Cystic Fibrosis Treatment Report
www.CysticFibrosisTreatmentReport.com
https://www.cff.org/News/News-Archive/2020/FDA-Approves-Kalydeco-for-Infants-as-Young-as-4-Months/
FDA Approves Kalydeco for Infants as Young as 4 Months
The U.S. Food and Drug Administration has approved the use of Kalydeco® (ivacaftor) for infants with cystic fibrosis as young as four months who have certain mutations.
https://www.frontiersin.org/articles/10.3389/fphar.2020.01219/full
Front. Pharmacol., 13 August 2020 | https://doi.org/10.3389/fphar.2020.01219
CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis
https://clinicaltrials.gov/ct2/show/NCT04353817?recrs=abdf
https://clinicaltrials.gov/ct2/show/NCT04353817?recrs=abdf&type=Intr&cond=Cystic+Fibrosis&lupd_s=04%2F06%2F2020&lupd_d=14
Condition : Cystic Fibrosis
Interventions : Drug: ELX/TEZ/IVA; Drug: IVA; Other: Placebo
Sponsor : Vertex Pharmaceuticals Incorporated
Not yet recruiting
A Study Evaluating Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis and F/MF Genotypes
NCT04353817
Mon, 20 Apr 2020 12:00:00 EDT
Last Update Posted: 04/20/20 07:17AM
https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.24424
https://www.ncbi.nlm.nih.gov/pubmed/31237430?dopt=Abstract
Related Articles
Effectivenesss of ivacaftor in severe cystic fibrosis patients and non-G551D gating mutations.
Pediatr Pulmonol. 2019 Jun 25;:
Authors: Salvatore D, Carnovale V, Iacotucci P, Braggion C, Castellani C, Cimino G, Colangelo C, Francalanci M, Leonetti G, Lucidi V, Manca A, Vitullo P, Ferrara N
Abstract
BACKGROUND: Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined.
METHODS: Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV1 ] < 40%, or on lung transplant waiting list, or with a fast worsening trend of lung function). Data were collected for 1 year before and 1 year after ivacaftor commencement. RESULTS: Thirteen patients received ivacaftor for a median of 320 days. Mean (SD) ppFEV1 increased from 35.1% (14.3%) before treatment to 46.6% (18.8%) after 12 months of treatment (absolute increase 11.5%, relative increase 32.8%). Mean distance of the 6-minute walking test improved significantly, from 535.1 m before to 611.6 m after 12 months of treatment (P = .002). The number of pulmonary exacerbations decreased significantly, from 57 during the year before ivacaftor to 28 in the year following ivacaftor (P = .0048). Five of the 13 patients (38.5%) had no exacerbations during the 12 months after starting ivacaftor. Median weight increased significantly, from 52.7 kg to 55.6 kg (P = .0031). Mean (SD) sweat chloride concentration decreased significantly, from 99.5 (22.8) mmol/L to 39.3 (15.8) mmol/L (P < .0001). No safety concerns were registered. CONCLUSIONS: Ivacaftor was safe and effective in patients with CF with severe lung disease and non-G551D gating mutations. PMID: 31237430 [PubMed - as supplied by publisher] PubMed:31237430
https://elifesciences.org/articles/46450
https://www.ncbi.nlm.nih.gov/pubmed/31205003?dopt=Abstract
Cystic fibrosis drug ivacaftor stimulates CFTR channels at picomolar concentrations.
Elife. 2019 Jun 17;8:
Authors: Csanády L, Töröcsik B
Abstract
The devastating inherited disease cystic fibrosis (CF) is caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel. The recent approval of the CFTR potentiator drug ivacaftor (Vx-770) for the treatment of CF patients has marked the advent of causative CF therapy. Currently, thousands of patients are being treated with the drug, and its molecular mechanism of action is under intensive investigation. Here we determine the solubility profile and true stimulatory potency of Vx-770 towards wild-type (WT) and mutant human CFTR channels in cell-free patches of membrane. We find that its aqueous solubility is ~200-fold lower (~60 nanomolar), whereas the potency of its stimulatory effect is >100-fold higher, than reported, and is unexpectedly fully reversible. Strong, but greatly delayed, channel activation by picomolar Vx-770 identifies multiple sequential slow steps in the activation pathway. These findings provide solid guidelines for the design of in vitro studies using Vx-770.
