CLINICAL TRIALS PROFILE FOR IVACAFTOR; LUMACAFTOR

All Clinical Trials for IVACAFTOR; LUMACAFTOR

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01225211 ↗	Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2010-10-01	The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.
NCT01768663 ↗	A Phase 1 Study to Examine the Drug-Drug Interaction of Ciprofloxacin, Itraconazole, and Rifampin on the Combination of Lumacaftor With Ivacaftor in Healthy Adult Subjects	Completed	Vertex Pharmaceuticals Incorporated	Phase 1	2013-01-01	The purpose of this study is to examine the drug-drug interaction effects of ciprofloxacin, itraconazole, and rifampin on the pharmacokinetics of lumacaftor in combination with ivacaftor as well as to evaluate the potential effects of lumacaftor in combination with ivacaftor on lung function.
NCT01807923 ↗	A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 3	2013-05-01	The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
NCT01807949 ↗	A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 3	2013-04-01	The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
NCT01888393 ↗	Study of Lumacaftor in Combination With Ivacaftor in Subjects With Moderate Hepatic Impairment and Healthy Subjects	Completed	Vertex Pharmaceuticals Incorporated	Phase 1	2013-06-01	This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of lumacaftor in combination with ivacaftor in subjects with moderate hepatic impairment.
NCT01897233 ↗	Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 3	2013-07-01	This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Clinical Trial Conditions for IVACAFTOR; LUMACAFTOR

Condition Name

Condition Name for IVACAFTOR; LUMACAFTOR
Intervention	Trials
Cystic Fibrosis	30
Healthy Volunteer	2
Cystic Fibrosis, Homozygous for the F508del CFTR Mutation	2
Diabetes	2

Condition MeSH

Condition MeSH for IVACAFTOR; LUMACAFTOR
Intervention	Trials
Cystic Fibrosis	33
Fibrosis	27
Lung Diseases	2
Disease Progression	1

Clinical Trial Locations for IVACAFTOR; LUMACAFTOR

Trials by Country

Trials by Country for IVACAFTOR; LUMACAFTOR
Location	Trials
United States	371
Canada	32
France	23
Germany	19
United Kingdom	19

Trials by US State

Trials by US State for IVACAFTOR; LUMACAFTOR
Location	Trials
Colorado	16
Missouri	16
California	15
Ohio	15
Massachusetts	15

Clinical Trial Progress for IVACAFTOR; LUMACAFTOR

Clinical Trial Phase

Clinical Trial Phase for IVACAFTOR; LUMACAFTOR
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	12
Phase 2	5

Clinical Trial Status

Clinical Trial Status for IVACAFTOR; LUMACAFTOR
Clinical Trial Phase	Trials
Completed	23
Recruiting	5
Terminated	3

Clinical Trial Sponsors for IVACAFTOR; LUMACAFTOR

Sponsor Name

Sponsor Name for IVACAFTOR; LUMACAFTOR
Sponsor	Trials
Vertex Pharmaceuticals Incorporated	21
Massachusetts General Hospital	2
Children's Hospital Medical Center, Cincinnati	2

Sponsor Type

Sponsor Type for IVACAFTOR; LUMACAFTOR
Sponsor	Trials
Industry	26
Other	15
NIH	1

IVACAFTOR; LUMACAFTOR Market Analysis and Financial Projection

Transforming Cystic Fibrosis Treatment: Updates on Ivacaftor and Lumacaftor

Introduction

Cystic fibrosis (CF) is a debilitating genetic disorder that affects the respiratory, digestive, and reproductive systems. The recent advancements in the treatment of CF, particularly with the drugs ivacaftor and lumacaftor, have marked a significant turning point in the management and potential long-term outcomes of the disease.

Clinical Trials: Ivacaftor and Lumacaftor Combination

Phase 3 Studies

The combination of ivacaftor (Kalydeco) and lumacaftor (VX-809), marketed as Orkambi, has shown promising results in Phase 3 clinical trials. These studies, conducted over 24 weeks, involved patients with two copies of the F508del mutation, the most common mutation in CF. The results indicated significant improvements in lung function, as measured by the absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline at Week 24[1][4].

Efficacy and Safety

The trials demonstrated that the combination therapy improved lung function and reduced the rate of pulmonary exacerbations. The pharmacokinetic interactions between ivacaftor and lumacaftor were closely monitored, showing that while there were significant effects on the plasma concentrations of both drugs, there was no increase in adverse events compared to either drug alone[3].

Long-Term Impact

Long-term studies, including a Phase 2 trial extended into an open-label treatment period, have shown that lumacaftor/ivacaftor treatment can modify early CF disease progression in children as young as 2 years old. These studies assessed endpoints such as chest MRI global score, weight-for-age, stature-for-age, and BMI-for-age, indicating positive effects on disease progression and growth parameters[5].

