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.
What is fostemsavir?
Fostemsavir (also known as BMS-663068) is an investigational drug that is being studied for the treatment of HIV infection.
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.3
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 (also known as BMS-626529).3,4
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.5
- 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.5
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.5
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: AI438006; NCT01009814
Participants: HIV-infected adults with subtype B virus. Some participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had previously taken HIV medicines (also called treatment-experienced). Treatment-experienced participants were required to be off HIV medicines for at least 8 weeks before starting fostemsavir.
Purpose: The purpose of this study was to evaluate the safety and antiviral activity of fostemsavir, given with and without a low dose of the medicine ritonavir (brand name: Norvir).
Study Design: This was an 8-day study of fostemsavir given orally. Fostemsavir was given alone without any other HIV medicines that had antiviral activity (also called monotherapy). (In this study, ritonavir was given at a low dose and acted only as a possible booster for fostemsavir. When ritonavir is used as a booster for an antiretroviral drug, ritonavir interferes with the breakdown of the other drug, which allows the other drug to remain in the body longer at a higher concentration.) Participants were assigned to one of the following five groups:
- 600 mg of fostemsavir plus ritonavir every 12 hours
- 1200 mg of fostemsavir plus ritonavir at bedtime
- 1200 mg of fostemsavir plus ritonavir every 12 hours
- 1200 mg of fostemsavir every 12 hours plus ritonavir every morning
- 1200 mg of fostemsavir every 12 hours
- In this 8-day study, fostemsavir given with or without a ritonavir booster proved effective at substantially reducing viral load (the amount of HIV in a blood sample) across all groups.
- Adding a ritonavir booster increased levels of fostemsavir in the body only a small amount and did not appear to increase the effectiveness of fostemsavir at reducing participants’ viral load. Investigators concluded that fostemsavir may be given either once or twice daily and with or without a ritonavir booster.
- In terms of safety, there were no “clinically relevant” effects on electrocardiogram (ECG), laboratory values, vital signs, or physical exams. The most common side effects were mild headache and rash.3,6,7
Study Names: AI438011; NCT01384734
Location: South America, North America, Europe, and Africa
Participants: HIV-infected, treatment-experienced adults
Purpose: The purpose of this study was to evaluate the safety and effectiveness of four different doses of fostemsavir and to compare fostemsavir to the FDA-approved protease inhibitor atazanavir (brand name: Reyataz) boosted with ritonavir.
Study Design: Participants were assigned to one of the following five dosing groups:
- 400 mg of fostemsavir twice daily plus a background regimen
- 800 mg of fostemsavir twice daily plus a background regimen
- 600 mg of fostemsavir once daily plus a background regimen
- 1200 mg of fostemsavir once daily plus a background regimen
- 300 mg of atazanavir boosted with ritonavir once daily plus a background regimen
All participants received a background regimen of the FDA-approved integrase inhibitor raltegravir (brand name: Isentress) and the FDA-approved nucleoside reverse transcriptase inhibitor tenofovir disoproxil fumarate (brand name: Viread). (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.)
A sub-study of fostemsavir was also performed prior to the main study described above. During the sub-study, a portion of participants from each fostemsavir dosing group took fostemsavir monotherapy for 7 days.
- In the sub-study, fostemsavir monotherapy proved capable of reducing participants’ viral load after 7 days of treatment.
- In the main study, after 24 weeks of treatment and continuing through 48 weeks of treatment, fostemsavir had a similar effectiveness at reducing viral load across all fostemsavir groups when compared to ritonavir-boosted atazanavir.
- In terms of safety, fostemsavir did not cause any serious side effects or side effects leading to study drop-outs.8-10
Study Names: AI438-047; NCT02362503
Location: North America, South America, Europe, Asia, Africa, and Australia
- HIV-infected, treatment-experienced adults who are experiencing treatment failure on their current antiretroviral therapy (ART) regimen. (Treatment failure is when an ART regimen is unable to control HIV infection.)
- Participants can no longer receive HIV medicines from at least three antiretroviral drug classes. (This may be because a participant’s HIV will not respond to certain HIV medicines, because of drug side effects that a patient cannot tolerate, or because of other reasons.)
- Participants have two 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 Design: Participants will be enrolled into one of two groups. The group assignment will be based on how many “fully active” FDA-approved HIV medicines a participant has remaining to form a new background regimen. (Fully active HIV medicines are ones that are expected to work successfully based on a participant’s treatment history, drug resistance test results, and/or the way a drug works against HIV.)
Group 1: Participants with at least one (but no more than two) fully active FDA-approved HIV medicines that can be used to form a new background regimen will be enrolled in this group.
- Once enrolled, participants will be randomly assigned to receive either 600 mg of fostemsavir twice daily or placebo twice daily for 8 days. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Participants will also continue to receive their current failing ART.
- Afterwards, starting on Day 9 through at least 48 weeks, all participants will receive 600 mg of fostemsavir twice daily plus a new optimized background regimen. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.)
Group 2: Participants without any fully active FDA-approved HIV medicines that can be used to form a new background regimen can be enrolled in this group.
- Participants in this group will receive 600 mg of fostemsavir twice daily plus an optimized background regimen for at least 48 weeks. (The optimized background regimen may contain the investigational entry inhibitor ibalizumab.)
* Study AI438-047 is currently recruiting participants, and results are not yet available.11-13
What side effects might fostemsavir cause?
In the Phase IIa study (Study AI438006) discussed under the previous question, which looked at treatment with different doses of fostemsavir over 8 days, the most common side effects were mild headache and rash.6
In the Phase IIb study (Study AI438011) also discussed under the previous question, no safety concerns associated with fostemsavir treatment were identified through 48 weeks of treatment.10
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.
I am interested in participating in a clinical trial of fostemsavir. 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.5
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 November 1, 2015.
- 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 November 1, 2015.
- 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 November 1, 2015.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/701213-36-7. Last accessed on November 1, 2015.
- 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 November 1, 2015.
- Nettles R, Schurmann D, Zhu L, et al. Pharmacodynamics, Safety, and Pharmacokinetics of BMS-663068: A Potentially First-in-class Oral HIV Attachment Inhibitor. Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); February 27-March 2, 2011; Boston, MA. Paper 49. Available at: http://retroconference.org/2011/Abstracts/41942.htm. Last accessed on May 29, 2013.
- 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 November 1, 2015.
- 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 November 1, 2015.
- 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 November 1, 2015.
- Thompson M, Lalezari J, Kaplan R, et al. Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 48 Analysis. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Poster 545. Available at: http://www.croiconference.org/sites/default/files/posters-2015/545.pdf. Last accessed on November 1, 2015.
- 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 November 1, 2015.
- Jain M. BMS AI438-047: 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. Clinical Trial Details from UT Southwestern Medical Center. Available at: http://www.utsouthwestern.edu/research/fact/detail.html?studyid=STU%20022015-035. Last accessed on November 1, 2015.
- Clayden P, Collins S, Frick M, et al. HIV i-BASE/Treatment Action Group. 2015 Pipeline Report. Benzacar A, ed. July 2015. Pages 11-12. Available at: http://www.treatmentactiongroup.org/sites/g/files/g450272/f/201509/2015%20Pipeline%20Report%20Full.pdf. Last accessed on November 1, 2015.
Last Reviewed: November 1, 2015