- |||||||||| Orkambi (lumacaftor/ivacaftor) / Vertex
Journal: Restoring CFTR function with Orkambi decreases the severity of alcohol-induced acute pancreatitis. (Pubmed Central) - Nov 19, 2024
CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol-induced pancreatitis. CFTR modulators present a novel option in the pharmacotherapy of alcohol-induced pancreatitis by enhancing pancreatic functions or preventing recurrence.
- |||||||||| tezacaftor (VX-661) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
Review, Journal: Precision medicine advances in cystic fibrosis: Exploring genetic pathways for targeted therapies. (Pubmed Central) - Nov 18, 2024
As research evolves, these advances can improve patient outcomes while minimizing adverse effects. Ethical considerations and regulatory challenges remain critical as personalized medicine advances, ensuring equitable access and the long-term effectiveness of these innovative therapies.
- |||||||||| suzetrigine (VX-548) / Vertex, VX-150 / Vertex
Journal: State-dependent inhibition of Nav1.8 channels by VX-150 and VX-548. (Pubmed Central) - Nov 18, 2024
This work describes the potency, selectivity, and state-dependent characteristics of inhibition of Nav1.8 channels by VX-150 and VX-548, compounds that have recently shown efficacy for relief of pain in clinical trials but whose mechanism of interaction with channels has not been described. The results show that the compounds share an unusual property whereby inhibition is relieved by depolarization, demonstrating a state-dependence different than most sodium channel inhibitors.
- |||||||||| suzetrigine (VX-548) / Vertex
Review, Journal: VX-548 in the treatment of acute pain. (Pubmed Central) - Nov 18, 2024
The results show that the compounds share an unusual property whereby inhibition is relieved by depolarization, demonstrating a state-dependence different than most sodium channel inhibitors. However, the safety of prolonged VX-548 administration is uncertain; a Phase II trial of patients with diabetic neuropathy who received high-dose VX-548 over 12
- |||||||||| Kalydeco (ivacaftor) / Vertex, icenticaftor (QBW251) / Novartis
Clinical data, Retrospective data, Review, Journal: Effects of cystic fibrosis transmembrane conductance regulator potentiators on clinical outcomes of chronic obstructive pulmonary disease: a systematic review and meta-analysis. (Pubmed Central) - Nov 18, 2024
George's Respiratory Questionnaire (SGRQ) score or acute exacerbation times, with low-to-moderate quality evidence.Review registration PROSPERO Identifier: CRD42024538708. Our meta-analysis demonstrated CFTR-potentiators' potential efficacy in increasing FEV1, decreasing sweat chloride and fibrinogen levels, despite limited impacts on FEV1% predicted, FVC, CAT score, SGRQ score and acute exacerbations, underscoring the necessity for future research to evaluate its effects on mucus hypersecretion, acute exacerbations, hospitalizations and mortality in COPD management.Review registration PROSPERO Identifier: CRD42024538708.
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Review, Journal, Gene therapy: Gene therapy and gene editing strategies in inherited blood disorders. (Pubmed Central) - Nov 17, 2024
Erythroid regulatory factor BCL11A offers the most promising therapeutic target for ?-hemoglobinopathies, and reduction of its expression using the commercialized gene therapy product Casgevy has been approved for use in the UK and USA in 2023...Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future.
- |||||||||| elexacaftor (VX-445) / Vertex, Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
Journal: Sweat test evolution in cystic fibrosis patients treated with Elexacaftor/Tezacaftor/Ivacaftor (Pubmed Central) - Nov 17, 2024
Under highly effective modulators such as the combination of Elexacaftor, Tezacaftor and Ivacaftor (ETI), the Cl- level in sweat significantly improves, as shown in our cohort of patients when ETI was introduced. In addition to its role in the diagnosis of the disease, the sweat test is also important for individual clinical trials (n-of-1) in patients not eligible for ETI and for newborn screening for cystic fibrosis.
- |||||||||| carboplatin / Generic mfg., gemcitabine / Generic mfg.
