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46 News |  |
- | emvododstat (PTC299) / PTC Therap
Retrospective data, Journal: Quantitative Systems Toxicology Modeling Informed Safe Dose Selection of Emvododstat in Acute Myeloid Leukemia Patients. (Pubmed Central) - Feb 19, 2024
Overall, retrospective DILIsym simulations adequately predicted the liver safety liabilities of emvododstat in solid tumor trials and prospective simulations predicted the liver safety of reduced doses in an AML clinical trial. The modeling was critical to enabling regulatory approval to proceed with the AML clinical trial wherein the predicted liver safety was confirmed.
- || emvododstat (PTC299) / PTC Therap
PK/PD data, Journal: A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor. (Pubmed Central) - Jun 6, 2023
Emvododstat appears to be a strong CYP2D6 inhibitor. No drug-related treatment emergent adverse effects (TEAEs) were considered to be severe or serious.
- || emvododstat (PTC299) / PTC Therap
PK/PD data, Journal: A pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor. (Pubmed Central) - Mar 21, 2023
Emvododstat can be safely administered with other BCRP substrate drugs. Hence, pharmacokinetic DDI mediated via BCRP inhibition is not expected when emvododstat and BCRP substrates are coadministered.
- | emvododstat (PTC299) / PTC Therap
Preclinical, Journal: Absorption, Distribution, Metabolism and Excretion of C-Emvododstat following a Single Oral Dose in Rats and Dogs. (Pubmed Central) - Jan 27, 2023
Emvododstat was the dominant radioactive component in plasma and faeces.Following a single oral dose of C-emvododstat in dogs, 75.2% of the dose was recovered in faeces while 0.5% of dose was recovered in urine 8 days post-dose. Emvododstat was the dominant radioactive component in faeces, while emvododstat and its two metabolites (O-desmethyl emvododstat and emvododstat amide bond hydrolysis product) were the major circulating radioactivity in dog plasma.
- | emvododstat (PTC299) / PTC Therap
Enrollment change, Trial termination: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Jan 13, 2023
P2/3, N=189, Terminated, Sponsor: PTC Therapeutics
Emvododstat was the dominant radioactive component in faeces, while emvododstat and its two metabolites (O-desmethyl emvododstat and emvododstat amide bond hydrolysis product) were the major circulating radioactivity in dog plasma. N=380 --> 189 | Recruiting --> Terminated; Sponsor decision
- | emvododstat (PTC299) / PTC Therap
Journal: SAR studies toward discovery of emvododstat (PTC299), a potent dihydroorotate dehydrogenase (DHODH) inhibitor. (Pubmed Central) - Nov 22, 2022
Emvododstat (PTC299) is a tetrahydro-β-carboline DHODH inhibitor discovered through the GEMS technology (Gene Expression Modulation by Small-Molecules). Described in this paper is the lead optimization campaign that culminated in the discovery of this highly potent DHODH inhibitor.
- |||| emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Apr 27, 2022
P2/3, N=380, Recruiting, Sponsor: PTC Therapeutics
Described in this paper is the lead optimization campaign that culminated in the discovery of this highly potent DHODH inhibitor. Trial completion date: Mar 2022 --> Jun 2022 | Trial primary completion date: Mar 2022 --> Jun 2022
- || emvododstat (PTC299) / PTC Therap
PK/PD data, Preclinical, Journal: In Vitro Metabolism, Pharmacokinetics and Drug Interaction Potentials of Emvododstat, a DHODH Inhibitor. (Pubmed Central) - Apr 23, 2022
Neither emvododstat nor O-desmethyl emvododstat was a substrate for common efflux or uptake transporters investigated.Emvododstat is bioavailable in mice, rats, dogs, and monkeys following a single oral dose. The absorption was generally slow with the mean plasma T ranging from 2 to 5 h; plasma exposure of O-desmethyl emvododstat was lower in rodents, but relatively higher in dogs and monkeys.
