Camilla Fedi’s Post

Clinical Trails Updates: Calliditas Therapeutics Releases Positive Phase III Results for Nefecon in Primary IgA #Nephropathy Clinical Trial Primary IgA nephropathy, also known as IgAN or Berger's disease, is a prevalent #autoimmune #kidney condition affecting approximately 10% of kidney biopsy samples. It is characterized by the accumulation of IgA antibodies in the kidneys, resulting in kidney dysfunction and the presence of protein and blood in the urine. Unfortunately, around 50% of individuals with this condition progress to end-stage kidney disease, necessitating dialysis or a kidney transplant. Excitingly, Calliditas' groundbreaking drug Nefecon has yielded highly positive results in its recently published Phase III #clinicaltrial. Here's a brief overview: - Nefecon demonstrated significant kidney protection compared to a placebo, effectively slowing kidney function decline and potentially delaying the need for dialysis or transplantation. - The study underscored the vital role of the gut immune system in IgAN and highlighted Nefecon's capacity to address the origins of the disease. - Over the two-year study period, Nefecon showcased both statistically and clinically meaningful benefits for estimated glomerular filtration rate (eGFR). - Patients receiving Nefecon maintained consistent proteinuria (protein-in-urine) reduction of over 30% for an entire year. - Nefecon exhibited favorable tolerability, resulting in minimal discontinuations. In conclusion, these promising results inspire strong hope for #fda approval and the potential introduction of a groundbreaking therapy for individuals living with nephropathy. #medicalaffairs #clinicaldevelopment #medicalcareers #medicalprofessional https://lnkd.in/ezi5x-Nf

Great news for hypertensive Patients :- A new study shows new anti-hypertensive Medication ,, zilebesiran “” which target hepatic angiotensinogen synthesis with the RNA interference and significantly reduce blood pressure in adults with light to moderate Hypertension. Patients with Hypertension can get subcutaneous zilebesiran Injection every 3 or 6 Months instead taking oral medication daily. Single subcutaneous doses of zilebesiran significantly lower blood pressure for up to 6 months, suggesting potential for use as an effective antihypertensive with quarterly or biannual dosing. Angiotensinogen is the most upstream precursor of the renin–angiotensin–aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic. The Study is randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries. Screening initiation occurred in July 2021 and the last patient visit of the 6-month study occurred in June 2023. Adults with mild to moderate hypertension, defined as daytime mean ambulatory systolic BP (SBP) of 135 to 160 mm Hg following antihypertensive washout, were randomized. Interventions Randomization to 1 of 4 subcutaneous zilebesiran regimens (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo (once every 3 months) for 6 months. In adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3.

Calliditas Therapeutics has announced publication of its NefIgArd trial in The Lancet. The phase 3 study concerns the use of Nefecon among adult patients with primary IgA nephropathy (IgAN). The clinical trial met the primary endpoint – estimated glomerular filtration rate (eGFR) – with Nefecon duly showing a considerable kidney protective impact versus the placebo. The analysis also demonstrated that Nefecon has a clinically relevant and statistically significant benefit compared to placebo, in eGFR, over nine-months of using Nefecon and 15-months of follow-up treatment. The decrease in urine protein/creatinine ratio (UPCR) observed with Nefecon treatment was resilient, indicating a long-lasting treatment effect during the 15-month follow-up treatment period. Patients treated with Nefecon sustained a greater than 30% proteinuria reduction from the end of the nine-month treatment and throughout the duration of the follow-up period, with a reduction in UPCR of over 50% observed at one year. Ultimately, Nefecon was well tolerated, with the majority of adverse events either mild or moderate, while objective measures of mean weight and blood pressure showed non-clinically relevant changes. Renée Aguiar-Lucander, Chief Executive Officer at Calliditas, reflected: “We are thrilled to see the NefIgArd Phase 3 data published in The Lancet, highlighting these important results for the IgAN patient community.” She added: “The established long-term eGFR benefit reflects Nefecon’s ability to slow kidney function decline by targeting the origin of the disease and providing a differentiated and disease-modifying treatment alternative.” Read more: https://lnkd.in/gbVFTh8v

Daratumumab is increasingly incorporated into the standard treatment regimens for patients with plasma cell dyscrasias in Asia, especially with cost-containment measures implemented by various regional health authorities. This analysis aimed to study daratumumab’s tolerability amongst Asian patients. This is a retrospective medical records review of patients who received daratumumab between November 2016 and August 2021 as part of routine clinical care. Sixty-two patients were included in the study: 62.9% had renal impairment, and 27.4% had creatinine clearance (CrCl) <30ml/min. Forty-five patients (72.6%) received daratumumab combination therapy, with a median 1 line of prior therapy. The median duration of follow-up was 12.4 months, and the median duration patients were on treatment with daratumumab was 12.3 months. Twenty-one of 62 (33.9%) patients experienced infusion-related reactions (IRRs) after the first dose of intravenous daratumumab. Seven developed mostly grades 1 and 2 respiratory events, and 14 showed grades 1 and 2 non-respiratory IRRs. Only one patient experienced a grade 1 IRR with the second infusion, with none developing any IRRs in the third or subsequent infusions. Eight (12.9%) patients were affected by hematological adverse events (AEs), mostly grades 2 and 3, with one experiencing grade-4 neutropenia without sepsis. Six (9.7%) patients experienced non-hematological AEs, the commonest being pneumonia and other infections, with one developing Nocardia pneumonia (grade 4) 14 months after the initiation of daratumumab. In conclusion, daratumumab is tolerable amongst Asian patients, including the elderly, and patients with severe renal impairment and chronic lung diseases. https://lnkd.in/gFivnAM9

