TIM1

The annual meeting of the American Society of Nephrology (Kidney Week) was held this year from Oct. 23 to 27 in San Diego, attracting attendees from around the world, including nephrology specialists, researchers, scientists, and other health care professionals. The conference featured presentations focusing on the latest advances in the management of patients with kidney diseases and related disorders. In one study, Hardik Dineshbhai Desai, M.B.B.S., of the Gujarat Adani Institute of Medical Science in Bhuj, India, and colleagues found that chronic kidney disease (CKD) attributable to metabolic risk factors nearly tripled in women in terms of mortality between 1990 and 2021, with significant regional and income-related disparities evident. The authors analyzed data from the Global Burden of Disease 2021 study and found that the annual percentage change (APC) in deaths due to CKD attributable to metabolic risk factors in women increased 3.39 percent from 1990 to 2021. While total percentage change in death increased by 180.91 percent (nearly tripled/close to threefold from 1990 to 2021), the growth rate, as indicated by the APC, has remained fairly consistent across decades, showing a slight upward trend in the most recent period (2010 to 2021). Regionally, the highest APC in incidence was observed in Andean Latin America (3.52 percent) and Central Latin America (3.03 percent). In terms of World Health Organization income level, the highest APC in incidence was observed in middle-income regions, followed by high-income regions. For the mortality rate, the highest APC was observed in high-income regions (3.23 percent). "This calls for urgent global health strategies focusing on prevention, early detection, and management of CKD, especially in regions and populations most at risk," Desai said. "Clinicians should focus on gender-sensitive screening for CKD, especially targeting women with a history of gestational diabetes or preeclampsia, as these conditions are linked to an increased risk of future metabolic syndrome and renal impairment. Integrating nephrology and women's health in clinical practice can enhance early detection and intervention, thus improving outcomes." Press Release In another study, Giselle Peschard, M.D., of the University of California in San Francisco, and colleagues found that integrating multiple biomarkers into distinct kidney health dimensions provides valuable insights into the biological processes underlying CKD in individuals with diabetes. Novel dimensions of kidney health were developed by combining a set of 17 urine and plasma biomarkers that had been individually associated with CKD progression in prior studies. The authors evaluated findings from two cohorts that included persons with diabetes and CKD: the National Institute of Diabetes and Digestive and Kidney Diseases Chronic Renal Insufficiency Cohort (CRIC) and the REasons for Geographic And Racial Differences in Stroke. The researchers identified three kidney health dimensions, which were labeled as follows: systemic inflammation and filtration score (including plasma TNFR-1, TNFR-2, suPAR, and SDMA); tubular function score (including urine EGF, ADMA, and SDMA); and tubular damage score (including urine α1m, KIM-1, and MCP-1). Each was associated with CKD progression or mortality, independent of clinical risk factors, estimated glomerular filtration rate (eGFR), and albuminuria. The investigators noted that higher tubular damage and lower tubular function scores were associated with a higher risk for CKD progression in CRIC, while higher systemic inflammation and filtration scores were associated with a higher mortality risk in both cohorts. "Predominantly capturing the health of the kidney tubules, our findings demonstrate that there are important indicators of kidney health beyond the current clinical measures of eGFR and albuminuria," Peschard said. "These kidney health dimensions may help us to understand the heterogeneity of CKD patterns and risk for persons with diabetes." Press Release Millie Shah, Ph.D., from Biogen in Cambridge, Massachusetts, and colleagues furthered the understanding of the role of CD38+ antibody-secreting cells (plasma cells and plasmablasts) in immunoglobulin A nephropathy (IgAN) pathogenesis. The authors evaluated whole blood and serum collected from patients with IgAN before, during, and after felzartamab treatment. The investigators found that the targeting of CD38+ plasma cells and plasmablasts with felzartamab resulted in durable reductions of disease-relevant biomarkers in IgAN study participants. Disease-associated IgA and galactose-deficient IgA1 were reduced following felzartamab treatment and remained reduced for at least 18 months and up to 10 months off-treatment, respectively. In contrast, the body's IgG titers were modestly reduced and recovered within four months off-treatment, suggesting the preservation of components of the body's adaptive immune response. "Direct depletion of CD38+ cells may offer clinical benefit without continuous dosing, potentially lowering patient burden and offering improved tolerability," Shah said. "Further study