- || emvododstat (PTC299) / PTC Therap
Review, Journal: Recent advances of human dihydroorotate dehydrogenase inhibitors for cancer therapy: Current development and future perspectives. (Pubmed Central) - Mar 17, 2022
In recent years, in exploiting novel structural hDHODH inhibitors (hDHODHi), a candidate drug PTC299 has entered clinical trials for treating acute myelocytic leukemia (AML) and other tumors. This review discusses tumor-related research of hDHODH and highlights the structure-activity relationships of hDHODHi, providing insights into new drugs targeting hDHODH for antitumor clinical practice.
- | emvododstat (PTC299) / PTC Therap
Preclinical, Journal: Emvododstat, a Potent Dihydroorotate Dehydrogenase Inhibitor, Is Effective in Preclinical Models of Acute Myeloid Leukemia. (Pubmed Central) - Mar 1, 2022
DHO levels declined as drug levels declined, consistent with the reversibility of DHODH inhibition by emvododstat. These preclinical findings provide a rationale for clinical evaluation of emvododstat in an ongoing Phase 1 study of patients with relapsed/refractory acute leukemias.
- |||| emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Feb 6, 2022
P2/3, N=380, Recruiting, Sponsor: PTC Therapeutics
These preclinical findings provide a rationale for clinical evaluation of emvododstat in an ongoing Phase 1 study of patients with relapsed/refractory acute leukemias. Trial completion date: Dec 2021 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Mar 2022
- ||| emvododstat (PTC299) / PTC Therap
Trial completion date, Trial termination, Trial primary completion date: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Feb 2, 2022
P1b, N=33, Terminated, Sponsor: PTC Therapeutics
Trial completion date: Dec 2021 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Mar 2022 Trial completion date: May 2022 --> Dec 2021 | Recruiting --> Terminated | Trial primary completion date: Apr 2022 --> Dec 2021; Sponsor terminated the study.
- | Journal: Antiviral treatment of COVID-19: An update. (Pubmed Central) - Jan 4, 2022
The main drug groups include inhibitors of viral entry into the human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, human soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), inhibitors of viral proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), inhibitors of viral RNA (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), inhibitors of host proteins supporting virus (plitidepsin, fluvoxamine, ivermectin), and agents supporting host natural immunity...Additional studies are needed to define the role of remdesivir, favipiravir, interferons, ivermectin, dutasteride, proxulutamide, fluvoxamine, bromhexine, nitazoxanide and niclosamid in the treatment of COVID-19. Finally, the results of phase trials are waited to learn whether or not the newer agents such as molnupiravir, PF-07321332, PF-07304814, plitidepsin and AT-527 are effective in the treatment of COVID-19.
- emvododstat (PTC299) / PTC Therap
Inhibition of De Novo Pyrimidine Synthesis Depletes Acute Myleogenous Leukemia Stem Cells (LSCs) Burden and Triggers Apoptosis and Differentiation Associated with Oxidative Stress (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3867;
Emvododstat is a novel dihydroorotate dehydrogenase inhibitor being tested in a clinical trial for the treatment of myeloid malignancies and COVID-19. Keywords: AML, emvododstat, DHODH, apoptosis, differentiation.
- | emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Oct 20, 2021
P1b, N=39, Recruiting, Sponsor: PTC Therapeutics
Keywords: AML, emvododstat, DHODH, apoptosis, differentiation. Trial completion date: Jun 2021 --> May 2022 | Trial primary completion date: May 2021 --> Apr 2022
- |||| emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Oct 19, 2021
P2/3, N=380, Recruiting, Sponsor: PTC Therapeutics
Trial completion date: Jun 2021 --> May 2022 | Trial primary completion date: May 2021 --> Apr 2022 Trial completion date: Jul 2021 --> Dec 2021 | Trial primary completion date: Jul 2021 --> Dec 2021
- emvododstat (PTC299) / PTC Therap
[VIRTUAL] Emvododstat (PTC299) Targets De Novo Pyrimidine Synthesis in Acute Myeloid Leukemia () - Sep 6, 2021 - Abstract #SOHO2021SOHO_442;
Inhibition of de novo pyrimidine synthesis triggers differentiation, apoptosis, and/or inhibition of proliferation in AML models. Emvododstat is a novel dihydroorotate dehydrogenase inhibitor being tested in a clinical trial for the treatment of myeloid malignancies and COVID-19.
- | decitabine / Generic mfg.