PMID: 31205003 [PubMed – as supplied by publisher]
PubMed:31205003
https://investors.vrtx.com/news-releases/news-release-details/vertex-selects-triple-combination-regimen-vx-445-tezacaftor-and
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004827-29
EudraCT Number: 2014-004827-29
Sponsor Protocol Number: VX14-661-110
Sponsor Name: Vertex Pharmaceuticals Incorporated
Start Date: 2015-09-01
Medical condition: Cystic Fibrosis
Disease:
Version: 18.0
SOC Term: 10010331 – Congenital, familial and genetic disorders
Classification Code: 10011762
Term: Cystic fibrosis
Level: PT
Population Age: Adolescents, Under 18, Adults
Gender: Male, Female
Trial Protocol: IT (Ongoing), IE (Ongoing), GB (Ongoing), BE (Ongoing), SE (Ongoing), AT (Completed), DK (Ongoing), NL (Ongoing), DE (Ongoing), ES (Completed)
A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long term Treatment With VX 661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, …
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004827-29
Last Update Posted: 05/06/19 11:34AM
https://www.biospace.com/article/releases/fda-approves-kalydeco-ivacaftor-as-first-and-only-cftr-modulator-to-treat-eligible-infants-with-cf-as-early-as-six-months-of-age/
https://www.tandfonline.com/doi/abs/10.1080/17476348.2019.1602040?journalCode=ierx20
https://www.ncbi.nlm.nih.gov/pubmed/30929526?dopt=Abstract
Related Articles
Safety and efficacy of treatment with lumacaftor in combination with ivacaftor in younger patients with cystic fibrosis.
Expert Rev Respir Med. 2019 Mar 30;:
Authors: Cheng PC, Alexiou S, Rubenstein RC
Abstract
INTRODUCTION: Cystic fibrosis (CF) is the most common autosomal recessive disorder affecting approximately 70,000 people worldwide. The lack of functional cystic fibrosis transmembrane conductance regulator (CFTR) causes dysregulation of epithelial fluid transport in the lungs, gastrointestinal tract, and sweat glands. Areas covered: The most common disease-causing CFTR mutation, F508del, is present in nearly 75% of those affected and results in a defective protein. Therapies to improve the function of this mutant protein have the promise to reduce morbidity and mortality in the majority of patients with CF. The combination of lumacaftor, which corrects the aberrant intracellular trafficking of F508del, and ivacaftor, which potentiates CFTR function, is known as OrkambiTM, and is the first drug approved for the treatment of cystic fibrosis (CF) in patients who are homozygous for F508del. OrkambiTM is currently approved for use in children aged 2 and older based on recent data from open-label Phase 3 clinical safety studies. In older patients, treatment with lumacaftor/ivacaftor is associated with a modest, statistically significant improvement in lung function and reduced pulmonary exacerbations in placebo-controlled trials; these findings are also observed in Phase IV observational studies. While severe side effects are rare, chest tightness, elevation of transaminases, and cataracts have been reported and recommendations for monitoring have been established. Expert opinion: OrkambiTM somewhat improves clinical outcomes for people with CF who are homozygous for the F508del mutation, and does so with a reasonable safety profile. This therapy represents a major advance in the therapy for CF, but further advances are needed, perhaps with addition of a third agent to this combination small molecule therapy, in order to expand both the targeted population and beneficial effects.
PMID: 30929526 [PubMed – as supplied by publisher]
PubMed:30929526
