Vertex Gains CHMP Nod for KAFTRIO® Label Expansion in Rare CF Mutations
Vertex Pharmaceuticals (Nasdaq: VRTX) has announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the expansion of the label for KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor. This expansion would include the treatment of cystic fibrosis (CF) patients aged 2 years and older who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Fosca De Iorio, M.D., Vice President of International Medical Affairs at Vertex, expressed enthusiasm about this milestone, stating, “We are thrilled by the positive CHMP opinion in support of expanding the KAFTRIO indication to include all CF patients 2 years and older who produce CFTR protein. If approved, thousands of additional patients across Europe will be eligible for a CFTR modulator, bringing us closer than ever to our goal of getting treatments that address the underlying cause of the disease to all people living with CF.”
Understanding Cystic Fibrosis (CF) and Its Impact
Cystic fibrosis is a rare, life-shortening genetic disorder affecting over 94,000 individuals across North America, Europe, and Australia. It is a progressive, multi-system disease that primarily impacts the lungs, pancreas, liver, gastrointestinal tract, and other organs. The condition arises due to mutations in the CFTR gene, which either result in a defective CFTR protein or a complete lack of it. This deficiency disrupts the normal flow of salt and water across cell membranes, leading to thick, sticky mucus buildup, particularly in the lungs. This accumulation fosters chronic lung infections, progressive lung damage, and significantly reduces life expectancy.
To develop CF, individuals must inherit two faulty CFTR genes, one from each parent. The F508del mutation is the most common CFTR mutation, found in a significant majority of patients. However, other rare mutations also contribute to CF, creating the need for expanded treatment options.
Currently, Vertex’s CF medications treat over 68,000 people across more than 60 countries spanning six continents. This represents approximately two-thirds of diagnosed CF patients who are eligible for CFTR modulator therapy.
Importance of the CHMP Positive Opinion
The CHMP’s recommendation is a crucial step toward ensuring broader access to KAFTRIO in Europe. In the EU, KAFTRIO in combination with ivacaftor is already approved for patients aged 2 years and older with at least one copy of the F508del mutation. If the European Commission follows CHMP’s recommendation and grants approval, KAFTRIO’s indication will extend to CF patients with non-class I mutations, significantly increasing the number of eligible patients who can benefit from CFTR modulator therapy.
CF Diagnosis and Treatment Advances
Diagnosis of CF often involves genetic testing alongside the sweat chloride (SwCl) test, which measures CFTR protein dysfunction. The threshold for diagnosing CF is SwCl ≥60 mmol/L, while levels between 30-59 mmol/L indicate potential CF, requiring additional testing. SwCl levels below 30 mmol/L are seen in carriers who do not exhibit CF symptoms.
Restoring CFTR function and reducing SwCl levels are key treatment objectives. Lower SwCl levels correlate with improved lung function, fewer pulmonary exacerbations, better quality of life, and increased survival rates. Vertex has long pursued the goal of bringing SwCl levels below 30 mmol/L, as this is the range typical of CF carriers who do not manifest symptoms.
How KAFTRIO® Works
KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor is an oral CFTR modulator designed to enhance CFTR protein function at the cell surface. Different CFTR mutations cause varying degrees of CFTR dysfunction, either by misfolding the protein, preventing its proper transport to the cell surface, or impairing its ability to facilitate chloride ion movement. KAFTRIO targets these defects in the following ways:
- Elexacaftor and tezacaftor: These correctors help increase the number of mature CFTR proteins at the cell surface by binding to different sites on the protein, improving its stability and function.
- Ivacaftor: As a CFTR potentiator, ivacaftor enhances the activity of CFTR proteins Vertex that reach the cell surface, facilitating proper ion transport and reducing mucus buildup.
By improving CFTR protein quantity and functionality, KAFTRIO works to Vertex restore salt and Vertex water balance in epithelial tissues, thereby mitigating CF symptoms and slowing disease Vertex progression.
Broader Implications of Approval
If the European Commission grants approval, thousands more CF patients with rare mutations will gain access to an effective treatment option that targets the underlying cause of their disease. This would be a significant step forward in Vertex’s ongoing mission to make CFTR modulator therapy available to all eligible CF patients.
Additionally, the approval could pave the way for further research and development in CF therapeutics, reinforcing the importance of targeted, mutation-specific treatments. As Vertex continues to push the boundaries of CF treatment innovation, expanding the reach of its therapies aligns with its broader vision of transforming the lives of all people with CF.
Next Steps
The European Commission typically follows CHMP recommendations and is expected to issue its final decision in the coming months. If approved, the label expansion will allow healthcare providers to prescribe KAFTRIO to a wider CF population, improving treatment accessibility across Europe.
Vertex remains committed to advancing CF research and ensuring that as many patients as possible receive life-changing treatment. The company will continue working closely with regulators, healthcare providers, and patient communities to maximize the impact of its therapies.
For more information, the Summary of Product Characteristics can be found on the EMA website at www.ema.europa.eu.
