Question 1

What is cystic fibrosis?

Accepted Answer

Cystic fibrosis is the most common serious genetic disease in populations of Northern European descent — caused by mutations in the CFTR gene that impair or eliminate function of the CFTR chloride channel. This results in dehydrated, thick and sticky mucus in the airways, pancreas, gastrointestinal tract and reproductive organs. The thick airway mucus promotes chronic bacterial infection, progressive bronchiectasis and declining lung function — the primary cause of death. CF affects approximately 100,000 people globally.

Question 2

What are CFTR modulators?

Accepted Answer

CFTR modulators are small molecule drugs that target the underlying CFTR protein defect — rather than managing symptoms. They fall into two classes: correctors (restore CFTR protein trafficking to the cell surface — elexacaftor, tezacaftor); and potentiators (increase the time the CFTR channel gate stays open — ivacaftor). The triple combination Trikafta (elexacaftor/tezacaftor/ivacaftor) is highly effective for patients with at least one F508del allele (approximately 90% of CF patients), dramatically improving lung function, nutritional status, exacerbation rates and quality of life.

Question 3

How did Trikafta transform CF?

Accepted Answer

Before CFTR modulators, CF management was entirely symptomatic — airway clearance, antibiotics, enzyme replacement — and median survival was approximately 30-35 years. Trikafta (approved 2019) achieved unprecedented benefits: approximately 10-14% improvement in ppFEV1; 40-60 mmol/L reduction in sweat chloride; 63-65% reduction in pulmonary exacerbations; substantial BMI improvement; significant quality of life improvement. Projected median survival has increased to over 55 years for those accessing the drug. It is described as transformative — "a cure in a pill" for many (though it does not eliminate the underlying mutations).

Question 4

Who is eligible for Trikafta?

Accepted Answer

Trikafta is approved for patients aged ≥2 years (US) or ≥2 years (EU) with: one or two copies of the F508del CFTR mutation; or one copy of F508del plus certain other mutations (a list of "minimum function" mutations). This covers approximately 90% of CF patients globally. The approximately 10% of patients with rare mutations causing minimal or absent CFTR expression (Class I mutations — premature stop codons) cannot yet benefit from current modulators — though gene therapy approaches are in development for them.

Question 5

What is the access crisis for Trikafta?

Accepted Answer

Trikafta costs approximately $300,000/year per patient in the US — one of the most expensive medications per patient per year. In high-income countries with robust healthcare systems, most CF patients access it through reimbursement negotiations with Vertex Pharmaceuticals (which developed and holds patents on all approved CFTR modulators). In LMICs and many middle-income countries, Trikafta is completely inaccessible — leaving tens of thousands of CF patients without potentially life-transforming treatment. This is one of the most prominent examples of the global medicine access gap.

Question 6

How is CF managed beyond CFTR modulators?

Accepted Answer

Even with Trikafta, symptomatic management remains important: airway clearance therapy (chest physiotherapy, oscillating PEP devices, hypertonic saline nebulisation — 2-4x daily); inhaled antibiotics (tobramycin, aztreonam for Pseudomonas); oral azithromycin (anti-inflammatory); dornase alfa (DNase — reduces viscosity of airway secretions); pancreatic enzyme replacement (for exocrine pancreatic insufficiency — 85% of CF patients); nutritional support; CF-related diabetes management (common in adults); and lung transplantation for end-stage disease.

Question 7

How is CF inherited?

Accepted Answer

CF follows autosomal recessive inheritance — requiring two defective CFTR alleles (one from each parent). Carriers (one normal + one mutated CFTR allele) are completely healthy. In populations of Northern European ancestry, approximately 1 in 25 people is a carrier. Risk for a CF child when both parents are carriers: 25% (CF), 50% (carrier), 25% (non-carrier). Prenatal diagnosis, preimplantation genetic testing and cascade carrier testing (offering testing to relatives of diagnosed CF patients) are standard in high-income countries.

Question 8

What does the future hold for CF?

Accepted Answer

The CF research agenda: extending CFTR modulator access to LMIC populations (through generic production, tiered pricing or compulsory licensing); developing therapies for the approximately 10% of patients with Class I mutations (premature stop codons) — read-through agents (ataluren — limited efficacy), gene therapy (AAV vectors, mRNA therapy — early clinical trials), and gene editing; preventing Pseudomonas chronic infection; and managing CF complications (CF-related diabetes, liver disease, CF-related bone disease).

Question 9

How does GMJ News cover cystic fibrosis?

Accepted Answer

GMJ News covers CF Foundation data, Trikafta approval and global access inequity, CFTR modulator mechanism, gene therapy pipeline and CF care standards. CF is part of the GMJ's rare genetic disease and orphan drug access coverage — directly relevant to PHIG's rare disease agenda and the Georgian Medical Journal.

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