of felzartamab treatment in IgAN is planned in an upcoming phase 3 study." The study was funded by Biogen, which is developing felzartamab. Press Release ASN: 1990 to 2021 Saw Global Rise in Chronic Kidney Disease Cases, Deaths in Women FRIDAY, Nov. 1, 2024 -- Chronic kidney disease cases and deaths in women surged worldwide between 1990 and 2021, according to a study presented at Kidney Week, the annual meeting of the American Society of Nephrology, held from Oct. 23 to 27 in San Diego. Read Full Text ASN: Atrasentan Significantly and Clinically Meaningfully Cuts Proteinuria WEDNESDAY, Oct. 30, 2024 -- Atrasentan is associated with a significant and clinically meaningful reduction in proteinuria compared with placebo in patients with immunoglobulin A nephropathy, according to a study published online Oct. 25 in the New England Journal of Medicine to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held from Oct. 23 to 27 in San Diego. Read Full Text ASN: Hypertension Most Common Cardiovascular Comorbidity Seen With Dialysis WEDNESDAY, Oct. 30, 2024 -- Hypertension is the most common cardiovascular disease comorbidity seen among dialysis patients globally, according to a study presented at Kidney Week, the annual meeting of the American Society of Nephrology, held from Oct. 23 to 27 in San Diego. Read Full Text ASN: Empagliflozin Offers Lasting Cardiorenal Benefit in CKD Patients MONDAY, Oct. 28, 2024 -- Empagliflozin continues to offer cardiorenal benefits for up to 12 months after discontinuation among patients with chronic kidney disease at risk for progression, according to a study published online Oct. 25 in the New England Journal of Medicine to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held from Oct. 23 to 27 in San Diego. Read Full Text ASN: Recurrent UTIs Impact eGFR in Children With Vesicoureteral Reflux MONDAY, Oct. 28, 2024 -- For children with vesicoureteral reflux, recurrent urinary tract infections are associated with a decrease in estimated glomerular filtration rate, according to a research letter published online Oct. 24 in JAMA Pediatrics to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held from Oct. 23 to 27 in San Diego. Read Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

1.Theravance Biopharma: Yupelri (revfenacin)Indication: Chronic Obstructive Pulmonary Disease (COPD) Clinical Trials: Phase 4 On January 5th, Theravance Biopharma announced that the Phase IV PIFR-2 study of Yupelri (revefenacin) inhalation solution for the maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD) did not meet the primary endpoint. Yupelri is the only once-daily nebulized long-acting muscarinic antagonist (LAMA) approved in the United States for the maintenance treatment of COPD. The PIFR-2 study aimed to evaluate the improvement in lung function of Yupelri as compared to tiotropium bromide (Spiriva, a dry powder inhaler) in patients with severe to very severe COPD. The study results showed that on day 85, there was no statistically significant difference in the primary endpoint of change from baseline in trough Forced Expiratory Volume in one second (FEV1) compared to the control group. The safety and tolerability profile of Yupelri was consistent with previous studies. 2. Novartis: LigelizumabIndication: peanut allergy Clinical Trials: Phase 3 On January 16th, the clinicaltrials.gov website indicated that Novartis has discontinued the Phase III clinical trial for the treatment of peanut allergy with the immunoglobulin E (IgE) monoclonal antibody Ligelizumab (study CQGE031G12301). This study was a multicenter, randomized, double-blind, placebo-controlled clinical trial, which initially aimed to enroll 486 patients medically diagnosed with IgE-mediated peanut allergy, to evaluate the efficacy and safety of Ligelizumab (120/240mg, once a month) compared to a placebo. As of the termination date of the trial, 211 patients had been enrolled. This termination marks the second setback encountered by Ligelizumab in the immunotherapy field. In September 2023, Novartis formally terminated the Phase III PEARL-PROVOKE study for the treatment of chronic inducible urticaria (CIU) with Ligelizumab, due to the drug not demonstrating a significant therapeutic advantage in two Phase III studies (PEARL 1 and PEARL 2) for the treatment of chronic spontaneous urticaria (CSU). Although Ligelizumab was more effective than a placebo, it was less effective than omalizumab. 3. Allakos: lirentelimabIndication: Chronic Spontaneous Urticaria Clinical Trials: Phase 2 On January 16th, Allakos announced that lirentelimab did not meet the primary endpoints in the Phase 2 clinical trial (ATLAS) for patients with atopic dermatitis and the Phase 2b clinical trial (MAVERICK) for patients with chronic spontaneous urticaria. The results of the Phase 2b clinical trial (ATLAS) for the treatment of atopic dermatitis patients with lirentelimab showed that, at the primary endpoint after treatment to achieve EASI-75, 23% of patients treated with lirentelimab reached EASI-75 compared to 18% of patients treated with placebo, which was not statistically significant. In the MAVERICK trial, for the primary endpoint on the reduction of the UAS7 score, patients treated with lirentelimab saw a 27% reduction in UAS7 compared to a 26% reduction in the placebo-treated group, which also lacked statistical significance. 