- Global Pharma News & Resources

Cystic fibrosis: hope remains for a ‘miracle cure’

Cystic fibrosis: hope remains for a ‘miracle cure’


After the first failure of gene therapy, it's widely accepted that treatment leading to a cure for the 50,000 cystic fibrosis sufferers worldwide is an unachievable goal. The limited R&D efforts are instead directed towards disease modification and symptomatic treatments with ion channel modulators thought to hold some promise for the future.
Last Updated: 27-Aug-2010

Cystic fibrosis is an inherited disease that is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance regulator (CFTR) gene. Although the most common mutation occurs at position 508 in the CFTR gene, advances in genomics have led to the discovery of a further 1,200 mutations. The CFTR mutation causes the chloride channel - which secretes chloride and water - to be blocked, which results in the production of thick mucus. The different mutations result in a wide variation in symptoms and severity of the disease among patients.

However, the consequences of the disease on the lungs are the most important factor, since most morbidity and nearly all mortality in patients with CF are associated with pulmonary disease. Currently, around 1 in 2,500 − 3,500 newborns in Westerns countries are affected by CF and it is estimated that 50,000 individuals worldwide and 7,500 in the suffer from this disease.

CF treatment is not curative

At present, the treatment of cystic fibrosis is not curative and continues throughout a patient’s life, where extended antibacterial use can bring about antibiotic resistance. A first objective in the treatment of cystic fibrosis is targeting the thick mucus in the lungs, which can be achieved with mucolytics.

Datamonitor research has suggested that in moderate and severe CF patients, DNase (such as Roche/Genentech’s Pulmozyme) is favored over other mucolytics because of its impressive data, with hypertonic saline as a second best option.

A second goal in CF treatment is identifying, eradicating, and controlling bacterial infections from the airways. The traditional method of treating pulmonary infections was with intravenous antibiotics, often needing hospitalization to administer. However, the introduction of antibiotics in oral and aerosol forms - such as Chiron’s TOBI (tobramycin) and Schering-Plough/Bayer’s Cipro - has reduced hospital stays, with these drugs now often used as first-line treatment. Unfortunately, physicians treating patients with CF are increasingly faced with several multi-drug-resistant bacterial pathogens, which represent a major challenge.

The final treatment objective in CF is the prevention and treatment of inflammation in the airways. The most commonly used treatments are a combination inhaled corticosteroids and beta2-agonists, such as AstraZeneca’s Symbicort (budesonide/formoterol) and GlaxoSmithKline’s Advair (fluticasone/salmeterol).

R&D activity

Unmet needs in the treatment of cystic fibrosis include an alternative method of administration of currently available drugs, new antibiotics to treat multi-resistant bacterial pathogens, and ultimately a cure.

Most antibiotics in the pipeline focus on the improvement of administration method with Chiron’s TIP a good example. It is a new version of TOBI and is used with a capsule-based inhaler, instead of a nebulizer. TIP is expected to take over a large market share from TOBI if Chiron is able to launch this drug before TOBI’s patent expires. However, the discovery of a completely new class of antibiotics is thought to be some way off.

Hope for ‘miracle cure’ remains

There is hope for two potential cystic fibrosis cures: gene therapy and ion transport restoration. Most mucolytics in the pipeline try to differentiate from currently available mucolytics by providing a new mechanism of action, targeting the actual mucus problem at the base with ion channel therapy instead of just treating symptoms. Inspire Pharmaceuticals' INS-37217 (denufosol tetrasodium), which is presently in Phase III trials, is one such example.

Gene therapy also represents a possible cure for cystic fibrosis; however, the promised ‘miracle cure’ has been slow to materialize and early clinical trials have shown no convincing benefit to date. Targeted Genetics Corporation in collaboration with the Cystic Fibrosis Trust tried to develop CF gene therapy tgAAVCF for 15 years. However, in March 2005 it became apparent that the product failed to meet the primary endpoint in a Phase II clinical trial.

Datamonitor has identified two gene therapies in development for CF; PTC Therapeutic’s PTC-124, (currently in Phase II trials) and Copernicus Therapeutics’ non-viral nanoparticle formulation, which is in Phase I.

Gene therapy may eventually provide a long-term treatment for CF, however, it is difficult to predict how other gene therapies will perform after tgAAVCF’s late stage failure. Therefore, gene therapy as a cure for CF is far in the future and hopes are focused on ion channel therapy to become the next big step in the treatment of CF.

Related research:

§          Stakeholder Opinions: Cystic Fibrosis - Big unmet needs, small steps

§          Chiron: PharmaVitae Profile 2005

§          Genentech: PharmaVitae Profile 2005