CLINICAL TRIALS PROFILE FOR ORKAMBI

All Clinical Trials for Orkambi

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02170025 ↗	Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients	Terminated	Merck Sharp & Dohme Corp.	Phase 2	2014-09-30	Assessment of the safety, tolerability and early signs of efficacy of three times a day orally administered BAY63-2521 in adult delta F508 homozygous Cystic Fibrosis patients not on treatment with Orkambi
NCT02170025 ↗	Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients	Terminated	Bayer	Phase 2	2014-09-30	Assessment of the safety, tolerability and early signs of efficacy of three times a day orally administered BAY63-2521 in adult delta F508 homozygous Cystic Fibrosis patients not on treatment with Orkambi
NCT02589236 ↗	Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation	Completed	Medidata Solutions	Phase 2	2015-11-01	This will be a double-blind, randomized, placebo-controlled, parallel group study. The purpose of this study is to investigate the efficacy and safety of Cavosonstat (N91115) in adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with lumacaftor/ivacaftor (Orkambi™).
NCT02589236 ↗	Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation	Completed	Nivalis Therapeutics, Inc.	Phase 2	2015-11-01	This will be a double-blind, randomized, placebo-controlled, parallel group study. The purpose of this study is to investigate the efficacy and safety of Cavosonstat (N91115) in adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with lumacaftor/ivacaftor (Orkambi™).
NCT02653027 ↗	Effect of Lumacaftor-ivacaftor on Glucose Handling and Tolerance in Cystic Fibrosis Phe508del	Withdrawn	Massachusetts General Hospital	N/A	2018-01-01	The purpose of this research study is to find out if the combined therapy lumacaftor-ivacaftor effects how people with cystic fibrosis respond to an oral glucose tolerance test, a test for diabetes.
NCT02709109 ↗	A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2016-02-01	The purpose of this study is to evaluate the safety and efficacy of treatment with VX-371 in hypertonic saline compared to hypertonic saline alone in subjects with cystic fibrosis (CF) who are ≥12 years of age, homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation, and being treated with Orkambi
NCT02709109 ↗	A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation	Completed	Parion Sciences	Phase 2	2016-02-01	The purpose of this study is to evaluate the safety and efficacy of treatment with VX-371 in hypertonic saline compared to hypertonic saline alone in subjects with cystic fibrosis (CF) who are ≥12 years of age, homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation, and being treated with Orkambi

Clinical Trial Conditions for Orkambi

Condition Name

Condition Name for Orkambi
Intervention	Trials
Cystic Fibrosis	17
Diabetes	2
Healthy Volunteer	1
Homozygous F508del Mutation	1

Condition MeSH

Condition MeSH for Orkambi
Intervention	Trials
Cystic Fibrosis	17
Fibrosis	16
Hyperglycemia	1
Lung Diseases	1

Clinical Trial Locations for Orkambi

Trials by Country

Trials by Country for Orkambi
Location	Trials
United States	123
Germany	9
Canada	8
France	5
United Kingdom	3

Trials by US State

Trials by US State for Orkambi
Location	Trials
Ohio	6
Massachusetts	6
Illinois	6
North Carolina	6
Kansas	5

Clinical Trial Progress for Orkambi

Clinical Trial Phase

Clinical Trial Phase for Orkambi
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	2
Phase 2	6

Clinical Trial Status

Clinical Trial Status for Orkambi
Clinical Trial Phase	Trials
Completed	8
Recruiting	6
Terminated	3

Clinical Trial Sponsors for Orkambi

Sponsor Name

Sponsor Name for Orkambi
Sponsor	Trials
Vertex Pharmaceuticals Incorporated	4
National Heart, Lung, and Blood Institute (NHLBI)	2
Children's Hospital Medical Center, Cincinnati	2

Sponsor Type

Sponsor Type for Orkambi
Sponsor	Trials
Other	15
Industry	12
NIH	2

Clinical Trials, Market Analysis, and Projections for Orkambi

Introduction

Orkambi, a combination therapy of lumacaftor and ivacaftor, has been a significant player in the treatment of cystic fibrosis (CF), particularly for patients with the F508del mutation. Here, we will delve into the clinical trials, market analysis, and projections for this drug.

Clinical Trials Overview

Trials 1 and 2: Phase 3 Studies for Patients 12 Years and Older

Trials 1 and 2 were 24-week, Phase 3, randomized, double-blind, placebo-controlled studies involving patients aged 12 years and older who were homozygous for the F508del-CFTR mutation. These studies evaluated the efficacy and safety of Orkambi, with primary endpoints including the absolute change in percent predicted FEV₁ (ppFEV₁) from baseline at Week 24. The results showed statistically significant improvements in lung function and other clinical outcomes, such as a reduction in pulmonary exacerbations and an improvement in the CFQ-R Respiratory Domain score[4].

