Cystic Fibrosis Awareness Month – May 2021

News & Events

May 28

Background on Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening, genetic disorder which affects multiple organs, predominantly the lungs and pancreas. CF is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) gene, and both copies of the faulty CFTR gene must be inherited to develop CF. This defective CFTR gene causes the abnormal production of sweat and mucus.

Through sweating, CF patients lose excessive amounts of salt, causing abnormal heart rhythms, risk of shock, stroke, and decreased blood pressure. Mucus accumulating in the intestines and lungs results in malnutrition, poor growth, respiratory infections, breathing difficulties, and eventually permanent lung damage. Subsequently, lung disease is the most common cause of death in most CF patients.

Although classified as an orphan disease, CF is estimated to effect 75,000 people worldwide, with symptoms usually appearing in early childhood and progressing over time. The median age of death is in the early 30s.

While there is no current cure, treatment options to improve lung function, called CFTR modulators, cover 90% of CF patients. However, there remains a need for effective therapies to address infection, inflammation, irreversible lung disease and extrapulmonary complications of CF. In addition, a high unmet need remains in improving mortality and providing treatment options for the 10% of patients where CFTR modulators are not available.

Historical Challenges with Reimbursement of CF Products

Vertex Pharmaceuticals, leaders in CF and the manufacturers of precision medicines Kaftrio, Orkambi, Symkevi and Kalydeco, have faced significant reimbursement challenges. Most notably in the UK, where there was a 4-year delay between EMA authorisation and the time to patient access to Orkambi and Symkevi.

NICE questioned long-term impact on patient mortality; however, the predominant issue was the lack of cost-effectiveness at the proposed price. NHS England also considered their budget impact to be prohibitive, with disproportionate spending relative to other therapy areas. The standoff between NICE, NHS England and Vertex over the price of CF drugs resulted in campaigns from patient groups to make the drugs available. Finally, a managed access agreement was arranged in October 2019 for the 50% of CF patients who Orkambi and Symkevi provided a treatment option for.

Since then, although many NICE technology appraisals were delayed during the COVID-19 pandemic, those designated as “therapeutically critical” were prioritised, including Kaftrio (or Trikafta in the US), a fixed dose combination for treating CF patients with the F508del mutation.

The Future of CF Treatments

Kaftrio, is known as the “triple combination therapy” and well respected for its therapeutic value, providing an option for 90% of CF patients. It received the highest grade for therapeutic evidence by ICER, Institute of Cost Effectiveness Research, in the US, and was authorised by NHS England in June 2020, as soon as EMA gave the green light. NHS patients were among the first in Europe to be prescribed Kaftrio, which significantly improves lung function, enhancing overall quality of life for CF patients. With its “digital” launch, Kaftrio has quickly become one of the most successful drugs in terms of revenue for 2020.

This step in CF offers a lifeline to those with limited treatment options; however, more work remains and further breakthroughs are necessary to support all people with CF. Ongoing data collection is underway to provide real-world evidence for approved CF drugs to investigate if broader patient access will be a future possibility. In addition, there is an active pipeline with assets by Vertex, Abvie and Eloxx Pharmaceuticals in Phase II studies.

Rare diseases represent a challenging field for pharmaceutical development, with their small trial sample size, challenges in diagnosis and limited available data. However, novel therapies in Cystic Fibrosis are overcoming these challenges and looking ahead to a promising future.