BMS-955176Other Names: BMS-176 Drug Class: Maturation Inhibitors Registry Number: S900006910 (ChemID) Organization: ViiV Healthcare Phase of Development: Phase II
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and GlaxoSmithKline press release3)
What is an investigational drug?
Anis one that is under study and is not approved by the U.S. (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is BMS-955176?
BMS-955176 is an investigational drug that is being studied for the treatment of HIV.
BMS-955176 belongs to a class (group) of HIV drugs called maturation inhibitors.2 Maturation inhibitors act during the last step of the HIVto prevent HIV from multiplying and infecting other cells.
At the beginning of the last step in the HIV life cycle, the newly formed HIV particles are still immature and can't infect other cells in the body. In this form, HIV has long chains of proteins that need to be cut into smaller proteins. The smaller HIV proteins can then combine to form mature HIV that is capable of infecting other cells. An HIVcalled breaks up the long chains into the smaller HIV proteins. (An enzyme is a protein that starts or increases the speed of a chemical reaction.)
Maturation inhibitors bind to a specific long HIV protein chain called Gag. Thisblocks protease from breaking up the Gag protein chain into smaller HIV proteins. Without the smaller HIV proteins, HIV cannot change into its mature, form. Instead, HIV remains immature and not infectious, preventing the from multiplying and reducing the amount of HIV in the body.4-6
The very first maturation inhibitor that was tested in clinical trials was called bevirimat. Bevirimat did not work well on HIV that had certain naturally occurring genetic variations, which are also called polymorphisms.studies have shown that BMS-955176 works better than bevirimat against some types of HIV with certain polymorphisms. (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.)7-10
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.11
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.11
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase IIIto be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.11
In what phase of testing is BMS-955176?
BMS-955176 is currently being studied in Phase II clinical trials.2
What are some studies on BMS-955176?
Study Names: AI468-002; NCT01803074
Sponsor: Bristol-Myers Squibb
Location: Germany and South Africa
Participants: Participants were HIV-infected adults with B virus and subtype C virus. Some participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had taken HIV medicines previously (also called ). Those who were treatment-experienced had never taken a protease inhibitor or maturation inhibitor before.
Purpose: The purpose of this study was to evaluate the safety and activity of BMS-955176.12,13
Study Names: AI468-048; NCT02386098
Sponsor: Bristol-Myers Squibb
Location: Multiple countries, including United States
Participants: Participants are HIV-infected, treatment-experienced adults. Participants had previous treatment failure with one or two (ART) regimens that included HIV medicines from two or three different HIV drug classes. (Treatment failure is when an ART regimen is unable to control HIV infection.)
Purpose: The purpose of this study is to look at the safety and effectiveness of BMS-955176.14
Study Names: AI468-038; NCT02415595
Sponsor: Bristol-Myers Squibb
Location: Multiple countries, including United States
Participants: Participants are HIV-infected, treatment-naive adults with levels (the amount of HIV in a blood sample) of at least 1000 copies/mL. Participants also have CD4 counts of more than 200 cells/mm3. (A is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function. The CD4 count of a healthy person ranges from 500 to 1600 cells/mm3.)
Purpose: The purpose of this study is to find a safe and effective of BMS-955176 for treatment-naive adults.15
For more details on the studies listed above, see the Health Professional version.
What side effects might BMS-955176 cause?
In the Phase IIa study discussed under the previous question (NCT01803074), diarrhea that was mild to moderate in severity was more common in participants with subtype B virus who were taking BMS-955176 than in participants taking . (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) The most frequently reported side effects among the treatment and placebo groups were headache and abnormal dreams in patients with subtype B virus and headache and constipation in patients with subtype C virus.13,16 In another part of the study, in which three of the four treatment groups received BMS-955176, the most common side effects in patients with subtype B virus were increased levels, headache, and abnormal dreams.16
Because BMS-955176 is still being studied, information on possible side effects of the drug is not complete. As testing of BMS-955176 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying BMS-955176?
More information about BMS-955176-related research studies is available from the AIDSinfo database of study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
How can I find more information about participating in a clinical trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.8
Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/S900006910. Last accessed on September 23, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on September 23, 2016.