Trial completion date, Trial primary completion date, Metastases: Carboplatin, Gemcitabine Hydrochloride, and Berzosertib in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - Nov 15, 2024
P1, N=31, Active, not recruiting,
This underscores the need for uninterrupted continuation of modulatory treatment and for improved policies to ensure equitable access to treatment. Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025
- |||||||||| berzosertib (M6620) / EMD Serono
Trial completion date, Trial primary completion date, Combination therapy: Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer (clinicaltrials.gov) - Nov 15, 2024
P1, N=42, Active, not recruiting,
Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025 Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Journal: Beyond the traditional distinctions of genome editing: evaluating a vulnerability framework. (Pubmed Central) - Nov 14, 2024
Even with new somatic treatments that are generally lauded, exemplified with the case of Casgevy, many issues still arise - such as cost and access, particularly salient on a global level...In this paper, we will highlight the limits of the two distinctions in terms of moving from questions of "should a technology be used" to "how should a technology be used." We argue that an additional focus on vulnerability and marginalization can be useful to support the attempt to better prioritize which interventions should be permitted or prohibited. We show how this can better dovetail with calls for effective (global) governance and reasonable consensus by focusing on the most urgent issues and developing policy accordingly, while leaving aside more abstract issues for further discussion.
- |||||||||| VX-993 oral / Vertex
Enrollment open: A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy (clinicaltrials.gov) - Nov 14, 2024
P2, N=355, Recruiting,
Over the first 18 months of ETI usage, the percentage of patients with these symptoms decreased, suggesting that the percentage of patients experiencing severe symptoms of depression and anxiety may decrease with ongoing use of ETI. Not yet recruiting --> Recruiting
- |||||||||| berzosertib (M6620) / EMD Serono, Leukeran (chlorambucil) / GSK
Journal: Targeting ATR Kinase as a Strategy for Canine Lymphoma and Leukaemia Treatment. (Pubmed Central) - Nov 13, 2024
Berzosertib also acted synergistically with chlorambucil, probably by preventing DNA damage repair as a consequence of S-phase arrest abrogation. In conclusion, ATR inhibition may provide a new therapeutic option for the treatment of canine lymphomas and leukaemias, but further studies are required to determine potential biomarkers of their susceptibility.
- |||||||||| Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
Review, Journal: The role of CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health. (Pubmed Central) - Nov 13, 2024
In the past decade, highly effective CFTR modulator therapies, including elexacaftor-tezacaftor-ivacaftor, have revolutionised CF management by correcting the underlying molecular defect to improve patient outcomes and life expectancy...This review summarises the possible role of CFTR in the developing eye, and the potential impact of CFTR on eye function and vision later in life. This information provides a framework for understanding the use and possible effects of CFTR-modulating therapeutics in the context of eye health, including the potential to leverage the eye for non-invasive and accessible diagnostic and monitoring capabilities in patients with CF.
- |||||||||| Lyfgenia (lovotibeglogene autotemcel) / bluebird bio, Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Multi-Disciplinary Care Model for Transition and Re-Transition after Gene Therapy in Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4476;
This led to the Food and Drug Administration (FDA) approval of the lentiviral-based gene addition product (lovotibeglogene autotemcel) and CRISPR-Cas9 based gene editing product (exagamglogene autotemcel) for patients with SCD above 12 years of age. As newer therapies are developed and approved for transformative SCD care, development of a transitional model with early engagement of an interdisciplinary team is critical for empowering sickle cell warriors and for their successful transition back into the community.
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates, OTQ923 / Novartis, Intellia Therap
Rheological Comparison of Red Cells from Individuals with SCD Treated with Gene Therapy, Haploidentical Transplantation or Hydroxyurea (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4394;
P1, P1/2,
We observed a wide range of red cell function values in the GT group, suggesting that with appropriate clinical correlations, these tests can help compare different GT strategies by assessing the degree of red cell correction achieved by each one. We found that the RBC quality and function of HU was comparable to GT, when samples are selected from individuals having a HbF/functional hemoglobin response comparable to that that of individuals post GT.
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Durable Clinical Benefits with Exagamglogene Autotemcel for Severe Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4392;
All participants had durable increases in Hb and HbF levels and stable allelic editing; clinically meaningful improvements were also seen in hemolysis markers and QOL measures. The safety profile of exa-cel remains consistent with myeloablative busulfan conditioning and autologous transplantation.
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Durable Clinical Benefits with Exagamglogene Autotemcel for Transfusion-Dependent ?-Thalassemia (Room 30 (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_1800;
Durable increases in Hb and HbF levels and stable allelic editing were observed. Additional efficacy was seen with improvement in iron overload and ability to stop iron removal therapy, as well as clinically meaningful improvements in QOL.
