- |||||||||| Adasuve (staccato loxapine) / AOP Orphan Pharma, Teva, Ferrer International, Galen, Medivir
Journal: The Dichotomous Nature of AZ5104 (an EGFR Inhibitor) Towards RORγ and RORγT. (Pubmed Central) - Apr 23, 2020
We thus identified a compound acting as an agonist of RORγ that, due to the inhibition of downstream elements of EGFR (epidermal growth factor receptor) signaling, exerts different biological activity towards a Th17-specific isoform. Additionally, our results may be relevant in the future for the design of treatments targeting signaling pathways that inhibit Th17-related inflammation in certain autoimmune disorders.
- |||||||||| Daklinza (daclatasvir) / BMS
Journal: Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals. (Pubmed Central) - Apr 14, 2020
Additionally, our results may be relevant in the future for the design of treatments targeting signaling pathways that inhibit Th17-related inflammation in certain autoimmune disorders. The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
- |||||||||| Olysio (simeprevir) / J&J, Medivir, Daklinza (daclatasvir) / BMS
Clinical, P2 data, Journal: Simeprevir, daclatasvir, and sofosbuvir for hepatitis C virus-infected patients: Long-term follow-up results from the open-label, Phase II IMPACT study. (Pubmed Central) - Apr 11, 2020
P2
No new safety signals were identified. In the IMPACT study, virologic response to simeprevir, sofosbuvir, and daclatasvir was durable over 3 years (http://ClinicalTrials.gov number: NCT02262728).
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Clinical, Journal: Absolute Bioavailability of Osimertinib in Healthy Adults. (Pubmed Central) - Apr 11, 2020
P1
Oral osimertinib was well absorbed. Simultaneous IV and oral PK analysis proved useful for complete understanding of osimertinib PK and showed that the first-pass effect was minimal for osimertinib.
- |||||||||| birinapant (TL 32711) / Medivir
Clinical, Journal, CAR T-Cell Therapy: Antagonism of IAPs enhances CAR T cell efficacy. (Pubmed Central) - Apr 10, 2020
Here, we demonstrated that antagonizing the "inhibitor of apoptosis proteins" with the clinical smac-mimetic, birinapant, significantly enhanced the antitumor activity of CAR T cells in a tumor necrosis factor (TNF)-dependent manner...Using patient biopsy-derived tumoroids, we demonstrated the synergistic potential of combining CAR T-cell therapy with smac-mimetics. Taken together, we identified CAR T cell-derived TNF as a potent antitumor effector, which can be further harnessed by smac-mimetics.
- |||||||||| Copegus (ribavirin) / Bausch Health, Sovaldi (sofosbuvir) / Gilead
Journal: Tolerability of erythrocyte ribavirin triphosphate concentrations depends on the ITPA genotype. (Pubmed Central) - Mar 12, 2020
Different SOF-based regimens were effective with high SVR12 rates in a difficult-to-treat population, recurrent HCV post LDLT. The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.
- |||||||||| Adasuve (staccato loxapine) / AOP Orphan Pharma, Teva, Ferrer International, Galen, Medivir, Semprana (dihydroergotamine oral inhalation) / Allergan
Journal: The discovery and development of inhaled therapeutics for migraine. (Pubmed Central) - Mar 5, 2020
In phase 2 trials, inhaled prochlorperazine shows good pharmacokinetics and efficacy, in contrast to inhaled loxapine that did not provide encouraging results in terms of efficacy. The authors see the potential for the use of dihydroergotamine mesylate in clinical practice pending regulatory approval.
- |||||||||| birinapant (IGM-9427) / IGM Biosciences
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Combination therapy: KEYNOTE 163: Dose-escalation Study of Birinapant and Pembrolizumab in Solid Tumors (clinicaltrials.gov) - Mar 4, 2020
P1/2, N=42, Terminated,
Utilization of pre-consent to enroll patients in a randomized trial of treatments for acute agitation in the ED requires substantial resources and may not be feasible. N=135 --> 42 | Trial completion date: Jun 2021 --> Feb 2020 | Recruiting --> Terminated | Trial primary completion date: Jun 2021 --> Feb 2020; Based on a futility analysis, the data monitoring committee recommended to stop enrollment.
- |||||||||| [VIRTUAL] RESISTANCE ANALYSIS IN HCV-3–INFECTED PATIENTS WITHIN THE ITALIAN NETWORK VIRONET-C ([VIRTUAL]) - Mar 2, 2020 - Abstract #CROI2020CROI_897;
Moreover, 14.8% of pts were treated with suboptimal regimens for GT3: 3DRBV (Paritaprevir/r+Ombitasvir+Dasabuvir, N=15), SOF+Simeprevir (N=1) or SOF/ Ledipasvir (LDV)+RBV (N=4)...The presence of natural NS5A RAS before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.
