H-891. A Phase 2 Safety and Efficacy Study of Bevirimat (BVM) in Heavily Treatment Experienced HIV+ Patients Identifies the Target Phase 3 Study Profile
Session: Slide Session: Antiretroviral Therapy
Sunday, October 26, 2008: 12:00 AM
Room: Independence A (Grand Hyatt)
Background: BVM is a novel HIV-1 maturation inhibitor targeting the Gag capsid SP-1 cleavage site. A prior 10 day study showed a 1 log viral load reduction (VLR) in patients given BVM 200mg QD. A separate retrospective analysis showed that patients without key baseline Gag polymorphisms at Q369, V370 or T371 were more likely to respond to BVM. Methods: In a Phase 2 double-blind, randomized dose escalation study, 59 treatment-experienced patients with >1 primary resistance mutation received 2 weeks of BVM or placebo as functional monotherapy on top of a failing (VL >2000 copies/mL) background regimen. Patients initially received a 400mg BVM tablet dose, or placebo; in the modified study, patients received a 250, 300, 350 or 400mg BVM liquid dose, or placebo. Results: Of 44 patients given the assigned BVM dose, the mean VL change was -0.6 log copies/mL (+0.05 log for 13 patients given placebo); 12/13 (92%) patients with BVM trough levels >20 ug/mL and without the key Gag polymorphisms had a VLR >0.5 log; 10/13 (77%) had a VLR >1.0 log (group mean VLR: -1.26 log). 32/46 (70%) BVM treated patients and 10/13 (77%) placebo treated patients had >1 adverse event (AE). For BVM and placebo treated patients respectively, the most common AEs were diarrhea (22%; 39%), nausea (20%; 31%) and headache (20%; 23%); all were Grade 1. For BVM and placebo treated patients respectively, the most common lab changes were: glucose (13%; 8%), total cholesterol (11%, 15%) and triglycerides (9%, 15%); nearly all were Grade 2. Conclusion: Through 2 weeks BVM and placebo were similarly well tolerated, and responder patients with BVM troughs >20 ug/mL had a high magnitude VLR of 1.26 log. Planned Phase 3 studies will employ these criteria to confirm the utility of BVM in treatment-experienced patients.
Calvin Cohen, MD, MSc1, Cynthia Brinson2, David Martin3, Gary Richmond, MD, FACP, FCCP4, Jacob Lalezari, MD5, Maria Gigliotti6, Melanie Thompson, MD7, Richard Elion8, Scott McCallister6 and  J. Lalezari,
Merck Role(s): Investigator, Received: Research Support.
Glaxo SmithKline Role(s): Investigator, Received: Research Support.
Tibotec/JNJ Role(s): Investigator, Received: Research Support.
Boehringer Ingelheim Role(s): Investigator, Received: Research Support.
Panacos Role(s): Investigator, Received: Research Support.
Pharmasset Role(s): Investigator, Received: Research Support.
Pfizer Role(s): Investigator, Received: Research Support.
Roche Role(s): Investigator, Received: Research Support.
Koronis Role(s): Investigator, Received: Research Support.
Progenics Role(s): Investigator, Received: Research Support., (1)Comunity Research Initiative of New England, Boston, MA, (2)CTCR, (3)Panacos, Gaithersburg, MD, (4)North Broward Hospital District,, Ft. Lauderdale, FL, (5)Quest Clinical Research, San Francisco, CA, (6)Panacos, (7)ARCA, (8)Whitman Walker Clin.

BIOGRAPHICAL SKETCH
CALVIN J. COHEN, MD, MSc
Research Director
Community Research Initiative of New England and
Harvard Vanguard Medical Associates
Calvin J. Cohen, M.D., M.Sc., is the Research Director of Community Research Initiative of New England. In addition, he is the Research Director of Harvard Vanguard Medical Associates, a Clinical Instructor at Harvard Medical School, and Staff Physician at Brigham and Women's Hospital.
Dr. Cohen earned his B.A. degree at Cornell University, his M.D. at the Albert Einstein College of Medicine, and his M.Sc. at the Harvard School of Public Health. After graduating, he completed his internship and residency in medicine at Beth Israel Hospital in Boston. He also served as Chief Medical Resident at the Veterans Administration Hospital in Brockton, Massachusetts, under the auspices of Harvard Medical School. His fellowship in general internal medicine was completed at Harvard Medical School.
Dr. Cohen's research interests include the study and antiviral treatment of HIV/AIDS and related topics. He has served as co-chair of the Scientific Advisory Committee of the AmFAR Community-Based Clinical Trial Network and was a co-investigator of the Harvard AIDS Clinical Trial Unit. In addition to his clinical and research roles, Dr. Cohen is currently a member of the Executive Committee of the INSIGHT network, an NIH-supported network of clinician-researchers. He is also a co-Principal Investigator of the New England AIDS Education and Training Center.
Dr. Cohen has authored and co-authored numerous articles on HIV/AIDS and related topics. His articles are published in Annals of Internal Medicine, New England Journal of Medicine, and Lancet. Dr. Cohen is recipient of the Outstanding Physician's Award for his work at Harvard Vanguard Medical Associates; the Harvard Pilgrim Health Care - Robert H. Ebert Teaching Award and the Champions of the Search Award; the Community Recognition Award of the AIDS Action Committee of Massachusetts; the Distinction for Research in Cardiology, Albert Einstein College of Medicine; and the Upjohn Award for Excellence in Medical Training.

