- |||||||||| Tracleer (bosentan) / J&J, Roche
Journal: Endothelin-1-mediated Drug Resistance in EGFR-mutant NSCLC. (Pubmed Central) - Feb 13, 2021
Furthermore, depletion of EDN1 or the use of endothelin receptor inhibitors bosentan and ambrisentan improved drug penetration into tumors and restored blood flow in tumor-associated vasculature. Correlatively, these results describe a simplistic endogenous yet previously unrealized resistance mechanism inherent to a subset of EGFR-mutant NSCLC to attenuate TKI delivery to the tumors by limiting drug-carrying blood flow and the drug concentration in tumors.
- |||||||||| ambrisentan / Generic mfg.
Clinical, Journal: Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial. (Pubmed Central) - Jan 23, 2021
P3
Ambrisentan monotherapy in PoPH improves hemodynamics and FC at 24 weeks; however, it did not show any improvement in 6MWD. These preliminary outcomes should be interpreted with caution (Clinicaltrials.Gov:NCT01224210).
- |||||||||| ambrisentan / Generic mfg.
Trial completion, Phase classification, Trial completion date: Portopulm: Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial (clinicaltrials.gov) - Jan 12, 2021
P3, N=30, Completed,
Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis. Active, not recruiting --> Completed | Phase classification: PN/A --> P3 | Trial completion date: Oct 2020 --> Mar 2020
- |||||||||| Adempas (riociguat) / Bayer, Opsumit (macitentan) / Nippon Shinyaku, J&J, Tracleer (bosentan) / J&J, Roche
[VIRTUAL] Assessment of system-wide hospital compliance with inpatient oral pulmonary hypertension Risk Evaluation and Mitigation Strategies programs () - Dec 26, 2020 - Abstract #ASHP2020ASHP_1807;
During June 2020, AdventHealth Orlando was selected to participate in an audit reviewing compliance with the newly developed shared ambrisentan REMS...Further evaluation of inpatient compliance is required of all oral pulmonary hypertension medication REMS programs including bosentan, macitentan, and riociguat...All patients that meet the inclusion criteria will be included in the analysis. Compliance with required REMS criteria and appropriate documentation per institutional policies will be evaluated for selected agents.
- |||||||||| ambrisentan / Generic mfg., tadalafil / Generic mfg.
Review, Journal: Pulmonary arterial hypertension: Rationale for using multiple vs. single drug therapy. (Pubmed Central) - Nov 6, 2020
In the near future, up-front triple therapy may be emerge as bona fide treatment approach in selected patients. Future goals that are already under consideration in PAH include stronger integration of pathobiological characteristics when considering the use of specific drugs, or the development of novel therapies, toward precision medicine-based clinical pharmacology.
- |||||||||| ambrisentan / Generic mfg.
[VIRTUAL] ETA Receptor Blockade and Vascular Function in Patients with Sickle Cell Disease (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2185;
We earlier reported on our studies on the role of ET-1 in SCD, and in transgenic mouse models showed that ETA receptor blockade with ambrisentan provides renal protection by preventing the development of glomerular hyperfiltration and proteinuria (Kasztan et al, 2017, Taylor et al, 2019, Kasztan and Pollock, 2019)...Increase in blood flow velocity in major intracranial vessels is a well established risk factor for ischemic stroke in children with SCD; however, much less is known in adults. In summary, the effect of ETA receptor blockade with or without ACEi/ARB, may have a significant effect on vascular function/blood flow in different organ systems, and should be explored in a large, multi-center phase II trial, with and without concomitant and or serial ACEi/ARBs, for a longer period of time, with a dose escalation, to further clarify the pleiotropic effects on multiple aspects of SCD pathology.
- |||||||||| Tyvaso (treprostinil) / United Therapeutics
Clinical, Journal: Implantable LENUS pro pump for treprostinil infusion in three pediatric patients. (Pubmed Central) - Oct 27, 2020
In summary, the effect of ETA receptor blockade with or without ACEi/ARB, may have a significant effect on vascular function/blood flow in different organ systems, and should be explored in a large, multi-center phase II trial, with and without concomitant and or serial ACEi/ARBs, for a longer period of time, with a dose escalation, to further clarify the pleiotropic effects on multiple aspects of SCD pathology. Implantable pumps for continuous parenteral prostanoid infusion in pediatric patients are an alternative to external pumps, especially when familiar psychological or psychomotor issues hinder the use of external pumps.
