombocytopenia (FNAIT). According to the company, this is the only investigational therapy currently in clinical development targeting the above indication. This designation comes following a phase 2 PoC study completed within HDFN, a disease with a similar mechanism to FNAIT. Read more below: #fasttrackdesignation #womenshealth #johnsonandjohnson #nipocalimab https://lnkd.in/eZxiaEfU

“Plasma ET-1 levels are elevated in patients with type 1 or type 2 diabetes [18–20]. A significant correlation has been observed between plasma ET-1 levels and diabetic complications. ET-1 levels are higher in patients with microalbuminuria, elevated glycosylated hemoglobin (HbA1c) concentrations retinopathy.” Would be interesting to explore several bridging biomarkers.