scholarly journals A Comparative Analysis of Pricing and Reimbursement of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Europe

2021 ◽  
Vol 12 ◽  
Author(s):  
Khadidja Abdallah ◽  
Kris De Boeck ◽  
Marc Dooms ◽  
Steven Simoens
Keyword(s):  
Cystic Fibrosis ◽  
Budget Impact ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Daily Dose ◽  
Managed Entry Agreements ◽  
Pricing And Reimbursement ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators ◽  
List Prices

Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor), have substantially improved patients’ lives yet significantly burden healthcare budgets. This analysis aims to compare pricing and reimbursement of aforementioned cystic fibrosis medicines, across European countries.Methods: Clinical trial registries, national databases, health technology assessment reports and grey literature of Austria, Belgium, Denmark, France, Germany, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, the United Kingdom were consulted. Publicly available prices, reimbursement statuses, economic evaluations, budget impact analyses and managed entry agreements of CFTR modulators were examined. Results: In Belgium, lowest list prices were observed for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €417 per defined daily dose (DDD) and €372 per average daily dose (ADD), respectively. Whereas, Switzerland had the lowest price for Orkambi® (lumacaftor/ivacaftor) listed at €309 per DDD. Spain had the highest prices for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €850 per DDD and €761 per ADD, whereas Orkambi® (lumacaftor/ivacaftor) was most expensive in Poland at €983 per DDD. However, list prices were subject to confidential discounts and likely varied from actual costs. In all countries, these treatments were deemed not to be cost-effective. The annual budget impact of the CFTR modulators varied between countries and depended on factors such as local product prices, size of target population, scope of costs and discounting. However, all modulators were fully reimbursed in ten of the evaluated countries except for Sweden and Poland that, respectively, granted reimbursement to one and none of the therapies. Managed entry agreements were confidential but commonly adopted to address financial uncertainties.Conclusion: Discrepancies concerning prices, reimbursement and access were detected for Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor) across European countries.

scholarly journals Progress in precision medicine in cystic fibrosis: a focus on CFTR modulator therapy

Breathe ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. 210112
Author(s):  
Daniel H. Tewkesbury ◽  
Rebecca C. Robey ◽  
Peter J. Barry
Keyword(s):  
Cystic Fibrosis ◽  
Precision Medicine ◽  
Real World ◽  
Chloride Ion ◽  
Transmembrane Conductance Regulator ◽  
Therapeutic Approaches ◽  
Transmembrane Conductance ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

The genetic multisystem condition cystic fibrosis (CF) has seen a paradigm shift in therapeutic approaches within the past decade. Since the first clinical descriptions in the 1930s, treatment advances had focused on the downstream consequences of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel. The discovery of the gene that codes for CFTR and an understanding of the way in which different genetic mutations lead to disruption of normal CFTR function have led to the creation and subsequent licensing of drugs that target this process. This marks an important move towards precision medicine in CF and results from clinical trials and real-world clinical practice have been impressive. In this review we outline how CFTR modulator drugs restore function to the CFTR protein and the progress that is being made in this field. We also describe the real-world impact of CFTR modulators on both pulmonary and multisystem complications of CF and what this will mean for the future of CF care.

scholarly journals Elexacaftor/tezacaftor/ivacaftor in an individual with cystic fibrosis caused by a N1303K CFTR variant and infected with Mycobacterium abscessus

2021 ◽  
Author(s):  
E. Elson ◽  
Paula Capel ◽  
Jessica Haynes ◽  
Stephanie Duehlmeyer ◽  
Michelle Fischer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mycobacterium Abscessus ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Protein Variants ◽  
Cftr Modulators ◽  
Clinical Stability

This report describes a case of a 15-year-old male with cystic fibrosis caused by N1303K and Q493X cystic fibrosis transmembrane conductance regulator (CFTR) protein variants. In this case, CFTR modulators including tezacaftor/ivacaftor and subsequently elexacaftor/tezacaftor/ivacaftor were utilized and resulted in clinical stability and improvement.

scholarly journals Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

2020 ◽  
Vol 34 (4) ◽  
pp. 573-580
Author(s):  
Saangyoung E. Lee ◽  
Zainab Farzal ◽  
M.Leigh Anne Daniels ◽  
Brian D. Thorp ◽  
Adam M. Zanation ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Respiratory Compromise ◽  
Basic Understanding ◽  
Epithelial Cultures ◽  
Cf Transmembrane Conductance Regulator ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators ◽  
Initial Results

Background Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.