Trial 3: Open-Label Safety Study for Patients 6-11 Years

Trial 3 was a 24-week, open-label study assessing the safety, tolerability, and pharmacokinetics of Orkambi in patients aged 6 through 11 years with CF who were homozygous for the F508del mutation. The study found that Orkambi was generally well-tolerated, with common adverse events including cough, infective pulmonary exacerbation, and nasal congestion. There were also notable increases in liver enzymes, but no patients had significant increases in total bilirubin levels[1].

Trial 4: Double-Blind, Placebo-Controlled Efficacy and Safety Study for Patients 6-11 Years

Trial 4 was a 24-week, double-blind, placebo-controlled study evaluating the efficacy and safety of Orkambi in patients aged 6 through 11 years. The primary endpoint was the absolute change in the Lung Clearance Index (LCI) 2.5 from baseline through Week 24. The results showed a statistically significant improvement in lung function, with a treatment difference vs placebo of -1.1 (95% CI -1.4 to -0.8; P<0.0001)[1].

Market Analysis

Current Market Position

Orkambi, approved by the FDA in 2015, is indicated for the treatment of CF in patients aged 2 years and older who are homozygous for the F508del mutation. Despite its initial success, Orkambi's market share has been declining due to the introduction of more effective treatments like TRIKAFTA and SYMDEKO. In 2021, Orkambi accounted for only 10% of Vertex Pharmaceuticals' product revenues, down from previous years[2].

Competition and Market Dynamics

The CF treatment market is highly competitive, with Vertex Pharmaceuticals being the global leader. TRIKAFTA, a combination of three drugs, has significantly outperformed Orkambi in terms of efficacy and market share. TRIKAFTA generated 75% of Vertex's product revenues in 2021 and is projected to continue growing, further eroding Orkambi's market position[2].

Regulatory Expansions and Challenges

Orkambi has seen regulatory expansions, including a label expansion to treat children aged 6 through 11 years, which added about 2,500 patients to the therapy's eligible treatment pool. However, the drug faces reimbursement challenges, particularly in Germany, which has impacted its sales growth. Despite these challenges, Vertex expects that a favorable pricing decision in Germany could positively influence other major European markets[5].

Projections and Future Outlook

Revenue Projections

Given the consistent negative growth trend, Orkambi is projected to experience a decline in sales. For 2022 and 2023, a -35% and -25% growth, respectively, is anticipated, followed by a steady -15% growth from 2024 onwards. This decline is largely due to the superior efficacy of TRIKAFTA and the ongoing phase 3 studies for new combination drugs[2].

Market Share and Patient Uptake

The market share of Orkambi is expected to diminish as TRIKAFTA continues to dominate the CF treatment market. However, higher compliance rates among younger patients, attributed to parental involvement, may offer some stability in patient uptake for Orkambi, although this is not expected to offset the overall decline[5].

Future Clinical Studies

There are ongoing efforts to generate further clinical data, including post-authorization studies and phase 3 trials for new combination drugs. These studies may provide additional insights into the long-term efficacy and safety of Orkambi, but they are unlikely to reverse the current market trends[3].

Key Takeaways

• Clinical Trials: Orkambi has demonstrated safety and efficacy in various clinical trials across different age groups, but its benefits are overshadowed by newer treatments.
• Market Analysis: Orkambi's market share is declining due to competition from more effective treatments like TRIKAFTA.
• Projections: Orkambi is projected to experience significant revenue decline in the coming years.
• Regulatory and Compliance: Reimbursement challenges and regulatory expansions continue to impact Orkambi's market performance.

FAQs

What is Orkambi used for?

Orkambi is used for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who are homozygous for the F508del mutation in the CFTR gene.

How effective is Orkambi compared to other CF treatments?

Orkambi has shown significant improvements in lung function and other clinical outcomes, but it is less effective compared to newer treatments like TRIKAFTA, which combines three drugs.

What are the common side effects of Orkambi?

Common side effects include cough, infective pulmonary exacerbation, nasal congestion, headache, and increases in liver enzymes.

Why is Orkambi's market share declining?

Orkambi's market share is declining due to the introduction of more effective treatments like TRIKAFTA and ongoing reimbursement challenges.

What are the future prospects for Orkambi?

Orkambi is projected to experience a significant decline in sales and market share, with ongoing clinical studies unlikely to reverse this trend.

Sources

1. Clinical Trials for Ages 6 Years to - ORKAMBI® (lumacaftor/ivacaftor): ORKAMBIHCP.
2. Vertex Pharmaceuticals (NASDAQ: VRTX): University of Iowa Tippie College of Business.
3. Orkambi, INN-lumacaftor & ivacaftor - European Medicines Agency: European Medicines Agency.
4. Clinical Trials for Age 12 Years and Older: ORKAMBIHCP.
5. Vertex scores new Orkambi market but chops sales guidance anyway: FiercePharma.

Last updated: 2025-01-01