Invasive Candidiasis

Ibrexafungerp for Invasive Candidiasis

Ibrexafungerp for Invasive Candidiasis

Ibrexafungerp (formerly SCY-078), if approved, may be an important therapy for patients battling very serious fungal infections. Ibrexafungerp's unique combination of attributes potentially enable it to address significant unmet medical needs in invasive candidiasis:

  • Broad in vitro and in vivo anti-Candida activity
  • Active against azole- and most echinocandin-resistant Candida strains, including multidrug resistant strains, such as C. auris
  • Developing in both oral and IV formulations, allowing first-line treatment and oral step-down with the same agent
  • Fungicidal activity vs. Candida
  • High tissue penetration, leading high concentrations in the organs commonly affected by fungal infections

Patients with invasive candidiasis currently have limited therapeutic options and face unsatisfactory clinical outcomes, with mortality up to 30% and an increasing rates of resistance to existing therapies.

What is Invasive Candidiasis?

Invasive candidiasis is a serious fungal infection caused by various Candida species that occurs most frequently in immunocompromised patients. The current treatment algorithm for invasive candidiasis includes:

  • Empiric treatment in the hospital for suspected cases
  • Confirmed treatment in the hospital, typically for ICU, surgical patients, and immunocompromised patients, and patients using a central venous
  • Initial IV therapy for about five days (depending on the risk factors of the patient) with oral step-down for about two weeks

Market Need

Despite existing antifungal agents, mortality in this high-risk patient population remains high (up to 30%). Additionally, the increasing emergence of drug-resistant Candida strains has created an urgent need for new treatments:

  • The CDC has listed fluconazole-resistant Candida as a serious threat requiring prompt and sustained action and has also identified a rise in echinocandin resistance, especially among Candida glabrata.
  • The CDC has issued an extraordinary alert for healthcare facilities and providers to be on the lookout for patients with C. auris, a multidrug-resistant strain with high mortality (approximately 60%).

Current treatment guidelines for invasive candidiasis recommend the use of IV echinocandins as first-line therapy for empiric and confirmed cases. If approved for the treatment of invasive candidiasis, Ibrexafungerp (formerly SCY-078) may provide an alternative to current IV echinocandin use and may fulfill the significant current unmet needs in the oral maintenance setting.

If Ibrexafungerp (formerly SCY-078) is approved for the treatment of invasive Candida infections, we believe it could complement or replace IV echinocandins as the drug of choice for these infections due to its broad spectrum of activity and its availability in both IV and oral forms. The flexibility of access to both formulations would allow physicians and their patients to start and stay on a single effective therapy for both inpatient and outpatient settings. Transitioning patients from hospital-based care to outpatient care is key to potentially reduce, or eliminate, expensive hospital stays and risks of hospital-acquired infections.

“Invasive fungal infections will not go away any time soon. Therefore, we need to circumvent resistance to treatment by continued discovery and development of new antifungal agents and strategies.”

- Dr. John R. Perfect
Nature Reviews/Drug Discovery

Patients with invasive candidiasis face daunting odds for treatment and recovery:

  • Up to 30% mortality rate
  • Limited (only three classes of antifungals) options
  • Multidrug resistance is on the rise
  • The only available oral option today is the azole class, for which resistance is increasing, illustrating the need for novel agents

Resistant Candida: A Serious Public Health Threat

The CDC has listed fluconazole-resistant Candida as a serious public health threat, requiring prompt and sustained action.

  • Approximately 7% of all Candida bloodstream infections are resistant to fluconazole, the majority of which are C. glabrata infections
  • Recent published research reports an increase in C. glabrata infections of ~16%.
  • Echinocandin resistance is also on the rise and accounts for 1-3% of all candida infections and 5-7% of all C. glabrata infections
  • Resistance rates are significantly higher in special populations including immunocompromised and cancer patients and/or those patients in specific healthcare centers
  • Recent worldwide appearance of multidrug resistant Candida auris

Clinical Trial Results

Clinical experience to date has provided promising evidence of clinical antifungal activity of oral ibrexafungerp (formerly SCY-078) in patients with Candida infections.

(ClinicalTrials.gov Identifier: NCT02244606)

PK/Efficacy
  • Ibrexafungerp oral dose of 750mg QD identified, achieving target exposure in patients
  • 27 patients with invasive candidiasis enrolled in study
Safety/Tolerability
  • Safe and well-tolerated
  • Most common Adverse Events (AEs) were mild or moderate gastrointestinal (GI)-related events

Sources

Proprietary analysis based on IMS data.

CDC: Invasive Candidiasis.