alvelestat (MPH966) / Mereo Biopharma 
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 15 Diseases   2 Trials   2 Trials   178 News 


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  • ||||||||||  Review, Journal:  Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD. (Pubmed Central) -  Sep 27, 2024   
    Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments.
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    No infection risk with alvelestat in patients with AATD in two phase 2 trials. (PS-9; Poster board no. 19) -  May 31, 2024 - Abstract #ERS2024ERS_1277;    
    Consistent with studies in COPD, bronchiectasis and cystic fibrosis, selective inhibition of NE in patients with AATD with alvelestat was not associated with increased frequency or severity of infection over the course of 12 weeks, including at the 240 mg bid proposed clinical dose. AESI ATALANTA Alvelestat 120 mg bid (N = 32) n (%) ASTRAEUS Alvelestat 120 mg bid (N = 22) n (%) ASTRAEUS Alvelestat 240 mg bid (N = 40) n (%) Placebo (N = 67) n (%) Infections 5 (15.6) 5 (22.7) 9 (22.5) 18 (26.9)
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    Trial completion:  ATALANTa: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (clinicaltrials.gov) -  Dec 15, 2023   
    P2,  N=63, Completed, 
    Trial completion date: Jan 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024 Active, not recruiting --> Completed
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Journal:  Neutrophil elastase remodels mammary tumors to facilitate lung metastasis. (Pubmed Central) -  Oct 5, 2023   
    To evaluate whether pharmacological inhibition of NE inhibited pulmonary metastasis and phenotypically mimicked PyMT NE-/- mice, we utilized AZD9668, a clinically available and specific NE inhibitor...Lastly, we identified a NE-specific signature that predicts recurrence and metastasis in breast cancer patients. Collectively, our studies suggest that genetic ablation and pharmacological inhibition of NE reduces metastasis and extends survival of mouse models of breast cancer, providing rationale to examine NE inhibitors as a treatment strategy for the clinical management of metastatic breast cancer patients.
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    Trial completion date, Trial primary completion date:  ATALANTa: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (clinicaltrials.gov) -  Aug 18, 2023   
    P2,  N=63, Active, not recruiting, 
    Collectively, our studies suggest that genetic ablation and pharmacological inhibition of NE reduces metastasis and extends survival of mouse models of breast cancer, providing rationale to examine NE inhibitors as a treatment strategy for the clinical management of metastatic breast cancer patients. Trial completion date: Aug 2023 --> Nov 2023 | Trial primary completion date: Aug 2023 --> Nov 2023
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Alvelestat worth 1b? Damn (Twitter) -  Jul 10, 2023   
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    Trial primary completion date:  ATALANTa: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (clinicaltrials.gov) -  Jun 15, 2023   
    P2,  N=63, Active, not recruiting, 
    Trial completion date: Aug 2023 --> Nov 2023 | Trial primary completion date: Aug 2023 --> Nov 2023 Trial primary completion date: Jun 2023 --> Aug 2023
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Alvelestat, an Oral Neutrophil Elastase Inhibitor in Alpha-1 Antitrypsin Deficiency (AATD): Results of a Phase II Trial (Walter E. Washington Convention Center, Ballroom B (Level 3)) -  Mar 25, 2023 - Abstract #ATS2023ATS_4080;    
    CONCLUSIONS Alvelestat demonstrated significant and consistent reduction in all 3 biomarkers related to AATD disease activity, with an acceptable safety profile. The magnitude of changes in desmosine and A?-val360 at the high dose were comparable to effects in placebo-controlled augmentation studies1,2 and support progression to Phase 3.
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    You mean Alvelestat? (Twitter) -  Oct 10, 2022   
  • ||||||||||  Elaspol (sivelestat) / Ono Pharma, alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Journal:  Novel benzoxazinone derivative as potent human neutrophil elastase inhibitor: Potential implications in lung injury. (Pubmed Central) -  Sep 10, 2022   
    While this inhibition is competitive based on substrate dilution assay, PD05 showed a high binding affinity for human neutrophil elastase (Kd = 1.63 nM) with faster association and dissociation rate compared to notable elastase inhibitors like ONO 6818 and AZD9668, and its interaction with human neutrophil elastase was fully reversible.Preclinical pharmacokinetic studies were performed in vitro where protein binding was found to be 72% with a high recovery rate, aqueous solubility of 194.7 μM, low permeability along with a favourable hERG...In mouse model PD05 is able to reduce the alveolar collapse induced by neutrophil elastase. In summary, we demonstrate the in situ, in vitro and in vivo anti-elastase potential of the newly synthesised benzoxazinone derivative PD05 and thus this could be promising candidate for further investigation as a drug for the treatment of COPD.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase. (Pubmed Central) -  Aug 30, 2022   
    Furthermore, our data using neutrophil elastase (NE) knock-out mice and the NE inhibitor AZD9668 suggest that neutrophils cause this damage by releasing NE and that inhibiting NE can prevent Dox-induced cardiotoxicity. This work shows the role of neutrophils and NE in Doxorubicin-induced cardiotoxicity for the first time and suggests a new possible therapeutic intervention.
