Modulators and Gene Therapy Transforming Cystic Fibrosis (CF) Therapeutics

Highlights: 

• A look into cutting-edge modulators used in CF treatment 

• Key innovations in offering potential cure alternatives for CF 

• Profitable partnership by industry leaders in the sector 

Cystic fibrosis (CF) is a life-shortening genetic disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which leads to thick, sticky mucus build-up in various organs. Previously, CF management mostly focused on symptom relief by providing antibiotics for infections, mucus thinners, and physiotherapy. Over the last few years, the landscape has been transformed by the development of drugs that target the underlying molecular defect and rapid advancements in gene therapy and precision medicine. 

Evolving modulator therapies for cystic fibrosis 

The most significant breakthrough in CF treatment is the advent of CFTR modulators, which restore or enhance the function of defective CFTR protein. These drugs are tailored to specific mutations and have dramatically improved outcomes for many patients. For instance, Trikafta, a CFTR modulator, marketed as Kaftrio in Europe, has offered positive outcomes in CF therapeutics. It is a triple combination therapy for patients aged 12 and older with at least one F508del mutation, the most common CF mutation, present in about 90% of cases. 

Trikafta combines two correctors, elexacaftor and tezacaftor that help the CFTR protein fold and reach the cell surface, and a potentiator that keeps the channel of the protein open for chloride transport. This therapy has led to significant improvements in lung function, quality of life, and life expectancy and offered patients utmost relief from symptoms such as chronic coughing. The other two CFTR modulators include kalydeco and orkambi. Kalydeco is the first modulator that is effective for certain gating mutations. On the other hand, orkambi is an earlier combination therapy for patients with specific mutations.  

Next-gen cystic fibrosis treatments redefining CF care 

The cystic fibrosis therapeutics industry has witnessed prominent growth due to the rapid development of advanced treatments for the disease. ENaC blockers, such as ETD001 developed by Enterprise Therapeutics, represent a promising new approach for cystic fibrosis (CF) patients who cannot benefit from CFTR modulators. ETD001 targets the epithelial sodium channel (ENaC), which is not mutated in CF, to increase airway hydration and enhance mucus clearance. This mechanism is mutation-agnostic, making it suitable for all CF patients, including the 10% who are ineligible for CFTR modulators. As per early clinical studies, ETD001 works for a long time and appears safe. Phase 2 trials are now testing how well it improves lung function. It aims to reduce lung infections and improve quality of life for underserved CF patients, by hydrating mucus and improving its clearance. 

Furthermore, gene therapy and gene editing have emerged as groundbreaking strategies for cystic fibrosis (CF), aiming to address the disease at its genetic source. Current research focuses on inhalable gene therapies that deliver functional CFTR genes directly to airway cells. Simultaneously, emphasis on advanced gene-editing techniques like CRISPR/Cas9 and prime editing help precisely correct or replace faulty CFTR DNA. These approaches give hope for all CF patients, including those with mutations unresponsive to current drugs. Such treatments show potential for restoring CFTR function, such as ensuring efficient delivery to lung tissue, achieving durable effects, and avoiding immune reactions.  

Sionna Therapeutics expanded CF pipeline with AbbVie licensing deal 

In July 2024, Sionna Therapeutics strengthened its cystic fibrosis pipeline through a strategic licensing deal with AbbVie, an America pharmaceutical company. The agreement granted Sionna rights to develop and commercialize three clinical-stage CF compounds, including two in Phase II and one in Phase I. This initiative boosted AbbVie’s limited success in CF drug development and highlighted Sionna’s innovative potential. In addition, the partnership enhanced Sionna’s therapeutic capabilities, helping it grow as a key player in the CF treatment landscape with expanded options for unmet patient needs. 

Wrapping up 

With the rise of advanced CFTR modulators, cystic fibrosis treatment is rapidly evolving from symptom management to targeted and disease-modifying approaches. These innovations offer renewed hope for all CF patients, transforming CF from a fatal disease to a manageable chronic condition. 

To get more information about the upcoming advancements in cystic fibrosis therapeutics, reach out to our industry specialists today! 

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