- GlaxoSmithKline: Press Release, dated February 22, 2016. GSK’s global HIV business ViiV Healthcare completes transactions to acquire Bristol-Myers Squibb’s R&D HIV assets. Available at: http://www.gsk.com/en-gb/media/press-releases/2016/gsk-s-global-hiv-business-viiv-healthcare-completes-transactions-to-acquire-bristol-myers-squibb-s-randd-hiv-assets/. Last accessed on September 23, 2016.
- Adamson CS. Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process. Mol Biol Int. 2012;2012:604261. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410323/. Last accessed on September 23, 2016.
- Sundquist WI, Kräusslich HG. HIV-1 Assembly, Budding, and Maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385941/. Last accessed on September 23, 2016.
- Brown KC, Paul S, Kashuba AD. Drug Interactions with New and Investigational Antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857544/. Last accessed on September 23, 2016.
- Hwang C, Schürmann D, Sobotha C, et al. Second-Generation HIV-1 Maturation Inhibitor BMS-955176: Antiviral Activity and Safety with Atazanavir ± Ritonavir. 8th International AIDS Society (IAS) Conference on HIV Pathogenesis Treatment and Prevention; July 19-22, 2015; Vancouver, Canada. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2015. Available at: http://www.natap.org/2015/IAS/IAS_25.htm. Last accessed on September 23, 2016.
- U.S. Food and Drug Administration. Guidance for Industry: Role of HIV Resistance Testing in Antiretroviral Drug Development, October 2007. Page 19. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071173.pdf. Last accessed on September 23, 2016.
- Nowicka-Sans B, Protack T, Lin Z, et al. BMS-955176: Characterization of a Second-Generation HIV-1 Maturation Inhibitor. Poster presented at: 8th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 19-22, 2015; Vancouver, Canada. Poster TUPEA078. Available at: http://pag.ias2015.org/PAGMaterial/eposters/1723.pdf. Last accessed on September 23, 2016.
- Lin Z, Cantone J, Protack T, et al. Maturation Inhibitor Mechanistic Studies - Understanding and Modeling Differential Inhibition of Gag Polymorphs. Poster presented at: 22nd Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Poster 539. Available at: http://www.croiconference.org/sites/default/files/posters-2015/539.pdf. Last accessed on September 23, 2016.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on September 23, 2016.
- Bristol-Myers Squibb. Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and BMS-955176 With Atazanavir +/- Ritonavir (Open-Labeled) in HIV-1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2013. NLM Identifier: NCT01803074. Available at: https://clinicaltrials.gov/ct2/show/NCT01803074. Last accessed on September 23, 2016.
- Hwang C, Schürmann D, Sobotha C, et al. Second-generation HIV-1 Maturation Inhibitor BMS-955176: Overall Antiviral Activity and Safety Results from the Phase IIa Proof-of-Concept Study (AI468002). 15th European AIDS Conference (EACS); October 21-24, 2015; Barcelona, Spain. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2015. Available at: http://www.natap.org/2015/EACS/EACS_09.htm. Last accessed on September 23, 2016.
- Bristol-Myers Squibb. A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and Efficacy of BMS-955176 in Combination With Dolutegravir and Atazanavir (With or Without Ritonavir) in Treatment-Experienced HIV-1 Infected Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 6, 2015. NLM Identifier: NCT02386098. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02386098. Last accessed on September 23, 2016.
- Bristol-Myers Squibb. A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy, and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 11, 2015. NLM Identifier: NCT02415595. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02415595. Last accessed on September 23, 2016.
- Bristol-Myers Squibb: Press Release, dated October 23, 2015. Complete Phase 2a Study of HIV-1 Investigational Maturation Inhibitor Demonstrates Positive Results for Therapy Designed to Attack Virus Differently Than Existing Treatments. Available at: http://news.bms.com/press-release/complete-phase-2a-study-hiv-1-investigational-maturation-inhibitor-demonstrates-positi. Last accessed on September 23, 2016.
Last Reviewed: September 23, 2016