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    Trial completion date, Trial primary completion date:  ATALANTa: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (clinicaltrials.gov) -  Aug 25, 2022   
    P2,  N=66, Recruiting, 
    This work shows the role of neutrophils and NE in Doxorubicin-induced cardiotoxicity for the first time and suggests a new possible therapeutic intervention. Trial completion date: Aug 2022 --> Aug 2023 | Trial primary completion date: Aug 2022 --> Apr 2023
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Journal:  The role of neutrophil elastase in aortic valve calcification. (Pubmed Central) -  Apr 12, 2022   
    Collectively, NE is highly involved in the pathogenesis of valve calcification. Targeting NE such as Alvelestat may be a potential treatment for CAVD.
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Preclinical, Journal:  Neutrophil-Associated Inflammatory Changes in the Pre-Diabetic Pancreas of Early-Age NOD Mice. (Pubmed Central) -  Dec 23, 2021   
    These findings add to the body of data supporting a role for neutrophils in the establishment of early pathology inside the pancreas, independently of, and earlier from the time at onset of lymphocytic infiltration. However, they also suggest that inhibition of neutrophils alone, acting via myeloperoxidase and neutrophil elastase only, in the absence of other other effector cells, is insufficient to alter the natural course of autoimmune diabetes, at least in the NOD model of the disease.
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Trial completion:  COSTA: COVID-19 Study of Safety and Tolerability of Alvelestat (clinicaltrials.gov) -  Nov 18, 2021   
    P1/2,  N=15, Completed, 
    However, they also suggest that inhibition of neutrophils alone, acting via myeloperoxidase and neutrophil elastase only, in the absence of other other effector cells, is insufficient to alter the natural course of autoimmune diabetes, at least in the NOD model of the disease. Active, not recruiting --> Completed
  • ||||||||||  alvelestat (MPH966) / Mereo Biopharma
    Trial completion date, Trial primary completion date:  ATALANTa: Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (clinicaltrials.gov) -  Sep 1, 2021   
    P2,  N=66, Recruiting, 
    Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022 Trial completion date: Aug 2021 --> Aug 2022 | Trial primary completion date: Aug 2021 --> Aug 2022
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Enrollment closed:  COSTA: COVID-19 Study of Safety and Tolerability of Alvelestat (clinicaltrials.gov) -  Aug 9, 2021   
    P1/2,  N=15, Active, not recruiting, 
    Trial completion date: Sep 2021 --> Apr 2022 | Trial primary completion date: Aug 2021 --> Mar 2022 Recruiting --> Active, not recruiting
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    [VIRTUAL] NEUTROPHIL ELASTASE INHIBITION IS PROTECTIVE IN EXPERIMENTAL MYELOPEROXIDASE ANTI NEUTROPHIL CYTOPLASMIC ANTIBODY VASCULITIS (HALL F) -  Apr 11, 2021 - Abstract #AUTO2021AUTO_363;    
    Further experiments using NE inhibitors Alvelestat and BAY 85-8501 given daily by oral gavage was administered to prevent NET formation.ResultsElane-/- animals were protected from excessive NET production and glomerular injury with significantly reduced kidney proinflammatory gene expression (IL-6, IL-1β, MCP-1 and CXCL2), segmental necrosis, numbers of glomerular neutrophils, extracellular MPO deposition, CD4 T cells, and macrophages influx (all, P <0.05 compared to WT)...With a significant reduction in the frequency of MPO specific CD4 effector T cells from the draining lymph nodes and a significant reduction in ANCA titre within the serum (P<0.05, compared with WT).ConclusionsNE inhibition attenuated inflammation through the reduction of pathological NETs. This data provides proof of concept evidence that targeting NE therapeutically may be of potential benefit in MPO-ANCA vasculitis.
  • ||||||||||  alvelestat (AZD9668) / AstraZeneca, Mereo Biopharma
    Trial completion date, Trial primary completion date:  ASTRAEUS: A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo. (clinicaltrials.gov) -  Jan 6, 2021   
    P2,  N=165, Recruiting, 
    These data indicate that NE inhibitor is a key treatment candidate to alleviate FUIIM by regulating abnormal inflammatory responses, intestinal barrier dysfunction, and gut microbiota imbalance. Trial completion date: Jul 2020 --> Sep 2021 | Trial primary completion date: Jun 2020 --> Aug 2021