159: Pharmacokinetics, Pharmacodynamics & Safety of Budigalimab, An Anti-PD-1 Monoclonal Antibody, in People Living With HIV-1

Statement of Purpose, Innovation or Hypothesis: HIV-1 infection remains a major global health problem with antiretroviral therapy (ART)-free viral control remaining an unmet need. Programmed cell death protein 1 (PD-1) receptor blockade offers a promising approach to help address this. Budigalimab is a humanized, IgG1 L234A L235A monoclonal antibody targeting the PD-1 receptor, which was evaluated in two randomized placebo-controlled Phase 1b studies in people living with HIV-1 (PLWH) (NCT04799353 [Study 1] and NCT04223804 [Study 2]).This work summarizes pharmacokinetics (PK) and key pharmacodynamics (PD) and safety findings from these studies.

Description of Methods & Materials: Studies 1 and 2 assessed safety, PK and PD of budigalimab following single and multiple intravenous (IV) or subcutaneous (SC) doses in PLWH who were on suppressive ART or underwent planned analytical treatment interruption (ATI). In Study 1, participants on suppressive ART received single doses of 10 mg IV, 10 mg SC or 20 mg SC budigalimab. In Study 2, participants received two doses of 2 mg IV or 10 mg IV every four weeks (Q4W) or four doses of 10 mg IV every two weeks (Q2W), and were on suppressive ART or underwent planned ATI. PK data was evaluated using non-compartmental analyses. Dose-proportionality was investigated using an analysis of covariance (ANCOVA) of the log-transformed dose-normalized exposure metrics. Immunogenicity, and the percentage and duration of PD-1 receptor saturation (RS) were evaluated for all treatment arms.

Data & Results: In Study 1, exposures following 20 mg SC budigalimab were more than dose-proportional relative to 10 mg SC. SC bioavailability was approximately 53-62%. In Study 2, budigalimab exposures following 10 mg IV were more than dose-proportional relative to 2 mg IV, suggesting target-mediated drug disposition at the 2 mg IV dose level. Negligible drug accumulation of budigalimab was observed with a Q4W dosing interval at the 2 mg IV and 10 mg IV dose levels. Approximately 2-fold drug accumulation was observed with a Q2W dosing interval at the 10 mg IV dose. Across all IV groups in both studies, 19/39 participants were positive for anti-drug antibodies (ADA). In the 10 mg SC group, 5/8 participants were ADA-positive. No participants were ADA-positive in the 20 mg SC group. No apparent impact of ADA on budigalimab PK was observed across the IV groups, whereas a trend towards lower exposures due to ADA was observed in the 10 mg SC group. Nearly complete (≥95%) and sustained PD-1 RS was achieved for approximately 10 weeks with Q2Wx4 doses of 10 mg IV budigalimab. Based on exploratory analyses, efficacy signals were observed in a subset of participants (6/9) who received this regimen. Two Grade 1 and one Grade 2 non-serious reversible immune-related adverse events were reported in the two studies. No apparent exposure-safety relationships were identified from preliminary analyses.

Interpretation, Conclusion or Significance: PK/PD and safety data in Phase 1b demonstrate a favorable profile of budigalimab to continue development in Phase 2 in PLWH.

Disclosures: AbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. TRV, PK, AGPdS, TG, FZ, HB, MS and NMM are employees of AbbVie, Inc. and may own AbbVie, Inc. stock or stock options. MR is a speaker for AbbVie, Gilead Sciences, ViiV Healthcare, and Janssen and a consultant for Gilead Sciences, ViiV Healthcare, Merck, and Abbott. JPR is a speaker and consultant for AbbVie, Gilead Sciences, Merck & Co., Moderna, ViiV Healthcare.

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