- |||||||||| Thelin (sitaxsentan) / Pfizer, Tracleer (bosentan) / J&J, Roche
Clinical, Journal: Liver safety evaluation of endothelin receptor antagonists using HepatoPac : A single model impact assessment on hepatocellular health, function and bile acid disposition. (Pubmed Central) - Oct 16, 2020
Differences across hepatocellular health (cellular adenosine triphosphate/glutathione content), function (urea production/albumin secretion) and taurocholic acid transport (biliary clearance/excretion index) were compared using amiodarone and ciclosporin A as positive controls...Although traditional animal testing provides adequate safety coverage for advancement of novel pharmaceuticals into clinical trials, supplemental assays employing human MPCCs may strengthen weight-of-evidence predictions for sensitive human populations. Proving the predictive value of this single impact assessment model in advance of clinical trial information for human liver injury risk is needed across more pharmaceuticals.
- |||||||||| treprostinil inhaled dry powder (LIQ861) / Liquidia Technologies
[VIRTUAL] CLINICAL IMPACT OF LIQ861 THROUGH ASSESSMENT BY THE CARDIOMEMS SYSTEM IN PULMONARY ARTERIAL HYPERTENSION: A CASE STUDY () - Oct 12, 2020 - Abstract #CHEST2020CHEST_2473;
This case illustrates an additive and favorable clinical, hemodynamic, and RV remodeling response to LIQ861 and the utility of the CardioMEMS™ system to monitor disease progression. CLINICAL IMPLICATIONS: The combination of CardioMEMS™-derived hemodynamic and adjunctive clinical information can inform clinical decisions regarding advancement in therapy and optimizing clinical status.
- |||||||||| ambrisentan / Generic mfg., hydroxychloroquine / Generic mfg., prednisone / Generic mfg.
[VIRTUAL] PULMONARY ARTERIAL HYPERTENSION AS A MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOUS () - Oct 12, 2020 - Abstract #CHEST2020CHEST_2374;
This case highlights the close link between autoimmune conditions, small-vessel pulmonary vascular changes related to lymphoid aggregation and pulmonary hypertension. Targeted treatment for both group 1 PAH and SLE should be considered early in such patients, and initiated without delay.
- |||||||||| ambrisentan / Generic mfg., Tracleer (bosentan) / J&J, Roche
[VIRTUAL] Regulatory Policies for the Financing of Orphan Drugs () - Oct 3, 2020 - Abstract #ISPOREU2020ISPOR-EU_622;
On the contrary, Volibris® (ambrisentan) will soon have generic marketed with a possible decrease of 60% and, if it appears in the RPO, the presentation of less doses could decrease up to 80%. CONCLUSIONS : New economic models, such as risk-sharing agreements, could be a good alternative to favor the development of safe and effective treatments accessible to patients and, in turn, achieve the sustainability of the National Health System.
- |||||||||| Uptravi (selexipag) / J&J, Nippon Shinyaku, Opsumit (macitentan) / Nippon Shinyaku, J&J
Clinical, Journal: Enrichment Benefits of Risk Algorithms for Pulmonary Arterial Hypertension Clinical Trials. (Pubmed Central) - Sep 17, 2020
Several ophthalmologic findings have been described associated with PH. This preliminary study demonstrates the feasibility of risk algorithms for pulmonary arterial hypertension trial enrichment and a need for further investigation.
- |||||||||| tacrolimus / Generic mfg.
[VIRTUAL] De Novo Pulmonary Arterial Hypertension After Heart Transplantation (Poster Hall - ePosters) - Sep 10, 2020 - Abstract #HFSA2020HFSA_382;
Post-transplant he was treated with tacrolimus and mycophenolate...He was treated with tadalafil, ambrisentan, and amlodipine with an improvement in functional class...Figure 1. Results of serial right heart catheterizations
- |||||||||| ambrisentan / Generic mfg.
Trial completion: Drug Use Investigation for VOLIBRIS (clinicaltrials.gov) - Sep 3, 2020
P=N/A, N=900, Completed,
Results of serial right heart catheterizations Active, not recruiting --> Completed
- |||||||||| ambrisentan / Generic mfg.
Journal: Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis. (Pubmed Central) - Aug 19, 2020
Several compounds, including 2-oxypyrimidine containing structural analogs of the marketed endothelin receptor A antagonist Ambrisentan, were identified as hits from the screen...Additionally, x-ray crystallography studies identified key amino acid residues in the binding pocket present in human IL-36γ that are absent in human IL-36α. A-552 represents a first-in-class small molecule antagonist of IL-36 signaling that could be used as a chemical tool to further investigate the role of this pathway in inflammatory skin diseases such as psoriasis.
