CHF 5993, an investigative triple combination treatment, is fixed-dose and fine-particle inhalation therapy consisting of beclomethasone dipropionate (BDP), formoterol fumerate (FF) and glycopyrronium bromide (GB). Also known as a ICS-LABA-LAMA combination, CHF 5993 is the first such extra-fine fixed triple combination being developed for COPD, or chronic obstructive pulmonary disease.

The treatment, now being tested in clinical trials, is a dry powder delivered using a pressurized metered dose inhaler (pMDI). This consists of a handheld device with an attached mouthpiece that allows for the active ingredient to go directly to the lungs.

Active ingredients and intended effects of CHF 5993

The drug’s three active ingredients work on different levels:

  • Beclomethasone is an inhaled corticosteroid (ICS) that has anti-inflammatory properties.
  • Formoterol and glycopyrronium are both long-acting bronchodilators, which work to open the airways to facilitating breathing. Formoterol is a beta2-agonist (LABA), which relaxes the muscles of the airways, and glycopyrronium is a long-acting muscarinic antagonist (LAMA), which blocks bronchial constriction of airway smooth muscles.

The triple combination is designed to improve airflow, and to reduce the risks of COPD exacerbations (sudden flares of existing symptoms or of new ones).

CHF 5993 is being developed by Chiesi Farmaceutici for the treatment of COPD (chronic obstructive pulmonary disease) and asthma.

CHF 5993 and clinical trials

A Phase 1 study (NCT02040597) evaluated the pharmacokinetics, safety, and tolerability of CHF 5993 in healthy volunteers and people with with mild, moderate and severe renal impairment (but not COPD or asthma). Participants were given four inhalations of a single dose of the combination — BDP (100 mcg), FF (6 mcg), and GB (25 mcg). Results among renal patients were compared with matched healthy participants, and showed that CHF 5993 had good and similar safety profiles in both groups.

Two Phase 3 studies of CHF 5993 as a COPD treatment were completed in 2016. One study, NCT01911364, evaluated the efficacy and safety of CHF 5993 compared to a comparator drug, tiotropium, either alone or in a fixed combination of beclomethasone and formoterol fumarate (marketed by Chiesi as Foster) plus tiotropium. Its primary measures were the treatment’s effect on COPD exacerbations rates and, as a secondary goal, on lung health as measured by FEV1. Results showed that the treatments were safe and well-tolerated and that the efficacy of CHF 5993 was superior to that of tiotropium in reducing exacerbations. Non-inferiority was also demonstrated. The other study, NCT01917331, compared the CHF 5993 triple combination to that of Foster in a twice daily dose given nearly 1,370 people with severe to very severe COPD. One-year results, published in The Lancet in September 2016, showed CHF 5993 was superior in reducing exacerbations and in promoting pulmonary function, demonstrating its clinical benefits as a triple-therapy single inhaler.

A third Phase 3 study (NCT02467452), aimed at demonstrating the equivalent effectiveness of CHF 5993 (BDP at 100 mcg, FF at 6 mcg, and GB at 25 mcg) to that of two comparative treatments reportedly finished in January 2017. Results of this study, in about 1,500 COPD patients, are not yet available.

Another Phase 3 study is ongoing (NCT02579850, known as TRIBUTE), evaluating the effectiveness of the CHF 5993 triple combination to that of the Ultibro Breezhaler (marketed by Novartis). About 1,500 people with severe or very severe COPD are enrolled in this 52-week study, which is expected to finish in July 2017.

Other details

A Phase 1 study (NCT02743013) evaluated the pharmacology of CHF 5993 in 50 healthy participants, randomized to receive the drug via different administration modes: a dry powder inhaler (DPI) and a pressured metered dose inhaler (pMDI) with and without a valved holding chamber. The study ended in July 2016.

The triple combination of beclomethasone dipropionate, formoterol fumerate, and glycopyrronium bromide is also being tested in clinical trials as a possible treatment for asthma (NCT02676076NCT02676089NCT02975843 and NCT02359292).

 

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