Dr. Kotler is Professor of Medicine at Columbia University College of Physicians and Surgeons and is the Chief of the Division of Gastroenterology and Liver Disease at St. Luke's-Roosevelt Hospital. He earned his medical degree at the Albert Einstein College of Medicine.
Donald P. Kotler, MD is an investigator in the fields of nutritional and gastrointestinal disease. A pioneer in the study of the AIDS wasting syndrome, Dr. Kotler has concentrated on the study of body composition in order to define the characteristics of malnutrition in HIV infection and other diseases, as well as strategies to reverse the wasting process. He has been the Principal investigator on single site and mult-center studies of nutritional therapies for HIV-associated malnutrition. In addition, Dr. Kotler has studied the opportunistic enteric complications of AIDS as well as the role of HIV as an enteric pathogen. More recently, he has studied the body composition adn metabolic abnormalities, termed lipodystrophy, that occur in HIV-infected patients on highly active antiretroviral therapy, and is applying his knowledge and laboratory techniques to the study of chronic liver disease. Dr. Kotler has worked collaboratively with a number of investigators at the National Institutes of Health and other research organizations. He has served as a mentor for three doctoral candidates and many GI fellows. He has worked with several national and international groups including the International AIDS Society-USA, NIH Office of AIDS Research Planning Committees, the International Association of Physicians in AIDS Care and others. He is Vice President of the Board of Directors of ACRIA, a Trustee of the Royal S. Marks Foundation, a member of the Board of Directors of the National Center for the Study of Wilson's Disease, and a member of the Medical Advisory Board fo the WIlson's Disease Association of America.

Dr. Jacob P. Lalezari, M.D., is the Director of Quest Clinical Research and an Assistant Clinical Professor of Medicine at UCSF/Mount Zion Hospital. Since 1989, Dr Lalezari has served as a Principal Investigator for phase I, II, and III clinical studies of new therapies for viral diseases including HIV/AIDS, CMV, HPV, HSV, Hepatitis B &C, Influenza, and RSV. In 1997, he became CEO and Director of Quest Clinical Research.

Dr. Thompson has been involved in HIV research as Principal Investigator of the AIDS Research Consortium of Atlanta (ARCA) since 1988. ARCA is a community-based research center involving over 50 private doctors and 5 public clinics in Atlanta. She has served as principal investigator on over 300 clinical trials of therapies to treat HIV and its complications and has served on national HIV guidelines panels since 1989, including the IAS-USA Antiretroviral Guidelines Panel since its inception. She is a former chair and current member of the National Institutes of Health, Office of AIDS Research Therapeutics Research Working Group.
She has become increasingly involved in HIV prevention research over the last few years and currently is one of three principal investigators for the CDC-sponsored US study of tenofovir for HIV prevention in HIV-negative men who have sex with men. She also has conducted two large studies of HIV prevention with persons who are HIV-positive. Currently she is principal investigator of a CDC-sponsored study testing strategies for African-American men who have sex with men. Dr. Thompson oversees ARCA’s Metro Atlanta Women of Color Initiative (MAWOCI) and Synergy Atlanta projects. Both are mobile community outreach programs offering free HIV rapid testing and/or STD testing, prevention education and linkage to care. Dr. Thompson has recently been an advisor to the AIDS Personal Public Service Announcement Project, a joint venture of the New Media Institute of the University of Georgia and Verizon Communications.
Most importantly, she is actively involved in the primary care of persons with HIV infection in Atlanta, from whom she derives the passion and inspiration for her ongoing work in HIV research.



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