Mechanism of Action

Correcting the Defective CFTR Protein

Ivacaftor acts as a CFTR potentiator, increasing the fraction of time the CFTR channel is open, thereby enhancing chloride secretion. Lumacaftor, on the other hand, corrects the defective CFTR protein by improving its maturation, trafficking, and cell surface stability. When combined, these drugs synergistically increase CFTR-mediated chloride secretion, leading to improved lung function and reduced disease severity[3].

Market Analysis and Projections

Market Growth

The cystic fibrosis market is projected to experience significant growth, driven largely by the introduction of novel CFTR modulators like Orkambi. According to GlobalData, the market is expected to grow from $2.1 billion in 2015 to approximately $7.6 billion by 2025, representing a compound annual growth rate of 13.6 percent[2].

Key Drivers

The introduction of Orkambi in 2015 was a major driver of this growth. The drug's approval and subsequent adoption have significantly improved treatment options for patients with the F508del mutation, which accounts for nearly 50% of the CF population. Additional high-priced, disease-modifying CFTR modulators are expected to further fuel market growth during the forecast period[2].

Impact on Patient Care

Improved Lung Function

The combination of ivacaftor and lumacaftor has been shown to improve lung function, reduce pulmonary exacerbations, and enhance the overall quality of life for patients with CF. This is particularly significant for patients with the F508del mutation, who previously had limited treatment options[1][4].

Early Intervention

Studies have indicated that early intervention with these drugs, even in children as young as 2 years old, can modify the progression of CF disease. This early treatment can potentially delay the onset of severe lung disease and improve long-term outcomes[5].

Collaboration and Innovation

Cystic Fibrosis Foundation's Role

The Cystic Fibrosis Foundation has played a crucial role in the development of these drugs through its innovative venture philanthropy model. The Foundation has invested millions of dollars in research, including $75 million in the development of ivacaftor and lumacaftor. This collaborative effort with Vertex Pharmaceuticals and other biotech companies has accelerated the development of effective treatments for CF[1].

Future Developments

The Foundation continues to pursue the development of other promising compounds that address the basic defect in CF. Collaborations with leading biotech and pharmaceutical companies, such as Pfizer and Genzyme, are driving innovative research strategies that could speed the development of therapies for all people with CF, including those with rare mutations[1].

Key Takeaways

• Clinical Efficacy: The combination of ivacaftor and lumacaftor has shown significant improvements in lung function and disease progression in patients with the F508del mutation.
• Market Growth: The cystic fibrosis market is projected to grow substantially, driven by the introduction of novel CFTR modulators.
• Early Intervention: Early treatment with these drugs can modify the progression of CF disease in children.
• Collaborative Efforts: The Cystic Fibrosis Foundation's venture philanthropy model and collaborations with biotech and pharmaceutical companies are crucial for advancing CF treatments.
• Future Prospects: Ongoing research and development are expected to lead to more effective treatments for all people with CF.

FAQs

What is the mechanism of action of ivacaftor and lumacaftor in treating cystic fibrosis?

Ivacaftor acts as a CFTR potentiator, increasing the time the CFTR channel is open, while lumacaftor corrects the defective CFTR protein by improving its maturation, trafficking, and cell surface stability.

How have the Phase 3 trials of ivacaftor and lumacaftor impacted the treatment of cystic fibrosis?

The Phase 3 trials have shown significant improvements in lung function and reduced pulmonary exacerbations for patients with the F508del mutation, marking a major milestone in CF treatment.

What is the projected growth of the cystic fibrosis market?

The market is expected to grow from $2.1 billion in 2015 to approximately $7.6 billion by 2025, representing a compound annual growth rate of 13.6 percent.

How early can children with cystic fibrosis start treatment with ivacaftor and lumacaftor?

Children as young as 2 years old can start treatment with ivacaftor and lumacaftor, which has been shown to modify early disease progression.

What role has the Cystic Fibrosis Foundation played in the development of ivacaftor and lumacaftor?

The Cystic Fibrosis Foundation has provided substantial clinical and financial support, including $75 million in research funding, through its innovative venture philanthropy model.

Sources

1. Cystic Fibrosis Foundation, "Cystic Fibrosis Foundation Applauds Successful Phase 3 Results of Ivacaftor in Combination with Lumacaftor."
2. Drug Discovery Trends, "Report: Cystic Fibrosis Market Will Rocket to $7.6B by 2025."
3. Therapeutic Goods Administration, "Australian Public Assessment Report for lumacaftor ivacaftor."
4. FDA, "206038Orig1s000 - accessdata.fda.gov."
5. PubMed, "Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children."