- |||||||||| Adasuve (staccato loxapine) / AOP Orphan Pharma, Teva, Ferrer International, Galen, Medivir
[VIRTUAL] Inhaled Loxapine in Agitated Psychosis: An Alternative to Coercive Measures (All Screens in Poster Area) - Feb 20, 2020 - Abstract #EPA2020EPA_2218;
Furthermore, QOL information may promote decision-making for treatment, leading to effective treatment. This study suggests that the use of inhaled loxapine in APPpatients otherwise prescribed mechanical restriction may be a useful alternative measure to avoid actual implementation of such coercive measure.
- |||||||||| Daklinza (daclatasvir) / BMS, Sovaldi (sofosbuvir) / Gilead
Journal: A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens. (Pubmed Central) - Jan 15, 2020
Although a virologic breakthrough occurred after an intermittent treatment regimen at the low fixed dose, the high fixed dose cured HCV-positive Huh7.5 cells with intermittent treatment. In conclusion, HCV is persistently present below detectable levels in HCV-infected Huh7.5 cells for a long time after treatment, and a shortened therapy duration is associated with an increased risk of virologic relapse, but virologic relapse or breakthrough might be avoided by treatment with a combination of more highly effective DAAs.
- |||||||||| Adasuve (staccato loxapine) / AOP Orphan Pharma, Teva, Ferrer International, Galen, Medivir, lorazepam / Generic mfg., haloperidol / Generic mfg.
Clinical, Journal: Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation. (Pubmed Central) - Dec 21, 2019
We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, birinapant (TL 32711) / Medivir
Journal: Sensitization of glioblastoma cells to TRAIL-induced apoptosis by IAP- and Bcl-2 antagonism. (Pubmed Central) - Dec 21, 2019
These findings were further corroborated in experiments with a translationally relevant hexavalent TRAIL variant. Our study therefore demonstrates that a high caspase-8/Bid signature is associated with synergistic TRAIL/TL32711-induced apoptosis in GBM cells and outlines Bcl-2 antagonism as a highly potent intervention to sensitize highly TRAIL-resistant GBM cells to TRAIL/TL32711 combination treatment.
- |||||||||| Daklinza (daclatasvir) / BMS
Clinical, Retrospective data, Journal, Heterogeneity: Efficacy, Safety, and Predictors of Direct-acting antivirals in Hepatitis C Virus Patients with Heterogeneous Liver Diseases. (Pubmed Central) - Dec 19, 2019
Model-for-End-Liver-Disease score <10 and alanine aminotransferase ≤20 U/L at week 8 of therapy proved positive predictors of sustained virological response. Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virologicalresponse.
- |||||||||| remetinostat (SHP-141) / Medivir
Enrollment open: Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) (clinicaltrials.gov) - Dec 9, 2019
P2, N=30, Recruiting,
Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virologicalresponse. Not yet recruiting --> Recruiting
- |||||||||| pibrentasvir (ABT-530) / AbbVie, Technivie (ombitasvir/paritaprevir/ritonavir) / AbbVie, glecaprevir (ABT-493) / AbbVie
Clinical, Journal, Real-World Evidence: Direct-Acting Antivirals for Hepatitis C: Predictors of Early Discontinuation in the Real World. (Pubmed Central) - Dec 6, 2019
These real-world data confirm low rates of early discontinuation in users of second-generation DAAs. Future research focusing on socio-economic and sex/gender issues may help further optimize care for patients with HCV.
- |||||||||| Copegus (ribavirin) / Bausch Health, Technivie (ombitasvir/paritaprevir/ritonavir) / AbbVie
Clinical, Journal, Real-World Evidence: Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in real world hepatitis C patients. (Pubmed Central) - Dec 6, 2019
Future research focusing on socio-economic and sex/gender issues may help further optimize care for patients with HCV. In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV is highly effective and tolerable and results in better mental and physical health following treatment.
- |||||||||| birinapant (TL 32711) / Medivir, AT-406 / Debiopharm, Ascenta, alisertib (MLN8237) / Takeda
Review, Journal, IO Biomarker: Therapeutic Inducers of Apoptosis in Ovarian Cancer. (Pubmed Central) - Nov 29, 2019
Several drugs in our review are undergoing clinical trials, for example, birinapant, DEBIO-1143, Alisertib, and other small molecules are in preclinical investigations showing promising results in combination with chemotherapy. Molecules that exhibit better efficacy in the treatment of chemo-resistant cancer cells are of interest but require more extensive preclinical and clinical evaluation.
