Program Schedule

1574
Safety Profile of HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 24 Analysis

Session: Poster Abstract Session: HIV Treatment: Outcomes, Adherence, and Toxicities
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • Lalezari et al_IDSA 2014_Poster 1574_02-Oct.pdf (999.4 kB)
  • Background: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is an ongoing, Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose–response of BMS-663068 vs. atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive subjects (sbj). At Week 24, response rates across the BMS-663068 arms were consistent with ATV/r.

    Methods: Antiretroviral TE sbj (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (including BMS-626529 IC50<100 nM) were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control arm (ATV/r 300/100 mg QD), with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). The complete safety profile through Week 24 is reported.

    Results: In total, 251 sbj were treated (BMS-663068, 200; ATV/r, 51). No BMS-663068-related adverse events (AEs) led to discontinuation. Grade 2–4 drug-related AEs occurred in 17/200 (8.5%) sbj across the BMS-633068 arms; however, these events were mostly single instances and no dose-relationship was seen. Similarly, no noticeable trend for Grade 3–4 laboratory abnormalities was seen and Grade 3–4 hematologic changes and liver chemistry elevations were uncommon (neutropenia, 2.5%; AST/ALT elevations, 1% [n=196]). In the ATV/r arm, Grade 2–4 drug-related AEs occurred in 14/51 (27.5%) sbj and were mostly secondary to gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs) occurred in 13/200 (6.5%) and 5/51 (9.8%) sbj receiving BMS-663068 and ATV/r, respectively; most were secondary to infections and none were related to study drugs. The most common AE reported for BMS-663068 was headache (28/200, 14%), occurring in 5/51 (10%) sbj in the ATV/r arm; in the BMS-663068 arms this was not dose-related. There were no deaths.

    Conclusion: BMS-663068 was generally well tolerated across all arms, with no related SAEs or AEs leading to discontinuation and no dose-related safety signals. There were no trends for Grade 2–4 AEs or clinical laboratory abnormalities. These results support continued development of BMS-663068.

    Jacob Lalezari1, Gulam H Latiff2, Cynthia Brinson3, Juan Echevarría4, Sandra Treviño-Pérez5, Johannes R Bogner6, David Stock7, Samit R Joshi7, George J Hanna8, Max Lataillade7 and AI438011 study team, (1)Quest Clinical Research, San Francisco, CA, (2)Maxwell Clinic, Durban, South Africa, (3)Central Texas Clinical Research, Austin, TX, (4)Hospital Nacional Cayetano Heredia, Lima, Peru, (5)Mexico Centre for Clinical Research, Mexico City, Mexico, (6)Hospital of the University of Munich, Munich, Germany, (7)Bristol-Myers Squibb, Wallingford, CT, (8)Bristol-Myers Squibb, Princeton, NJ

    Disclosures:

    J. Lalezari, None

    G. H. Latiff, None

    C. Brinson, Bristol-Myers Squibb: Investigator, Central Texas Clinical Research received monies for conducting the trial
    Gilead: Board Member and Speaker, sit on advisory board, sit on education board, personal fees
    Boehringer Ingelheim: Investigator, Contract Principal Investigator for clinical trials
    Bristol-Myers Squibb: Investigator, Contract Principal Investigator for clinical trials
    ViiV: Investigator, Contract Principal Investigator for clinical trials
    GlaxoSmithKline: Investigator, Contract Principal Investigator for clinical trials
    Gilead: Investigator, Contract Principal Investigator for clinical trials
    Shionogi: Investigator, Contract Principal Investigator for clinical trials
    AstraZeneca: Investigator, Contract Principal Investigator for clinical trials
    Pfizer: Investigator, Contract Principal Investigator for clinical trials
    Janssen: Investigator, Contract Principal Investigator for clinical trials
    Sangamo: Investigator, Contract Principal Investigator for clinical trials
    Taimed: Investigator, Contract Principal Investigator for clinical trials
    Theratechnologies: Investigator, Contract Principal Investigator for clinical trials
    Serono: Investigator, Contract Principal Investigator for clinical trials
    Achillion: Investigator, Contract Principal Investigator for clinical trials

    J. Echevarría, Bristol-Myers Squibb: Grant Investigator, Grant recipient

    S. Treviño-Pérez, Bristol-Myers Squibb: Grant Investigator, Grant recipient

    J. R. Bogner, All companies involved in antiretroviral therapy: Speaker's Bureau, Speaker honorarium

    D. Stock, Bristol-Myers Squibb: Employee and Shareholder, Salary

    S. R. Joshi, Bristol-Myers Squibb: Employee and Shareholder, Salary

    G. J. Hanna, Bristol-Myers Squibb: Employee and Shareholder, Salary

    M. Lataillade, Bristol-Myers Squibb: Employee and Shareholder, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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