The development of a monoclonal antibody (mAb) as a long-acting, single-agent maintenance therapy (SAMT) represents a major milestone in the treatment of HIV-1 infection. PRO 140 (humanized CCR5 mAb) demonstrates potent antiviral activity as a SAMT for >4 years as a weekly subcutaneous injection (SC) in patients infected exclusively with CCR5-tropic HIV-1 (Dhody, K. et al. (2018). HIV Clin Trials 19(3):85-93). In addition, PRO 140 presents a high genetic barrier to block HIV-1 entry, favorable tolerability, and limited drug-drug or -food interactions.
PRO 140_CD03 (N=350) is a three part, phase 2 study enrolling virally suppressed HIV-1 patients with CCR5-tropic HIV-1 receiving combination antiretroviral (cART) therapy. Patients received weekly doses of PRO 140 on SAMT following one week of overlap of the existing cART regimen that is then discontinued. In part 1, 156 participants received 350 mg PRO 140 SC in a single-arm design. In part 2, 147 participants received 350 or 525 mg PRO 140 SC in a 1:1 ratio as randomized controlled, two-arm study. In an ongoing part 3, 47 participants are to be randomized to receive 525 or 700 mg PRO 140 SC in a 1:1 ratio.
Of the 327 patients enrolled, median age was 51 yrs (21-77) with the majority reported as male (79%) and 37% were non-white. On average, participants were diagnosed with HIV-1 infection for 16.8 yrs and were on cART regimen for 14.8 yrs. This abstract focuses on preliminary results from patients randomized 1:1 to 350 mg (N=73) or 525 mg (N=74) PRO 140 SC on SAMT. While the study is ongoing, a key interim finding from 147 patients (4-48 weeks on SAMT) indicate that an odds ratio of 4.43 for the virologic response rates with 525 mg compared with 350 mg PRO 140 SC. Virologic failure is defined as two consecutive plasma HIV-1 RNA levels of ≥200 c/mL. The frequency and severity of injection site reactions were comparable between the three dose groups and the incidence or severity of injection site reactions was not increased in patients receiving higher doses. Overall, PRO 140 SC was generally well tolerated at all dose levels in this study.
Higher doses of PRO 140 SC are required to maintain virologic suppression on SAMT in the majority of patients infected exclusively with CCR5-tropic HIV-1. After testing both 350 mg and 525 mg, 700 mg of weekly PRO 140 SC is currently underway and will be presented. PRO 140 SC has the potential as a SAMT for long-term suppression of HIV-1 replication.