Cystic Fibrosis Pipeline Insights

Executive Summary

Cystic Fibrosis is caused by mutations in the CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator), located on chromosome 7. The CFTR gene produces a protein that regulates the movement of chloride ions across the cell membranes, which is crucial for maintaining the balance of salt and water in cells, particularly in the lungs and other organs. In individuals with CF, the CFTR protein is defective or absent, leading to thick, sticky mucus production. This mucus accumulates in various parts of the body, such as the lungs, pancreas, intestines, and other organs, causing a range of symptoms and complications.

Clinical trials help test combinations of therapies that might offer enhanced benefits. For instance, Trikafta, a combination of three drugs (Ivacaftor, Tezacaftor and Elexacaftor), was approved after successful trials for a broader range of CF patients and has shown dramatic improvements in lung function and overall health. CF clinical trials increasingly focus on personalized treatment based on specific genetic mutations, as different CF mutations respond differently to treatments. This personalized approach ensures that therapies are tailored to the genetic profile of the individual patient, improving outcomes.

List of Key Companies

The major and key players in the cystic fibrosis pipeline include

• Spirovant Sciences, Inc.

SP-101: SP-101 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a human CFTR minigene, Human CFTR with a deleted regulatory domain, and is being investigated as an inhalation treatment for people with cystic fibrosis.

• Vertex Pharmaceuticals Incorporated

VX-522: VX-522 is an investigational messenger ribonucleic acid (mRNA) therapy that aims to address the underlying cause of cystic fibrosis (CF). It is being evaluated by Vertex to treat lung disease for people living with CF who cannot benefit from cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatments because they do not make any CFTR protein that responds to a CFTR modulator therapy.

• SpliSense Ltd.
• Enterprise Therapeutics Ltd
• Boehringer Ingelheim International GmbH
• 4D Molecular Therapeutics
• Clarametyx Biosciences, Inc.
• Arcturus Therapeutics, Inc.
• Krystal Biotech, Inc.
• Cystetic Medicines, Inc.
• Kither Biotech Srl
• ReCode Therapeutics

Regulatory Designations

• In March 2024, 4D Molecular Therapeutics announced an update on its regulatory interactions and development path for 4D-710, an aerosolized genetic medicine for the treatment of CF lung disease.
• In July 2024, Vertex Pharmaceuticals Incorporated announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for investigational once-daily vanzacaftor/tezacaftor/deutivacaftor triple combination therapy (vanza triple) for people living with cystic fibrosis (CF) ages 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsive to the vanza triple.

Future Perspectives and Conclusion

The Cystic Fibrosis (CF) pipeline market holds immense promise, driven by ongoing advancements in molecular biology, genetic research and drug discovery. As the CF treatment landscape evolves, several key trends are shaping the future of the market, with both biopharmaceutical companies and patients reaping significant benefits.

The CFTR modulator class, which aims to target the root cause of CF by improving the function of the CFTR protein, continues to dominate the pipeline market. Since the approval of Ivacaftor (Kalydeco) in 2012, and its subsequent combinations like Orkambi and Trikafta, these drugs have revolutionized CF treatment. The future of this market will see further enhancement of these modulator therapies, targeting broader patient populations and a wider array of genetic mutations.

For instance, Trikafta, which was approved in 2019, is a triple-combination therapy that has shown remarkable clinical improvements for a larger group of patients with CF, even those without the most common mutations. As more modulators enter clinical trials and potentially gain approval, a comprehensive, personalized treatment approach could become the standard of care, offering broader efficacy across diverse genetic profiles.

Gene therapy is expected to be one of the most transformative developments in CF treatment. Research into gene editing technologies aims to correct the genetic mutations that cause CF. The ability to deliver a functional copy of the CFTR gene to CF patients could lead to long-term or permanent improvements in CF management, offering the possibility of a functional cure.

For instance, several gene therapy trials are already in progress, such as those by Boehringer Ingelheim International GmbH and 4D Molecular Therapeutics, which are exploring gene therapies for CF. While still in early stages, these therapies could dramatically shift the treatment paradigm, reducing dependency on chronic medications.