US Patients with Cystic Fibrosis Infections Lack Good Options
Cystic fibrosis (CF) is a genetic disease leading to progressive lung inflammation & damage. Impaired host defense results in chronic lower airway bacterial infection, most commonly by Pseudomonas aeruginosa (PA) and Staphylococcus aureus. PA is linked to greater airway inflammation and is a major etiologic factor in disease progression and overall decline in health. Chronic PA infection results in a vicious cycle of infection and inflammation, which causes airway surface damage, airway plugging, which progressively leads to lung function decline and reduced survival. Strategies to administer anti-pseudomonal antibiotics to the airways have been a cornerstone of CF clinical care for many years. PA remains most prevalent bacterial pathogen in CF in adults, and that most closely linked to worse patient outcomes: chronic PA infection is the leading cause of exacerbations, lung function decline and mortality in CF.
Infections will remain a major problem in CF post-CFTR modulator era as patients live longer. In 2020, 57% of CF patients were over 18 years old, compared to only 32% in 1990. The US CF Foundation estimates that by age 25, >30% of patients have moderate to severe lung disease, increasing to >50% by age 35. Most of these patients are colonized with PA and require regular courses of therapy to manage these infections. That continuing need combined with poor tolerance of long-term tobramycin (otoxicity leading to hearing loss, diminished efficacy) and the fact that CFTR modulators only appear to help clear infections in earlier-stage patients leaves a clear unmet need that ColiFin can fill.
ColiFin fills a critical unmet need in treating CF lung infections for the numerous patients who after long-term tobramycin usage see reduced efficacy & tolerance.
Spexis (through its subsidiary EnBiotix) has in-licensed ColiFin®(inhaled colistimethate sodium) from PARI Pharma GmbH, a global leader in nebulized therapies, for worldwide rights ex-Europe. ColiFin® comes from a class of cyclic polypeptide antibiotics (polymyxins), with multi-modal activity against gram-negative pathogens that has so far prevented widespread emergence of resistance. Chronic PA infection requires lifelong antibiotic therapy, so the emergence of multi-drug resistant PA strains is a significant health concern.
Colistimethate sodium (CMS), the active substance in ColiFin®, is a nonactive prodrug of colistin to reduce the toxic side effects of active colistin. ColiFin has been approved in Europe since 2010 at doses of 1 MIU (~80 mg CMS) and 2MIU (~160 mg CMS) administered two or three times daily with the PARI eRapid nebulizer system, and has become a front-line therapy for chronic lung infections in CF with a proven safety & efficacy track record.
We have received from the FDA a “Study may Proceed” letter to initiate a Phase 3 program for ColiFin® in adult and adolescent subjects with cystic fibrosis and chronic PA lung infection to support a future US marketing authorization. The clinical development of ColiFin® is supported by an FDA Orphan Drug Designation for treatment of respiratory infection in patients with cystic fibrosis, Qualified Infectious Disease Product (QIDP) Designation for ColiFin® for the treatment of PA lung infections in CF patients, and Fast Track Designation.