Cystic fibrosis - Emerging treatments

The Cystic Fibrosis Foundation website includes an interactive drug development pipeline that lists interventions that are in preclinical development, in clinical trials, or have been approved for use. Cystic Fibrosis Foundation: drug development pipeline Opens in new window Emerging therapies encompass treatments for symptoms of CF as well as newer therapies aimed at treating the underlying basic defect in CF patients.[130]

Multicomponent strategies and digital technology

Multicomponent self-management interventions (e.g., logging nebulizer use, using digital platforms, and detailing behavioral interventions) may increase treatment adherence, reduce the perceived burden of disease, and increase BMI, but do not appear to affect respiratory exacerbations.[131] One Cochrane review reported that digital monitoring plus tailored support via an online platform may improve treatment adherence and reduce the burden of treatment in the medium term.[132] [ ] [Evidence B] A second could only report moderate‐certainty evidence that psychological interventions improve adherence to inhaled therapies.[133] A third Cochrane review found that recording spirometry and symptoms probably allowed the earlier identification of exacerbations, but without significant effects on the number of exacerbations warranting intravenous antibiotics, on lung function, or on quality of life (QoL) scores.[134] [ ] Finally, a fourth reported very uncertain evidence about the benefits of wearable fitness trackers alone or in combination with a social media platforms or personalized exercise prescriptions.[135]

Inhaled colistimethate sodium (dry powder)

Colistimethate sodium dry powder for inhalation was non-inferior to tobramycin inhalation solution with respect to lung function after 24 weeks of treatment in one open-label study of patients with CF (ages 6 years and older) with chronic Pseudomonas aeruginosa lung infection.[136] Colistimethate sodium powder for inhalation is approved for this indication in Europe, but not in the US.

Cysteamine

Cysteamine (also known as NM001), a unique molecule with a dual antibacterial-mucoactive mode of action, has been granted orphan drug designation by the Food and Drug Administration (FDA). It is being developed as an oral form for acute exacerbations and in an inhaled dry powder form for chronic use and maintenance. Cysteamine is intended for application alongside existing CF treatments to potentiate antimicrobial effects. One phase 2 randomized clinical trial concluded that oral cysteamine was safe and well tolerated in adult patients experiencing a pulmonary exacerbation of CF.[137]

Inhaled gallium citrate (AR-501)

AR-501 is an inhaled formulation of gallium citrate with broad-spectrum nonantibiotic, anti-infective activity. It is being developed as a self-administered, weekly treatment for lung infection in patients with CF. It is a small molecule, in which gallium functions as an iron analog that antagonizes multiple iron-dependent pathways in microbes, thereby counteracting multiple key functions in bacteria. Preclinical efficacy and safety data have demonstrated that AR-501 works synergistically with multiple antibiotics, is effective against antibiotic-resistant strains, and has a low intrinsic resistance profile. It is being evaluated in an ongoing phase 1/2a clinical trial.[138] It has been granted orphan drug designation by the FDA for the treatment of lung infection in patients with CF.

MRT5005

MRT5005, the first mRNA therapeutic with delivery to the lung, is designed to address the underlying cause of CF by delivering mRNA encoding fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to cells in the lung through nebulization. MRT5005 is being developed to treat all patients with CF, regardless of the underlying genetic mutation, including those with limited or no CFTR protein. A phase 1/2 clinical trial of MRT5005 is currently ongoing. The FDA has granted orphan drug and fast-track designation for MRT5005 for the treatment of CF.[139]

Glutathione

One Cochrane review reported that inhaled and oral glutathione appear to improve lung function, while oral administration decreases oxidative stress.[140] Further studies are needed to confirm this effect, which may be confounded by use of any concurrent treatments, including an intensive course of antibiotics.

Mannitol

Inhaled mannitol, an osmotic agent administered as a dry powder, can improve lung function in people with CF compared with controls.[141] In one double-blind randomized clinical trial, mannitol led to significantly improved FEV₁ over 26 weeks in adult CF patients compared with a control group. Adverse effects were mainly mild or moderate.[142] A randomized clinical trial in children has also shown significant improvements in lung function among patients with CF ages over 6 years.[143]

Ataluren

One phase 3 clinical trial found no significant difference in absolute change in average ppFEV₁ between ataluren (an orally administered drug that targets nonsense mutations) and placebo in subjects ages ≥6 years with nonsense-mutation CF.[144] One Cochrane review also found that results were not clinically significant.[145] [ ] [Evidence A]

Appetite stimulants

Appetite stimulants may improve weight (or z score) and subjectively reported appetite.[146] However, the lack of data on associated adverse effects limits their clinical utility.