4. Gilead: Trodelvy® (sacituzumab-govitecan-hziy; SG)Indication: non-small cell lung cancer (NSCLC) Clinical Trials: Phase 3 On January 22, Gilead announced that its Trop2 ADC (antibody-drug conjugate) new drug, Trodelvy, did not meet the primary OS (overall survival) endpoint in the Phase III clinical trial EVOKE-01 for the treatment of non-small cell lung cancer (NSCLC). EVOKE-01 is assessing the efficacy of the Trop2 ADC drug Trodelvy® (sacituzumab govitecan-hziy; SG) in combination with docetaxel in patients with metastatic or advanced NSCLC who have progressed during or after treatment with platinum-based chemotherapy and checkpoint inhibitors. Trodelvy is a Trop-2 targeting ADC monoclonal antibody drug. Trop-2 is a transmembrane glycoprotein whose high expression is associated with the occurrence of many tumors and poorer prognosis, making it a very popular target for ADC research, second only to HER2 in terms of interest. Currently, Gilead's Trop-2 ADC drug Trodelvy is the only one approved globally for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have previously received at least two therapies, and for patients with locally advanced or metastatic urothelial carcinoma (UC). 5. BMS: OpdivoIndication: Second Time in Late-Stage Kidney Cancer Clinical Trials: Phase 3 On January 29, Bristol-Myers Squibb (BMS) announced the failure of its PD-1 inhibitor, Opdivo, in Part B of the Phase III CheckMate-914 study, as it did not provide a significant benefit in disease-free survival for patients at high risk of recurrence after local renal cell carcinoma surgery. CheckMate-914 is a randomized, double-blind, two-part trial. In Part B, the study compared monotherapy with Opdivo to a placebo. The trial was designed to assess its use as an adjuvant treatment for renal cell carcinoma (RCC) patients who have undergone complete or partial nephrectomy and are at intermediate or high risk of recurrence. After a median follow-up of 27 months, Opdivo failed to demonstrate a significant improvement in disease-free survival (DFS) as compared to placebo, with a hazard ratio of 0.87 and a p-value of 0.3952 based on an assessment by blinded independent central review (BICR). The 12-month DFS probability for the Opdivo group was 83.3%, compared with 78.2% for the placebo group. At 18 months, these estimates changed only slightly to 78.4% and 75.4%, respectively. At the time of analysis, the median DFS for both treatment groups had not been reached. 6. Laekna: afuresertibIndication: platinum-resistant ovarian cancer (PROC) Clinical Trials: Phase 2 On January 29, Laekna Pharma announced the top-line data from the PROFECTA-II study for the combination of afuresertib with paclitaxel in the treatment of platinum-resistant ovarian cancer (PROC). The PROFECTA-II study (NCT04374630) is a randomized, open-label, active-controlled phase II clinical trial evaluating the efficacy and safety of the combination of afuresertib and paclitaxel compared to paclitaxel alone in female patients with platinum-resistant ovarian cancer (PROC). The study enrolled 150 patients randomly across the United States and China into both the experimental and control groups. The primary endpoint was progression-free survival as assessed by the researchers, while secondary endpoints included overall survival, objective response rate, and duration of response. Trial results indicated that the combination treatment of afuresertib and paclitaxel reduced the risk of disease progression or death (progression-free survival, PFS), with an HR of 0.744 (95% CI: 0.502-1.102); however, the results were not statistically significant. 7. Novartis: sabatolimabIndication: intermediate, high, or very high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia-2 (CMML-2) Clinical Trials: Phase 3 On January 31, in its 2023 financial report, Novartis provided updates on its pipeline progress, revealing that the phase III STIMULUS MDS2 study of its TIM-3 monoclonal antibody, sabatolimab (MBG453), in combination therapy for intermediate, high, or very high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia-2 (CMML-2), did not meet its primary endpoint of overall survival (OS). As a result, Novartis has removed it from its pipeline. Moreover, Novartis has also decided to discontinue the development of the BTK inhibitor remibrutinib for the treatment of Sjögren’s syndrome. TIM-3 is a receptor protein belonging to the T cell immunoglobulin and mucin domain (TIM) family that is expressed on the surfaces of T cells, regulatory T cells (Tregs), and innate immune cells (including dendritic cells, natural killer cells, and monocytes). Previously, Novartis had posited that sabatolimab could act by inhibiting the function of the TIM-3 receptor, thereby targeting both myeloid leukemia cells and immune cells simultaneously. This inhibition was hoped not only to kill cancer cells but also potentially enhance the vigor of immune cells.

