What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (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 fostemsavir?
Fostemsavir (GSK3684934; formerly BMS-663068) is an investigational drug that is being studied for the treatment of HIV infection.4
Fostemsavir belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
By attaching to the gp120 protein on the outer surface of HIV, fostemsavir blocks HIV from getting into and infecting the immune cells.5
Fostemsavir is a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, fostemsavir is converted to temsavir (GSK2616713; formerly BMS-626529).4-6
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.7
- 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.7
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to 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.7 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different sublevels typically mean that a study is researching certain types of information or using a certain type of participant population.)
In what phase of testing is fostemsavir?
Fostemsavir is currently being studied in a Phase III clinical trial.2
What are some studies on fostemsavir?
Study Names: AI438-006; NCT01009814
Sponsor: Bristol-Myers Squibb
- Participants were HIV-infected adults with subtype B HIV.
- Some of the participants had never taken HIV medicines before or had taken an HIV medicine for less than 1 week. Other participants had previously taken HIV medicines for a longer period of time. All participants were required to be off HIV medicines for at least 8 weeks before starting fostemsavir.
- Participants had viral load levels of at least 5,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 counts of at least 200 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
Purpose: The purpose of this study was to evaluate the safety and effectiveness of fostemsavir, given with and without the medicine ritonavir (brand name: Norvir).5,8
Study Names: AI438-011; NCT01384734
Sponsor: Bristol-Myers Squibb
Location: Multiple countries, including United States
- Participants were HIV-infected adults who had taken HIV medicines before.
- Participants had less than 1 week of treatment with any HIV medicines from the integrase strand transfer inhibitors drug class.
- Participants had viral load levels of at least 1,000 copies/mL and CD4 counts greater than 50 cells/mm3 at the start of the study.
Purpose: The purpose of this study was to evaluate the safety and effectiveness of 4 different doses of fostemsavir and to compare fostemsavir to the FDA-approved protease inhibitor atazanavir (brand name: Reyataz) boosted with ritonavir.9,10
Study Names: AI438-047; NCT02362503
Sponsor: Bristol-Myers Squibb
Location: North America, South America, Europe, Asia, Africa, and Australia
- Participants are HIV-infected, treatment-experienced adults.
- Participants are experiencing treatment failure on their current antiretroviral therapy (ART) regimen, with viral load levels of at least 400 copies/mL. (Treatment failure is when an ART regimen is unable to control HIV infection.)
- Participants can no longer receive HIV medicines from at least 3 antiretroviral drug classes. (This may be because a participant’s HIV is not affected by certain HIV medicines, because of drug side effects that a participant cannot tolerate, or because of other reasons.)
- Participants have 2 or fewer antiretroviral drug classes remaining to form a new ART regimen.
Purpose: The purpose of this study is to evaluate the safety and effectiveness of fostemsavir.
* Study AI438-047 is currently recruiting participants, and results are not yet available.11
What side effects might fostemsavir cause?
In the Phase IIa study (Study AI438-006; NCT01009814) discussed under the previous question, the most common side effects were headache, rash, and urinary urgency. Most instances of these 3 side effects were mild.5,8
In the Phase IIb study (Study AI438-011; NCT01384734), mild headache was the most common side effect. Through 96 weeks of treatment, there were no cases of fostemsavir-related side effects that led to participants stopping the study.4,9,12
Because fostemsavir is still being studied, information on possible side effects of the drug is not complete. As testing of fostemsavir continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying fostemsavir?
More information about fostemsavir-related research studies is available from the AIDSinfo database of ClinicalTrials.gov 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.7
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/864953-29-7. Last accessed on December 2, 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 December 2, 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 December 2, 2016.
- Llamoso C, Bogner JR, Afonina L, et al. HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 96 Safety Analysis. International Congress of Drug Therapy in HIV Infection (HIV Glasgow); October 23-26, 2016; Glasgow, UK. Levin: HIV-1 Attachment Inhibitor Prodrug BMS-663068 [GSK3684934 (formerly BMS-663068)] in Antiretroviral-Experienced Subjects: Week 96 Safety Analysis; Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. Available at: http://natap.org/2016/GLASGOW/GLASGOW_32.htm. Last accessed on December 2, 2016.
- Nettles RE, Schürmann D, Zhu L, et al. Pharmacodynamics, Safety, and Pharmacokinetics of BMS-663068, an Oral HIV-1 Attachment Inhibitor in HIV-1-Infected Subjects. J Infect Dis. 2012 Oct 1;206(7):1002-11. Available at: http://jid.oxfordjournals.org/content/206/7/1002.long. Last accessed on December 2, 2016.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/701213-36-7. Last accessed on December 2, 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 December 2, 2016.
- Bristol-Myers Squibb. Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 6, 2009. NLM Identifier: NCT01009814. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01009814. Last accessed on December 2, 2016.
- Bristol-Myers Squibb. A Phase IIb Randomized, Controlled, Partially-Blinded Trial to Investigate Safety, Efficacy and Dose-Response of BMS-663068 in Treatment-experienced HIV-1 Subjects, Followed by an Open-Label Period on the Recommended Dose. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 23, 2011. NLM Identifier: NCT01384734. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01384734. Last accessed on December 2, 2016.
- Lalezari JP, Latiff GH, Brinson C, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomized controlled trial. Lancet HIV. 2015; 2: e427-e437. National AIDS Treatment Advocacy Project (NATAP): HIV Articles. Available at: http://www.natap.org/2015/HIV/2PIIS2352301815001770(1).pdf. Last accessed on December 2, 2016.
- Bristol-Myers Squibb. A Multi-arm Phase 3 Randomized Placebo Controlled Double Blind Clinical Trial to Investigate the Efficacy and Safety of BMS-663068 in Heavily Treatment Experienced Subjects Infected With Multi-drug Resistant HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 9, 2015. NLM Identifier: NCT02362503. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02362503. Last accessed on December 2, 2016.
- DeJesus E, Martins M, Stoehr A, et al. Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 96 Analysis. Poster presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Poster 472. Available at: http://www.croiconference.org/sites/default/files/posters-2016/472.pdf. Last accessed on December 2, 2016.
Last Reviewed: December 2, 2016