1646. Combined Resistance Analyses from Phase 2b Studies of Presatovir Treatment in RSV-Infected Adults
Session: Oral Abstract Session: Respiratory and Gastroenteritis Viruses
Friday, October 5, 2018: 2:30 PM
Room: W 2002

Background:   Presatovir is an oral respiratory syncytial virus (RSV) fusion inhibitor in development for the treatment of RSV infection. Results from a healthy volunteer challenge study show that presatovir significantly reduced RSV viral load and clinical signs and symptoms. Here we present combined resistance analyses from four phase 2b studies in naturally RSV infected adults.

Methods:   RSV RNA was isolated from nasal swabs collected at baseline and post-baseline in studies GS-US-218-0108, GS-US-218-1502, GS-US-218-1227, and GS-US-218-1797. Full length RSV fusion (F) gene was PCR amplified and population sequencing was performed.

Results:   Of 233 presatovir-treated adults in the efficacy analyses, post-baseline resistance-associated substitutions were detected in 18 (7.7%) subjects. Frequencies of resistance development varied by study (Table 1). Resistance substitutions known to confer high-level (>200 fold) reduced susceptibility to presatovir detected in >1 subject were: T400I (n=6), S398L (n=3), L141F (n=2), and F140I (n=2) in F. Subjects with resistant virus had less viral load reduction than presatovir-treated subjects without resistant virus. Resistance development did not impact clinical outcomes. In study GS-US-218-0108, subjects with lymphopenia (<200 cells/μL) at baseline were significantly more likely to develop resistance substitutions.

Table 1. Resistance Development Frequencies in Phase 2b Studies

Study

Subject Population

Presatovir Dose

Presatovir-Treated Subjects in Efficacy Analysis, n

Subjects with Resistance- Associated Substitutions, n (%)

GS-US-218-0108

Hematopoietic cell transplant (HCT) recipients with upper respiratory tract infection

Days 1, 5, 9, 13, and 17: 200 mg

89

10 (11.2%)

GS-US-218-1502

HCT recipients with lower respiratory tract infection

Days 1, 5, 9, 13, and 17: 200 mg

29

6 (20.7%)

GS-US-218-1227

Hospitalized adults

Day 1: 200 mg

80

1 (1.3%)

GS-US-218-1797

Lung transplant recipients

Day 1: 200 mg
Days 2–14: 100 mg

35

1 (2.9%)

Conclusion:   Presatovir treatment resulted in varying rates of resistance development across four phase 2b studies. Resistance development impacted virologic response without affecting clinical outcomes. Differences among study populations and dosing regimens may have influenced rates of resistance development.

 

Danielle Porter, Ph.D., Ying Guo, Ph.D., Jason Perry, Ph.D., David Gossage, M.D., Timothy Watkins, M.D., Jason Chien, MD and Robert Jordan, Ph.D., Gilead Sciences, Inc., Foster City, CA

Disclosures:

D. Porter, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

Y. Guo, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

J. Perry, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

D. Gossage, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

T. Watkins, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

J. Chien, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

R. Jordan, Gilead Sciences, Inc.: Employee and Shareholder , Salary and stocks .

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