Journal: DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes. (Pubmed Central) - May 15, 2021
Our results indicate that the DHODH inhibitor PTC299 suppresses the growth of MDS cells and acts in a synergistic manner with decitabine. This combination therapy may be a new therapeutic option for the treatment of MDS.
- emvododstat (PTC299) / PTC Therap
[VIRTUAL] The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines Implicated in COVID-19 Disease and Is Currently Being Evaluated in the Multinational FITE19 Phase 2/3 Clinical Trial in Hospitalized Patients (Poster Hall) - May 9, 2021 - Abstract #WMF2021WMF_970;
P2/3
PTC299 is being studied in the FITE19 Phase 2/3 clinical trial for the treatment of COVID-19 (Clinicaltrials.gov NCT04439071). The FITE19 trial will enroll 380 patients globally, with a primary endpoint of time from randomization to respiratory improvement.
- | emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Feb 12, 2021
P1b, N=39, Recruiting, Sponsor: PTC Therapeutics
The FITE19 trial will enroll 380 patients globally, with a primary endpoint of time from randomization to respiratory improvement. Trial completion date: Dec 2020 --> Jun 2021 | Trial primary completion date: Nov 2020 --> May 2021
- |||| emvododstat (PTC299) / PTC Therap
Trial completion date, Trial primary completion date: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Jan 11, 2021
P2/3, N=380, Recruiting, Sponsor: PTC Therapeutics
Trial completion date: Dec 2020 --> Jun 2021 | Trial primary completion date: Nov 2020 --> May 2021 Trial completion date: Jan 2021 --> Jul 2021 | Trial primary completion date: Jan 2021 --> Jul 2021
- | emvododstat (PTC299) / PTC Therap
Journal: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines. (Pubmed Central) - Jan 5, 2021
Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17 F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19.
- PTC299 / PTC Therap
[VIRTUAL] The Novel Dihydroorotate Dehydrogenase (DHODH) Inhibitor PTC299 Inhibit De Novo Pyrimidine Synthesis with Broad Anti-Leukemic Activity Against Acute Myeloid Leukemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1935;
Aim: We investigated the pre-clinical activity of PTC299 against AML in primary AML blasts and cytarabine-resistant cell lines. PTC299 is a novel dihydroorotate dehydrogenase (DHODH) inhibitor that triggers differentiation, apoptosis and/or inhibition of proliferation in AML and is being tested in a clinical trials for the treatment of acute myeloid malignancies.
- |||||| emvododstat (PTC299) / PTC Therap
Enrollment open: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Jul 21, 2020
P2/3, N=380, Recruiting, Sponsor: PTC Therapeutics
PTC299 is a novel dihydroorotate dehydrogenase (DHODH) inhibitor that triggers differentiation, apoptosis and/or inhibition of proliferation in AML and is being tested in a clinical trials for the treatment of acute myeloid malignancies. Not yet recruiting --> Recruiting
- | emvododstat (PTC299) / PTC Therap
Trial primary completion date: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Jul 7, 2020
P1b, N=39, Recruiting, Sponsor: PTC Therapeutics
Not yet recruiting --> Recruiting Trial primary completion date: May 2020 --> Nov 2020
- |||||||||| emvododstat (PTC299) / PTC Therap
New P2/3 trial: FITE19: A Study to Evaluate Efficacy and Safety of PTC299 (Emvododstat) in Hospitalized Participants With Coronavirus (COVID-19) (clinicaltrials.gov) - Jun 18, 2020
P2/3, N=380, Not yet recruiting, Sponsor: PTC Therapeutics
- || emvododstat (PTC299) / PTC Therap
Enrollment change: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Jan 15, 2020
P1b, N=36, Recruiting, Sponsor: PTC Therapeutics
Trial primary completion date: May 2020 --> Nov 2020 N=18 --> 36
- | PTC299 / PTC Therapeutics
Journal: Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties. (Pubmed Central) - Nov 28, 2019
Archived serum samples from patients treated with PTC299 demonstrated increased levels of dihydroorotate, the substrate of DHODH, indicating target engagement in patients. PTC299 has advantages over previously reported DHODH inhibitors, including greater potency, good oral bioavailability and lack of off-target kinase inhibition and myelosuppression, and thus may be useful for the targeted treatment of hematologic malignancies.