- |||||||||| Monjuvi (tafasitamab-cxix) / Incyte, belnacasan (VX-765) / Vertex
Caspase-1 Inhibition Ameliorates CAR T-Cell Apoptosis and Tumor Cell Pyroptosis to Enhance the Efficacy and Safety of CAR T-Cell Therapy (Room 6CF (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_1604;
costimulated) cells significantly ameliorated CAR T-cell apoptosis and tumor cell pyroptosis, improving CAR T safety and efficacy (PMID: 37879074)...Mice were treated 12 days later with cyclophosphamide (300 mg/kg, ip) and 24 hours after mice were imaged and randomized to receive 1 x 107, 1) untransduced T cell control (UTD), 2) mCART19 + vehicle control, or 3) mCART19 + VX765 (25 mg/kg)...VX765 also reduced tumor cell pyroptosis and CRS incidence without impacting CAR T anti-tumor activity in vivo. Given the favorable preclinical outcomes and existing clinical data on VX765, this approach holds substantial translational potential for enhancing the safety and efficacy of CAR T-cell therapy in patients with large B-cell lymphoma.
- |||||||||| berzosertib (M6620) / EMD Serono
Combination DDR inhibition with immunotherapy approaches for effectively enhancing tumor control in tumor-bearing mice model () - Nov 5, 2024 - Abstract #APSR2024APSR_101;
Given the favorable preclinical outcomes and existing clinical data on VX765, this approach holds substantial translational potential for enhancing the safety and efficacy of CAR T-cell therapy in patients with large B-cell lymphoma. Taken together, DDR inhibition displays the board therapeutic prospects and holds the promising potential in modifying the proportion of immune cells, thereby reinforcing the tumor immune microenvironment in combination with immunotherapy in non-small cell lung cancer.
- |||||||||| Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
Journal: Heightened mitochondrial respiration in CF cells is normalised by triple CFTR modulator therapy through mechanisms involving calcium. (Pubmed Central) - Nov 5, 2024
However, the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has resulted in a paradigm shift in nutritional status for many people with CF, with increase body mass index and reduction in the need for nutritional support...ETI decreased intracellular calcium levels in CF cells to the same extent as BAPTA-AM, highlighting the importance of calcium and chloride in mitochondrial respiration in CF. CF cell lines exhibit increased mitochondrial respiration, which can be downregulated by ETI therapy through mechanisms involving calcium.
- |||||||||| Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
An Update on the Utilization and Expenditure Associated With Cystic Fibrosis Targeted Therapies in Ireland () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_3333;
Neither ivacaftor nor lumacaftor/ivacaftor were considered cost-effective when subject to Health Technology Assessment (HTA). Tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor were not subjected to HTA prior to their reimbursement, due to the introduction of a
- |||||||||| Finding a Way for Patients to Access Gene Therapies () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_2243;
Canada and UK mainly use financial-based schemes built on simple price discounts. Australia and the US aim at implementing schemes whereby treatment cost payers incur corresponds to expected health outcome for a particular patient.
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Model-Projected Clinical Outcomes of Exagamglogene Autotemcel (exa-cel) in Patients With Transfusion-Dependent Beta-Thalassemia in Canada () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_1670;
In addition, our analysis shows the GRACE method would raise the WTP threshold, which, in the scenario presented, would alter the conclusion and recommendation on the cost?effectiveness of exa?cel. Model projections suggest exa-cel could substantially improve survival, lower the prevalence of TDT-related complications, and reduce disease burden in patients with TDT in Canada compared to treatment with SOC.
- |||||||||| Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
Journal, Surgery: Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis. (Pubmed Central) - Nov 1, 2024
Understanding how these factors impact response to treatment may improve care disparities among PwCF. In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.
- |||||||||| suzetrigine (VX-548) / Vertex
Enrollment open: Evaluation of Efficacy and Safety of Suzetrigine for Pain Associated With Diabetic Peripheral Neuropathy (clinicaltrials.gov) - Nov 1, 2024
P3, N=1100, Recruiting,
In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF. Not yet recruiting --> Recruiting
- |||||||||| Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates
Enrollment change, Trial completion date, Trial primary completion date: CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease (clinicaltrials.gov) - Oct 31, 2024
P2/3, N=63, Active, not recruiting,
The work provides mechanistic insights into the risk of DDIs between kinase inhibitors and anticoagulants, which can be used to avoid preventable DDIs in the clinic. N=45 --> 63 | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025
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