- |||||||||| ambrisentan / Generic mfg.
Journal: Implication of Differential Surface Anisotropy on Biopharmaceutical Performance of Polymorphic Forms of Ambrisentan. (Pubmed Central) - Aug 12, 2020
Pre and post intrinsic dissolution compact studied by atomic force microscopy (AFM) showed a significant difference in surface roughness and defects formation in form II as compared to form I which is attributed to the presence of more hydrophilic surfaces. The hydrophilic molecular surface environment of form II is ascribed to its improved intrinsic dissolution rate (IDR) than form I. Further, in-vivo pharmacokinetic study also showed significantly higher AUC and C in form II compared to form I. Overall, this study demonstrates that form I & II of AMT exhibited the differential surface anisotropy which has significant implications on their biopharmaceutical performance.
- |||||||||| tilarginine (L-NMMA) / Arginox Pharma, Houston Methodist Research Institute, NN1213 / Novo Nordisk
Enrollment open: Mechanisms of Cerebrovascular Control (clinicaltrials.gov) - Aug 10, 2020
P1, N=60, Recruiting,
The hydrophilic molecular surface environment of form II is ascribed to its improved intrinsic dissolution rate (IDR) than form I. Further, in-vivo pharmacokinetic study also showed significantly higher AUC and C in form II compared to form I. Overall, this study demonstrates that form I & II of AMT exhibited the differential surface anisotropy which has significant implications on their biopharmaceutical performance. Suspended --> Recruiting
- |||||||||| ambrisentan / Generic mfg., Opsumit (macitentan) / Nippon Shinyaku, J&J, Tracleer (bosentan) / J&J, Roche
Clinical, Retrospective data, Journal: The Clinical Efficacy of Endothelin Receptor Antagonists in Patients with Pulmonary Arterial Hypertension. (Pubmed Central) - Aug 8, 2020
Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.
- |||||||||| Biomarker, Journal, Combination therapy: Risk reduction and right heart reverse remodeling by upfront triple combination therapy in pulmonary arterial hypertension. (Pubmed Central) - Jul 31, 2020
P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan. Triple upfront combination therapy with ambrisentan, tadalafil and subcutaneous treprostinil in severe non-reversible PAH is associated with considerable clinical and hemodynamic improvement and right heart reverse remodeling.
- |||||||||| tilarginine (L-NMMA) / Arginox Pharma, Houston Methodist Research Institute, NN1213 / Novo Nordisk
Trial completion date, Trial primary completion date: Mechanisms of Cerebrovascular Control (clinicaltrials.gov) - Jul 15, 2020
P1, N=60, Suspended,
The treatment response score helps clinicians in predicting treatment failure at the time of diagnosis. Trial completion date: Jul 2020 --> Jul 2021 | Trial primary completion date: Jul 2020 --> Jul 2021
- |||||||||| ambrisentan / Generic mfg., imatinib / Generic mfg., sildenafil / Generic mfg.
[VIRTUAL] A Unique Case of Pulmonary Tumor Thrombotic Microangiopathy (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_7213;
Additionally, sildenafil and ambrisentan have also shown some benefit. Due to the highly fatal disease, further studies aiming at improving our survival in PTTM should be undertaken.
- |||||||||| Remodulin (treprostinil diethanolamine oral) / United Therapeutics, ambrisentan / Generic mfg., tadalafil / Generic mfg.
[VIRTUAL] Pulmonary Capillary Hemangiomatosis; Pathologic Findings of a Rare Cause of Pulmonary Hypertension (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_7187;
DISCUSSION Pulmonary capillary hemangiomatosis is a rare, progressive disease and can ultimately only be confirmed with biopsy and pathological analysis. The vascular invasion characteristic of PCH often results in a secondary veno-occlusive phenomenon which can explain hypoxemia, vascular congestion and right-heart failure, and is almost always uniformly fatal.
- |||||||||| Benlysta (belimumab) / GSK, cyclophosphamide intravenous / Generic mfg.
[VIRTUAL] Belimumab in the Treatment of Interstitial Lung Disease Associated with Systemic Lupus Erythematosus (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_6519;
Cyclophosphamide was switched to azathioprine in view of hemorrhagic cystitis...As demonstrated in our case, Belimumab also has the potential to delay ILD associated with CTDs progression and improve clinical outcomes. To our knowledge there has been no formal study to quantify the effects of Belimumab in patients with CTD associated ILD and is a potential venue to explore.
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