LAPIX Therapeutics, Inc. (“LAPIX”), a biopharmaceutical company focused on developing novel, orally bioavailable immune system restoration therapies for autoimmune diseases, today announced that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial for its first-in-class, immune tolerance restoration small molecule, LPX-TI641, for the treatment of multiple sclerosis (MS). The clinical trial is expected to begin dosing in 4Q 2023. “We believe in empowering and restoring the immune system to fight disease and the FDA clearance of our IND application for LPX-TI641 represents momentum in our technology and scientific approach,” said Anas M. Fathallah, Ph.D., Chief Executive Officer and co-founder of LAPIX. “We are excited to begin our first-in-human clinical study evaluating LPX-TI641 and its potential to be a first of its kind non-immune suppressive therapeutic option for autoimmune diseases.” The Phase 1 trial is designed to evaluate the safety, tolerability, and pharmacokinetics of LPX-TI641 in healthy subjects after a single ascending dose. Data from the Phase 1 study along with LPX-TI641’s antigen-agnostic versatility could allow for the rapid pivot to other autoimmune indications such as rheumatoid arthritis. “We aspire to transform how the medical field treats patients diagnosed with serious and complex immune diseases and we are deeply committed to helping as many people as possible,” added Dr. Fathallah. “Our antigen-agnostic immune tolerance restoration approach centered on developing Tim (T-cell immunoglobulin and mucin domain) agonists, along with our in-depth knowledge of immunology and immune tolerance are the keys to unlocking transformative therapies for patients with additional consideration for their quality of life.” About LPX-TI641 LPX-TI641 is an investigational, novel, and proprietary orally bioavailable small molecule T cell immunoglobulin and mucin domain-containing protein (TIM) 3/4 receptor agonist. The TIM family of receptors play an important role in autoimmunity. LPX-TI641’s primary pharmacology is the upregulation of Foxp3+/DC4+ T-cells (T-regs) and of Tim1+/CD25+/CD19+ (B-regs) and inhibition/downregulation of Th17. The combined effects of LPX-TI641’s pharmacology is to allow the adaptive immune system to re-establish self-tolerance (T-reg/Th17 balance and B-regs) without affecting the innate immune system. The efficacy of LPX-TI641 versus standards of care has been evaluated in several animal models of MS and those models have shown favorable efficacy of LPX-TI641 in treatment escalation and treatment induction/maintenance paradigms mimicking current clinical management paradigms of MS without inducing neutropenia or lymphocytopenia. It is currently under development for neuro-autoimmune indications such as MS, with the intent to expand into rheumatoid arthritis amongst other autoimmune conditions. About LAPIX Therapeutics LAPIX Therapeutics Inc. is a Boston, MA-based company in the biopharma sector, focused on developing novel, orally bioavailable immune system restoration therapies, including immune tolerance restoration therapy for autoimmune diseases, immune tolerance induction therapies for gene therapy, and immune function restoration therapies for oncology. To learn more, visit www.lapix.com or follow us on LinkedIn and Twitter. The content above comes from the network. if any infringement, please contact us to modify.