The FDA recently granted accelerated approval to epcoritimab in R/R follicular lymphoma after two or more lines of systemic therapy.  It's unlikely to see much use in this indication, since few patients actually reach the third line of treatment, but it's good to have an option in this space.  More interesting is the dosing of epcoritimab which was approved, which was given as a three-dose step-up instead of a two-dose step-up.  Investigators compared a two-dose step-up to a three-dose step up in their phase I/II trial, and found similar response rates.  The rates of grade 1 CRS were similar (40% vs 40%), but grade 2 (9% vs 25%) and grade 3 (0% vs 2%) CRS was lower in the three-dose step up.  In addition, the three-dose step-up had no ICANS while the two-dose step-up had 6% ICANS.  Does this mean we could use this step-up dosing in DLBCL?  It's difficult to say, as these are biologically distinct diseases, and it is possible that a faster ramp-up is important for DLBCL.  As the bispecific field evolves, we will probably see changes to the step-up dosing schedules, probably with smaller and more frequent step-up doses, to enable it to be given outpatient.   However, once we decide on an "optimal" step-up dosing strategy, it is important to validate it in all disease states. #follicularlymphoma #dlbcl #epkinly https://lnkd.in/eDq5FN8r

argenx Data Highlight Evidence that VYVGART and VYVGART Hytrulo Drive Transformative Outcomes for Patients with Debilitating Autoimmune Disease :- •#ADHERE data show VYVGART®Hytrulo has potential to be first advancement for CIDP patients in 30 years. •Real-world data demonstrate gMG patients able to significantly reduce steroid use over first six months of initiating VYVGART® treatment. •ADHERE Plenary Session (PL5) Highlights Rapid, Deep and Clinically Meaningful, and Durable Functional Improvementsin CIDP. •#Evidence of rapid onset and maintenance of clinical response:-Results across both Stage A and B indicate IgG autoantibodies play a significant role in mediating the underlying biology of CIDP. •#Deep and clinically meaningful functional improvements :-81% of VYVGART Hytrulo-treated patients demonstrated ≥1 point improvement on the aINCAT as compared to baseline Stage A scores in ADHERE, which includes 42% of patients with ≥2 point improvement, 28% with ≥3 point improvement, and 12% with ≥4 point improvement. •#Clinical benefit demonstrated regardless of prior CIDP treatment:-Clinical benefit was seen across all patient subtypes, including those who had previously received corticosteroids, intravenous or subcutaneous immunoglobulin, or were on no treatment prior to study entry. •#High rate of treatment continuation:-99% of eligible patients continued to the ADHERE-Plus open-label extension study. •#FDA decision on CIDP sBLA expected by June 21, 2024:- Data from the ADHERE trial were submitted to the U.S. Food and Drug Administration (FDA) as part of a supplemental Biologics License Application (sBLA) for VYVGART Hytrulo for the treatment of CIDP. The application was accepted for Priority Review in February 2024 and has been granted a PDUFA target action date of June 21, 2024.

CHAPLE syndrome: Veopoz® is the first FDA-approved drug Veopoz®(pozelimab-bbfg) receives FDA Approval as the First Treatment for Children and Adults with CHAPLE Disease (by Regeneron Pharmaceuticals). Although the proof of concept of complement C5 (component 5) inhibition in CHAPLE disease was already shown with eculizumab (approved by the FDA in 2007, used to treat a number of autoimmune conditions), the prospective design of this study enabled the approval of pozelimab (Veopoz®) by the FDA. An advantage of pozelimab over eculizumab is the subcutaneous administration, providing an important benefit for quality of life compared with intravenous administration in hospital. Additionally, pozelimab appears to be well tolerated, with no severe adverse events associated with the treatment. CHAPLE - acronym for "Complement Hyperactivation, Angiopathic thrombosis, and Protein-Losing Enteropathy" - is a rare genetic disease characterized by CD55 deficiency, with abdominal pain, diarrhea, vomiting, primary intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption, leading to anemia and growth delay. Bowel inflammation and recurrent infections associated with hypogammaglobulinemia may also be observed. CHAPLE is one of the 8,000 rare diseases that affect more than 350 million individuals worldwide. Of these, about 80% of these diseases have a genetic basis. And Chaple is one of them. #Chaple #RaraDisease #Pozelimab #Veopoz The Lancet (Published online January 23, 2024) https://lnkd.in/d2xmHxEN https://lnkd.in/djMJJBWz

📃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

Recommendations Caplacizumab should be initiated on confirmation of acute iTTP and for up to 30 days following completion of PEX. In patients who remain severely ADAMTS13 deficient (<20 IU/dL) caplacizumab therapy may be continued. (1A) Intravenous daily methylprednisolone (e.g. 1 g/day for three consecutive days—adult dose) or high-dose oral prednisolone (e.g. 1 mg/kg/day) should be considered, with tapering when there is a sustained increase in ADAMTS 13 activity levels. (1B) PEX, with OctaplasLG should be started with 1.5 PV exchanges, and reassessed daily, reducing to 1.0 V when the clinical picture and laboratory tests are stabilising. (1A) Intensification in frequency and or volume of PEX procedures should be considered in life-threatening cases. (1B) Daily PEX should stop when the platelet count is sustained >150 × 10 9 /L. (2B) Monoclonal anti-CD20 therapy should be initiated within 3 days of acute iTTP admission. (1B) In patients who have refractory iTTP or have severe ADAMTS13 deficiency despite anti-CD20 therapy, alternative immunosuppressive therapy should be considered. (2B) Alternate immunomodulatory therapies, such as azathioprine, cyclophosphamide, splenectomy may be alternative options in patients with refractory or relapsing iTTP. (2C) All hospitalised/immobilised patients should receive thromboprophylaxis once platelet counts are ≥50 × 10 9 /L, even when treated with caplacizumab. (1B)