- VL-2397 appeared safe and well-tolerated with favorable pharmokinetic profile in healthy subjects
- Phase 2 initiation is planned for the fourth quarter of 2017
SAN DIEGO, June 05, 2017 (GLOBE NEWSWIRE) -- Vical Incorporated (Nasdaq: VICL ) announced that the company presented clinical data from its completed first-in-human Phase 1 trial of its novel antifungal, VL-2397 at the American Society of Microbiology (ASM) Microbe 2017 meeting in New Orleans. The results indicate that VL-2397 appeared to be safe and well tolerated with favorable plasma pharmacokinetic (PK) profiles in healthy subjects. Vical is planning to initiate a Phase 2 trial in patients with invasive aspergillosis in the fourth quarter of 2017.
Mammen “Anza” P. Mammen, Jr., M.D., Vical’s Senior Vice President, Clinical Development, presented the poster, “Phase 1 Safety and Pharmacokinetics Study of VL-2397, a Novel Antifungal Agent.” The Phase 1 trial of VL-2397, was a randomized, double-blind, placebo-controlled trial designed to evaluate safety, tolerability and PK of single and multiple ascending doses of intravenous VL-2397 in healthy volunteers. A total of 96 subjects ranging in age from 19 to 55 were enrolled into 11 cohorts; subjects completed all study visits.
Safety findings revealed neither treatment-related serious adverse events nor Grade 4 Treatment-Emergent Adverse Events (TEAEs) at any dose. The most common TEAEs were infusion site reactions. Dosing in two subjects was discontinued after dose 2 in the highest once-daily (1200 mg) dose cohort due to Grade 3 generalized rash (the only Grade 3 AE in the trial) and Grade 1 creatinine elevation, respectively. VL-2397 appeared to be well tolerated up to the 1200 mg dose. The PK analysis demonstrated low variability between subjects within a cohort and between cohorts receiving the same dose. No VL-2397 accumulation was observed with any dose, including the final cohort with dosing of 300 mg every 8 hours for 7 days followed by 600 mg daily for 21 days.
“Invasive aspergillosis is a very serious fungal infection involving the lungs and other organs in susceptible hosts, and it is associated with a high mortality rate. Current therapies can have toxicities and cause drug interactions, and response rates are often suboptimal,” said Peter G. Pappas, M.D., F.A.C.P., Director of the Mycoses Study Group and Professor of Medicine in the Division of Infectious Diseases and Department of Medicine at the University of Alabama in Birmingham. “New treatment options are urgently needed for these patients. The profile of VL-2397 emerging from Phase 1 is encouraging, so if safety and efficacy can be demonstrated in patients with invasive aspergillosis in Phase 2, it could be very promising.”
Additionally, Laura Kovanda from Astellas Pharma Inc. and the University of Liverpool presented the poster, “Population Pharmacokinetic Modeling of VL-2397, a Novel Systemic Antifungal Agent: Analysis of a Single and Multiple Dose Phase 1 Study.” The PK from single and multiple ascending dose cohorts in the Phase 1 study of VL-2397 were combined to construct a population PK model. A total of 1462 plasma samples from 64 subjects were included. The data indicate that VL-2397 has non-linear saturable binding kinetics. Height was the only covariate with a significant relationship to clearance. The PPK model can be used to optimize dosing by bridging the kinetics to efficacious pharmacodynamic targets.
VL-2397 was also featured in an oral presentation and two additional poster presentations at the conference. The abstracts are available through the conferences online program planner:
- Sean Sullivan, Ph.D. Vical’s Senior Executive Director, Pharmaceutical Sciences, will presented “Development of VL-2397 as a Novel Antifungal Drug Candidate to Treat Invasive Aspergillosis,” providing an overview of the product profile, lead indication, preclinical data and the Phase 1 trial. The slides presented by Dr. Sullivan will be made available on Vical’s website.
- Dr. Sullivan also presented the poster, “Characterization of Potential Drug Interactions and Off-Target Activities of VL-2397, a Novel Antifungal Agent against Invasive Aspergillosis.” Results of these studies suggest that VL-2397 has a low propensity for drug-drug interactions because it does not tend to exert a time-dependent inhibitory effect on the CYP isozymes tested, and at the drug exposure levels tested, appears to have a very low potential for off-target activity with a variety of cellular proteins. This is consistent with VL-2397’s novel Sit1-dependent mechanism of action and suggest it may provide an effective therapeutic option for treating patients with invasive aspergillosis.
- Nathan Wiederhold, Pharm.D. from the University of Texas Health Science Center San Antonio, presented the poster, “The Novel Antifungal VL-2397 Demonstrates Efficacy in an In Vivo Model of Invasive Candidiasis Caused by Wild-Type and Multi-Drug Resistant Candida glabrata .” In this NIH-sponsored in vivo study, VL-2397 demonstrated efficacy in an experimental model of invasive candidiasis caused by C. glabrata . Its efficacy, as measured by reductions in kidney fungal burden, was evident against infections caused by both wild-type and multi-drug resistant isolates. The results demonstrate the therapeutic potential of VL-2397 against invasive C. glabrata infections.
The FDA has granted Vical Qualified Infectious Disease Product (QIDP), Orphan Drug and Fast Track designations for VL-2397 in the treatment of invasive aspergillosis. Under the QIDP designation Vical has been able to interact regularly with the FDA on the Phase 2 trial design and a potential expedited development pathway for VL‑2397.
About Vical Vical develops biopharmaceutical products for the prevention and treatment of chronic or life-threatening infectious diseases, based on its patented DNA delivery technologies and other therapeutic approaches. Additional information on Vical is available at www.vical.com .
Forward-Looking Statements This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include anticipated developments in clinical programs, including the plans, timing of initiation, and enrollment for clinical trials. Risks and uncertainties include whether Vical or others will continue development of VL-2397; whether Vical will be able to obtain regulatory allowances or guidance necessary to proceed with proposed clinical trials or implement anticipated clinical trial designs; whether on-going or planned clinical trials will be initiated or completed on the timelines Vical currently expects, whether any product candidates will be shown to be safe and efficacious in clinical trials; whether Vical will have access to sufficient capital to fund its planned development activities; whether Vical will seek or gain approval to market any product candidates; and additional risks set forth in the Company's filings with the Securities and Exchange Commission. These forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements.
Contact: Andrew Hopkins (858) 646-1127 Website: www.vical.com