Treating the Underlying Cystic Fibrosis Transmembrane Conductance Regulator Defect in Patients with Cystic Fibrosis

2019 ◽  
Vol 40 (06) ◽  
pp. 762-774 ◽  
Author(s):  
Senne Cuyx ◽  
Kris De Boeck
Keyword(s):  
Cystic Fibrosis ◽  
Significant Proportion ◽  
Real Life ◽  
Current Treatment ◽  
Detailed Knowledge ◽  
Transmembrane Conductance Regulator ◽  
Class Iii ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

AbstractDetailed knowledge of how mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disturb the trafficking or function of the CFTR protein and the use of high-throughput drug screens have allowed novel therapeutic strategies for cystic fibrosis (CF). The main goal of treatment is slowly but surely shifting from symptomatic management to targeting the underlying CFTR defect to halt disease progression and even to prevent occurrence of CF complications. CFTR potentiators for patients with class III mutations, mutation R117H (and in United States also for patients with specific residual function mutations) and the combination of a CFTR modulator plus a potentiator for patients homozygous for F508del, are the two classes of modulators that are in use in the clinic. Approval of these therapeutics has progressively expanded to include both younger patients and a wider range of CFTR mutations. For a significant proportion of patients with CF, current treatment is however still insufficient or unavailable.This review provides an overview of the clinical trial results and the real-life efficacy data of approved CFTR modulators. In addition, we discuss the entire pipeline of CFTR modulators: novel potentiators and correctors, amplifiers, stabilizers, and read-through agents. Furthermore, we discuss other strategies to improve CFTR function like nonsense-mediated decay inhibitors, modified transfer ribonucleic acids, antisense oligonucleotides, and genetic therapies.CFTR modulators are already changing the face of CF and the pipeline of new therapies continues to be exciting.

scholarly journals State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators and Triple-Combination Therapy

2021 ◽  
Vol 14 (9) ◽  
pp. 928
Author(s):  
Aniello Meoli ◽  
Valentina Fainardi ◽  
Michela Deolmi ◽  
Giulia Chiopris ◽  
Francesca Marinelli ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Young Children ◽  
Autosomal Recessive Disorder ◽  
Cftr Gene ◽  
Transmembrane Conductance Regulator ◽  
Inherited Disease ◽  
Transmembrane Conductance ◽  
Triple Combination Therapy ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.

scholarly journals New Therapies to Correct the Cystic Fibrosis Basic Defect

2021 ◽  
Vol 22 (12) ◽  
pp. 6193
Author(s):  
Christelle Bergeron ◽  
André M. Cantin
Keyword(s):  
Cystic Fibrosis ◽  
Rare Diseases ◽  
Current Knowledge ◽  
Apical Surface ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Disease Treatment ◽  
Basic Defect ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

Rare diseases affect 400 million individuals worldwide and cause significant morbidity and mortality. Finding solutions for rare diseases can be very challenging for physicians and researchers. Cystic fibrosis (CF), a genetic, autosomal recessive, multisystemic, life-limiting disease does not escape this sad reality. Despite phenomenal progress in our understanding of this disease, treatment remains difficult. Until recently, therapies for CF individuals were focused on symptom management. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its product, a protein present at the apical surface of epithelial cells regulating ion transport, allowed the scientific community to learn about the basic defect in CF and to study potential therapies targeting the dysfunctional protein. In the past few years, promising therapies with the goal to restore CFTR function became available and changed the lives of several CF patients. These medications, called CFTR modulators, aim to correct, potentialize, stabilize or amplify CFTR function. Furthermore, research is ongoing to develop other targeted therapies that could be more efficient and benefit a larger proportion of the CF community. The purpose of this review is to summarize our current knowledge of CF genetics and therapies restoring CFTR function, particularly CFTR modulators and gene therapy.

scholarly journals Review of CFTR Modulators 2020

2021 ◽  
Author(s):  
Danielle Goetz ◽  
Adrienne Savant
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Care ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Positive Effects ◽  
Fda Approval ◽  
Pediatric Pulmonology ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

CFTR (cystic fibrosis transmembrane conductance regulator) modulators are small molecules that directly change the CFTR protein, improving function of the CFTR chloride channel. Beginning in 2012 with the FDA approval of the first CFTR modulator, ivacaftor, this class of medication has had largely positive effects on many outcomes in people with cystic fibrosis (pwCF), including lung function, quality of life, and growth. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three-part Cystic Fibrosis (CF) Year in Review 2020 will focus on research on CFTR modulators. Subsequent parts of the CF year in review will cover pulmonary and infectious inflammatory aspects, and the multisystem effects of CF in the 2020 literature. The review focuses on articles from Pediatric Pulmonology, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.

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