Pipeline Asset Update for BMS-663068 (attachment inhibitor)
Pipeline Asset: BMS-663068 is an HIV-1 attachment inhibitor in development for the treatment of HIV-1 infection
Current Phase of Development: Phase IIa
Meeting or Publication:

Conference on Retroviruses and Opportunistic Infections (CROI)
Study Title: Pharmacodynamics, Safety, and Pharmacokinetics of BMS-663068, a Potentially First in Class Oral HIV Attachment Inhibitor
Abstract Number: 49
Date/Time of Presentation: February 28, 2011 from 10:45 – 11:00 a.m. EST
Study Objective: To evaluate the pharmacodynamics, safety and pharmacokinetics of BMS-663068 in subtype B HIV-1 infected subjects.
Study Conclusion: Short-term monotherapy dosing of BMS-663068 for 8 days in HIV-1-infected subjects resulted in a substantial decline in plasma HIV-1 RNA, or viral load, with increases in CD4+ cells.

BMS-663068 was found to be generally well tolerated in this study.

The pharmacokinetics (PK) profile of BMS-663068 supports once or twice daily dosing with or without ritonavir in patients with susceptible virus.

Longer term clinical trials of BMS-663068 as part of a combination antiretroviral regimen are warranted.

Efficacy Results: Five treatment groups were evaluated in this study.
  • Group A: BMS-663068 600 mg/ritonavir 100 mg, twice daily.
  • Group B: BMS-663068 1200 mg/ritonavir 100 mg, once daily.
  • Group C: BMS-663068 1200 mg/ritonavir 100 mg, twice daily.
  • Group D: BMS-663068 1200 mg twice daily, plus 100 mg ritonavir with the morning dose of BMS-663068.
  • Group E: BMS-663068 1200 mg, twice daily.

    The response rates and PK results for all five treatment groups are as follows:

    Group A
    n=10

    Group B
    n=10

    Group C
    n=10

    Group D
    n=10

    Group E
    n=10

    Median Maximal Change in HIV RNA log10 from Baseline
    (range)

    1.6
    (1.0 to 2.0)

    1.6
    (1.0 to 2.4)

    1.8
    (1.2 to 2.1)

    1.6
    (0.3 to 2.3)

    1.2
    (0.4 to 2.6)

    Median Day 8 Change in CD4 T-cell count at Day 8 versus baseline (range)

    130
    (-299 to 474)

    86
    (-33 to 240)

    102
    (-77 to 281)

    38
    (-241 to 259)

    23
    (-98 to 276)

    Geometric Mean Day 8 AUC ng•h/ml (CV%)

    26772 (49)

    22946 (44)

    60624 (27)

    55170 (36)

    42589 (21)

    Geometric Mean Day 8 Cmin ng/ml (CV%)

    438
    (68)

    55
    (101)

    749
    (56)

    613
    (62)

    524
    (57)

Adverse Events:

There were no clinically relevant effects on ECGs, laboratory values, vital signs, or physical exams.

AEs were mainly mild in severity; all AEs were grade 1 or 2. The most frequent AEs included headache (22 of 50, 44%) and rash (8 of 50, 16%).

There were no serious AEs or discontinuations of BMS study drugs or deaths due to AEs.
BMS-663068 Background:

BMS-663068 is an investigational, oral HIV-1 attachment inhibitor. BMS-663068 is a prodrug for BMS-626529 which binds to the viral envelope glycoprotein gp120 and interferes with attachment of the virus to the cellular CD4 receptor.

BMS-663068 is one of several molecules Bristol-Myers Squibb is studying for the potential treatment of HIV-1 infection. The portfolio of investigational compounds, which also includes a next-generation nucleoside reverse transcriptase inhibitor (NRTI) called festinavir, fits into the company's overall R&D focus on diseases where there is unmet medical need.

On February 16, 2011, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb's request of Fast Track designation for BMS-663068.
Study Background:

This randomized, open-label, multiple dose Phase IIa study enrolled HIV-1, subtype B infected subjects who were either antiretroviral naïve or antiretroviral experienced (but had not been on antiretroviral therapy for at least eight weeks).

The 50 subjects in this study were randomized to one of five treatment groups:

  • Group A: BMS-663068 600 mg/ritonavir 100 mg, twice daily
  • Group B: BMS-663068 1200 mg/ritonavir 100 mg, once daily
  • Group C: BMS-663068 1200 mg/ritonavir 100 mg, twice daily
  • Group D: BMS-663068 1200 mg twice daily, plus 100 mg ritonavir with the morning dose of BMS-663068
  • Group E: BMS-663068 1200 mg, twice daily

Key Inclusion Criteria:

  • Men and women, 18 years-old or older
  • HIV-1 infection, subtype B
    • Plasma HIV-1 RNA ≥ 5,000 copies/mL
    • CD4+ lymphocyte ≥ 200 cells/ μL
    • Antiretroviral naïve or experienced
    • Off all antiretroviral therapy for > 8 weeks
  • BMI of 18 to 35 kg/m2, inclusive

Key Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Any clinically significant abnormality on physical examination, vital signs, ECG or clinical laboratory determination at screening or prior to dosing
  • Evidence of active hepatitis B or C infection
ClinicalTrials.gov Identifier: NCT01009814
Request for More Information and Media Interviews: Investors: John Elicker, 609-252-4611, john.elicker@bms.com
Media: Cristi Barnett, 609-252-6028, cristi.barnett@bms.com
Supporting information: The abstract and the oral presentation can be viewed on the CROI website.