- Targeted Treatment and Survival Following Relapse after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and MDS in the Contemporary Era (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6321;
Targeted agents were used only in a minority of post-alloHCT relapses likely due to the combination of pt status, absence of the target mutation, the agents’ availability, and other factors . Pts who developed grade II-IV acute GVHD and had shorter “disease-free” duration from unrelated or haploidentical donor grafts had the significantly shorter survival following relapse .
- |||| emvododstat (PTC299) / PTC Therap
Phase classification, Trial termination, Metastases: PTC299 for Treatment of Advanced Cancer (clinicaltrials.gov) - May 10, 2019
P1b, N=76, Terminated, Sponsor: PTC Therapeutics
Pts who developed grade II-IV acute GVHD and had shorter “disease-free” duration from unrelated or haploidentical donor grafts had the significantly shorter survival following relapse . Phase classification: P1 --> P1b | Suspended --> Terminated
- || emvododstat (PTC299) / PTC Therap
Enrollment change: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Mar 29, 2019
P1b, N=18, Recruiting, Sponsor: PTC Therapeutics
Phase classification: P1 --> P1b | Suspended --> Terminated N=36 --> 18
- || emvododstat (PTC299) / PTC Therap
New P1 trial: Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias (clinicaltrials.gov) - Dec 3, 2018
P1b, N=36, Recruiting, Sponsor: PTC Therapeutics
- | emvododstat (PTC299) / PTC Therap
Enrollment change, Trial termination: PTC299 for Treatment of Neurofibromatosis Type 2 (clinicaltrials.gov) - Aug 28, 2018
P2, N=11, Terminated, Sponsor: PTC Therapeutics
N=36 --> 18 N=25 --> 11 | Suspended --> Terminated
- | emvododstat (PTC299) / PTC Therap
Clinical, P1 data, PK/PD data, Journal: Phase 1 Study of Safety, Tolerability, and Pharmacokinetics of PTC299, an Inhibitor of Stress-Regulated Protein Translation. (Pubmed Central) - Jan 26, 2018
The target trough plasma concentration associated with preclinical efficacy was achieved within 7 days at doses of 0.6 mg/kg twice daily and above. These data demonstrate that PTC299 is orally bioavailable and well tolerated and support clinical evaluation of PTC299 in cancer, certain viral infections, or other diseases in which deregulation of translational control is a causal factor.
- | emvododstat (PTC299) / PTC Therap
Trial completion, Trial primary completion date: PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors (clinicaltrials.gov) - May 4, 2015
P1, N=28, Completed, Sponsor: Pediatric Brain Tumor Consortium
These data demonstrate that PTC299 is orally bioavailable and well tolerated and support clinical evaluation of PTC299 in cancer, certain viral infections, or other diseases in which deregulation of translational control is a causal factor. Suspended --> Completed | Trial primary completion date: May 2012 --> Jan 2015
- emvododstat (PTC299) / PTC Therap
Trial suspension: PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors (clinicaltrials.gov) - Apr 16, 2012
P1, N=30, Suspended, Sponsor: Pediatric Brain Tumor Consortium
Suspended --> Completed | Trial primary completion date: May 2012 --> Jan 2015 Recruiting --> Suspended
- emvododstat (PTC299) / PTC Therap
Trial suspension: PTC299 for Treatment of Neurofibromatosis Type 2 (clinicaltrials.gov) - Apr 5, 2012
P2, N=25, Suspended, Sponsor: PTC Therapeutics
Recruiting --> Suspended Active, not recruiting --> Suspended
- | emvododstat (PTC299) / PTC Therap
Trial suspension, Metastases: PTC299 for Treatment of Advanced Cancer (clinicaltrials.gov) - Apr 5, 2012
P1, N=76, Suspended, Sponsor: PTC Therapeutics
Active, not recruiting --> Suspended Recruiting --> Suspended
- | emvododstat (PTC299) / PTC Therap
Trial completion, Combination therapy, Monotherapy, Metastases: PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer (clinicaltrials.gov) - Apr 5, 2012
P1, N=36, Completed, Sponsor: PTC Therapeutics
Recruiting --> Suspended Active, not recruiting --> Completed