Invasive Fungal Disease Treatment, Rezafungin, Moves to Phase 3 Trials

Cidara Therapeutics has announced that it will be presenting findings at the 2018 Hot Topics in Infectious Diseases (HTIDE) Conference from studies evaluating its novel antifungal agent, rezafungin, for the treatment of patients with aspergillosis and invasive candidiasis.

In its recent Fungal Disease Awareness Week, the Centers for Disease Control and Prevention (CDC) noted that people in the United States and around the world can suffer from undiagnosed fungal diseases, leading to potential illness and death. While mild skin rashes are a common side effect of infections from fungi found in the environment, humans can experience flu-like illness from fungal infections along with life-threatening fungal meningitis and bloodstream infections. Individuals on chemotherapy for cancer, organ transplant recipients, hospitalized patients, and those living with HIV/AIDS have weakened immune systems and are, therefore, at greater risk of getting fungal infections.

In March 2018, the biotechnology company Cidara released data on phase 1 and phase 2 clinical trials for the drug rezafungin, a novel antifungal echinocandin, showing positive safety and efficacy results for 2 dosing regimens. In those trials, investigators found that both regimens provided therapeutic exposures substantially above those that are needed to eradicate Candida infections. Cidara notes that rezafungin is the only once-weekly antifungal product candidate in development for the treatment and prevention of life-threatening invasive fungal infections. In a recent statement, Cidara announced that new data from its studies on rezafungin will be presented in 3 abstracts at the upcoming HTIDE Conference in Venice, Italy, to be held from October 25 to 26, 2018.

Of the 3 abstracts being presented at the upcoming bi-annual conference, 2 highlight results from Cidara’s phase 2 STRIVE trial and will include analyses of rezafungin in special patient populations and by geographic outcomes. The third presentation will cover results on the in vivo efficacy of rezafungin in aspergillosis. Rezafungin is unique in that it has a has a prolonged half-life and front-loaded plasma exposure which allows for once-weekly intravenous therapy, setting it apart from other echinocandins. Current studies on the drug are focused on addressing the lack of effective treatment options for candidemia and invasive candidiasis as well as for the prevention of invasive fungal infections caused by Candida, Aspergillus and Pneumocystis in patients undergoing allogeneic bone marrow transplantation.

In an interview with Contagion^®, Cidara chief medical officer, Taylor Sandison, MD, MPH, explained how rezafungin’s potential approval can impact health care. “If approved, rezafungin has the opportunity to immediately fill a number of unmet needs,” he explained. “For the treatment of invasive Candida infections, the high, front-loaded exposure and improved tissue distribution compared to other echinocandins mean that rezafungin may be the best choice for subjects with deep tissue infections.

He added that the once-weekly dosing may allow for early discharge from the hospital, while maintaining first-line therapy for Candida instead of being forced to step down to azole treatment, which, according to Dr. Sandison, is inferior.

“For prevention of invasive fungal disease in blood and marrow transplant patients, rezafungin would provide a once-weekly option for prophylaxis that can cover the 3 most common causes of invasive fungal disease—Candida, Aspergillus, and Pneumocystis infections—with lower risks of toxicity and drug-drug interactions than the current 2-drug standard of care,” Dr. Sandison added.

There are 2 upcoming phase 3 trials for rezafungin. The first, known as ReSTORE, will compare the treatment of candidemia and invasive candidiasis with once-weekly rezafungin versus once-daily caspofungin. The second, ReSPECT, will compare outcomes in the prevention of invasive fungal disease in subjects undergoing allogeneic blood and marrow transplantation between rezafungin and either fluconazole or posaconazole and trimethoprim-sulfamethoxazole.