1718. Rezafungin Clinical Safety and Efficacy in Patients with Candidemia and/or Invasive Candidiasis in the Randomized, Double-blind, Multicenter, Phase 2 STRIVE Study
Session: Oral Abstract Session: Clinical Trials that May Change Your Practice
Saturday, October 6, 2018: 9:30 AM
Room: S 158

Background: STRIVE was conducted to assess the safety and efficacy of rezafungin (RZF), a novel echinocandin with pharmacokinetics allowing once weekly dosing and high, front-loaded plasma drug exposure, and to help determine dosing for a Phase 3 study.

Methods: Adults (≥18y) with mycologically-confirmed candidemia and/or invasive candidiasis (IC) were randomized (1:1:1) to receive RZF IV for up to 4 weeks dosed at either 400mg weekly (Group 1) or 400mg on week 1 and 200mg weekly thereafter (Group 2), or standard of care (SOC; daily caspofungin [CSP] with optional criteria-defined oral stepdown after ≥3 days of IV therapy; Group 3). Safety and efficacy were evaluated by treatment-emergent adverse events (TEAEs) and overall success at day 14 (1° endpoint; clinical cure + mycological success), investigator assessment of clinical cure, mycological success (in subjects with candidemia only), overall success in IC subjects only, and mortality. Outcomes at day 5 were also assessed.

Results: The rate of TEAEs was 88.6% in Group 1, 94.4% in Group 2, and 81.8% in Group 3. Severe AEs occurred in 37.1%, 27.8%, and 39.4% of the groups, respectively. There were no concerning trends in System Organ Class groups, specific AEs, or laboratory abnormalities. The most common Candida species isolated was C. albicans (n=45), followed by C. glabrata (n=17), C. tropicalis (n=15), and C. parapsilosis (n=13). A high number of indeterminate responses due to missing data points in Group 1 led to analyses including and excluding the indeterminate responses. Overall, clinical, and mycological response rates at day 14 are shown in Table 1. Overall response at day 5 (Table 2) was highest in the RZF 400mg/200mg group, followed by the RZF 400mg/400 mg and SOC groups. The overall mortality rate was 15.2% in Group 1, 9.7% in Group 2, and 17.9% in Group 3.

Conclusion: RZF demonstrated safety and efficacy comparable to CSP in the treatment of candidemia/IC. There were no concerning trends in AEs. The efficacy rates were similar among all three treatment groups, trending higher with the RZF 400mg/200mg regimen on most efficacy outcomes, though the sample size is small and confirmation of these findings is required in a larger Phase 3 clinical trial. These findings support further clinical study of RZF in Phase 3.

George R Thompson, MD1, Jose Vazquez, MD, FACP, FIDSA2, Alex Soriano, MD, PhD3, Athanasios Skoutelis, MD4, Luis Ostrosky-Zeichner, MD, FIDSA, FSHEA5, Karen Mena, BA6, Laura Navalta, BA6, Taylor Sandison, MD, MPH6 and Peter Pappas, MD7, (1)Division of Infectious and Immunologic Diseases, University of California - Davis, Sacramento, CA, (2)Infectious Diseases, Augusta University Medical Center, Augusta, GA, (3)Infectious Diseases, Hospital Clínic, University of Barcelona, Barcelona, Spain, (4)Evangelismos General Hospital, Athens, Greece, (5)Internal Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, (6)Cidara Therapeutics, San Diego, CA, (7)Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL

Disclosures:

G. R. Thompson, Cidara: Investigator , Research support . Mayne: Investigator , Research support . Astellas: Consultant and Investigator , Consulting fee and Research support . Scynexis: Investigator , Research support . Vical: Consultant , Consulting fee .

J. Vazquez, None

A. Soriano, Cidara Therapeutics, Inc.: Investigator , Research grant .

A. Skoutelis, None

L. Ostrosky-Zeichner, Cidara Therapeutics: Grant Investigator , Research grant .

K. Mena, Cidara Therapeutics: Employee , Salary .

L. Navalta, Cidara Therapeutics, Inc.: Employee , Salary .

T. Sandison, Cidara Therapeutics: Employee , Salary .

P. Pappas, Cidara Therapeutics: Consultant and Grant Investigator , Research grant . IMMY: Consultant and Grant Investigator , Research grant . Scynexis: Consultant and Grant Investigator , Research grant . Gilead: Grant Investigator , Research grant .

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.