- |||||||||| Mekinist (trametinib) / Novartis, Trintellix (vortioxetine) / Lundbeck, Takeda, Olysio (simeprevir) / J&J, Medivir
Clinical, Journal: Automatic extraction of quantitative data from ClinicalTrials.gov to conduct meta-analyses. (Pubmed Central) - Nov 23, 2019
EXACT (http://bio-nlp.org/EXACT) automatically and accurately extracted data elements from ClinicalTrials.gov and thus reduced time in data extraction. The ClinicalTrials.gov data reproduced most meta-analysis results in our study, but this conclusion needs further validation.
- |||||||||| birinapant (TL 32711) / Medivir, entinostat (SNDX-275) / Kyowa Hakko Kirin, Syndax
Journal: Cytoplasmic FLIP(S) and nuclear FLIP(L) mediate resistance of castrate-resistant prostate cancer to apoptosis induced by IAP antagonists. (Pubmed Central) - Nov 19, 2019
While the cytoplasmic pool of FLIP(L) was highly stable, the nuclear pool was more labile and regulated by the Class-I HDAC target Ku70, which we have previously shown regulates FLIP stability. The efficacy of IAP antagonist (TL32711) and Entinostat combination and their effects on cIAP1 and FLIP respectively were confirmed in vivo, highlighting the therapeutic potential for targeting IAPs and FLIP in proinflammatory CRPC.
- |||||||||| Sovaldi (sofosbuvir) / Gilead
Journal: Improvement in Waldenström's Macroglobulinemia after Successful Treatment of HCV with Direct-acting Antivirals. (Pubmed Central) - Nov 19, 2019
The recent advent of direct acting antivirals (DAAs) in the therapeutic armamentarium of HCV infection made possible treatment of patients with advanced liver disease. Here we report on a rare association of a cirrhotic patient with HCV and Waldenström's Macroglobulinemia with severe cryoglobulinemia, who had already failed an interferon-based antiviral regimen, whose haematologic disease was ameliorated by HCV eradication following treatment with sofosbuvir and simeprevir with ribavirin, and where successful treatment was accompanied also by consistent improvement in liver function and parameters of portal hypertension.
- |||||||||| fluorouracil / generics
Development of a proteomics-based predictor for targeted use of IAP antagonists in colorectal cancer () - Nov 5, 2019 - Abstract #NCRI2019NCRI_487;
However, CRIS-D and E cell lines responded well to FOLFOX+TL32711 co-treatment in the presence of TNFa. Although no correlations were observed between expression of any individual apoptotic protein and response to TL32711, we identified that the ratio of caspase-8, and its regulator, FLIP(L), was significantly correlated with sensitivity to TL32711+TNFa(r2= 0.46, p=0.02).
- |||||||||| Adasuve (staccato loxapine) / AOP Orphan Pharma, Teva, Ferrer International, Galen, Medivir
Trial completion date, Trial primary completion date: Phase IV to Evaluate the Safety of Self-administered ADASUVE (clinicaltrials.gov) - Oct 4, 2019
P4, N=500, Recruiting,
Close observation and longer follow-up studies, as well as, deeper investigations of the immune system are needed to better understand the underlying mechanism of Cryovas relapse after HCV viral eradication Trial completion date: Dec 2019 --> Sep 2020 | Trial primary completion date: Aug 2019 --> Mar 2020
- |||||||||| velpatasvir (GS-5816) / Gilead, voxilaprevir (GS-9857) / Gilead, Daklinza (daclatasvir) / BMS
HAS REAL LIFE EFFICACY OF SOFOSBUVIR-BASED REGIMENS CHANGED OVER TIME? FINDINGS FROM THE ANRS CO22 HEPATHER COHORT (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_2194;
P=N/A
In May 2018, 8278 patients with a least a 12 weeks post-treatmentfollow-uphad been treated with sofosbuvirin combination for 12 weeks with Ribavirin (RBV)(n =342, median date of prescription April 2014), Simeprevir (n=1033, October 2014, 14.5% with RBV and 8.8/4.7% for 24 weeks for cirrhotic/non cirrhotic patients), Daclatasvir (n=2755, January 2015, 30.4% with RBV and 64.5/27.4% for 24 weeks for cirrhotic/non cirrhotic patients), Ledipasvir (n=3526, November 2015, 50.3% with RBV and 16.0/2.8% for 24 weeks for cirrhotic/non cirrhotic patients), Velpatasvir (n=583, September 2017) and Velpatasvir+Voxilaprevir (n =39 for DAA failures, April 2018). In this large prospective cohort of French patients treated for HCV by a sofosbuvir- including regimen, SVR12 rates was greater than 95% in most of patients and did not significantly changed over time with the prioritization of the DAA combinations.
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