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AIDSinfo Drug Database

AIDSinfo Drug Database

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FDA-approved

Investigational

Fostemsavir  Audio icon

Other Names: BMS-663068, Fostemsavir tromethamine, prodrug of BMS-626529, prodrug of temsavir
Drug Class: Entry and Fusion Inhibitors
Registry Number: 864953-29-7 (CAS)
Company: Bristol-Myers Squibb
Phase of Development: IIb
Chemical Image:
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fostemsavir
fostemsavir
Molecular Weight: 583.4954
(Compound details obtained from ChemIDplus Advanced1 and NIAID Therapeutics Database2)

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 safe and effective 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 IIb clinical trial.2,6

What have recent studies shown about fostemsavir?

In a Phase IIa study (known as AI438006), two different strengths of fostemsavir were studied in HIV-infected participants who had HIV-1 subtype B. Some of the participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had taken HIV medicines previously (also called treatment-experienced). The treatment-experienced participants were required to be off HIV medicines for at least 8 weeks before starting fostemsavir. Participants were assigned to one of the following five treatment groups for 8 days:

  • 600 mg of fostemsavir plus ritonavir (a protease inhibitor medicine; brand name: Norvir) 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.3,7,8

In this study, fostemsavir was shown to have substantial antiviral activity, decreasing viral load (the amount of HIV in a blood sample) from baseline. Investigators concluded that fostemsavir may be given either once or twice daily and with or without a ritonavir booster. (A booster drug is a second drug used to increase the effectiveness of the main [first] drug.) 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.3,7

In a Phase IIb study (known as AI438011), investigators looked at the safety and effectiveness of several fostemsavir dosages and compared them to the safety and effectiveness of the FDA-approved protease inhibitor atazanavir (brand name: Reyataz) boosted with ritonavir (brand name: Norvir). Participants were HIV-infected, treatment-experienced adults. All participants also 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.) 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 100 mg of ritonavir once daily plus a background regimen.6,9,10

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 alone without any other HIV medicines (also called monotherapy) for 7 days.9,10

In the main study, Week 24 results showed that fostemsavir had a similar effectiveness at reducing viral load across all fostemsavir groups and when compared to ritonavir-boosted atazanavir. In the sub-study, fostemsavir monotherapy reduced viral load after 7 days of treatment. In terms of safety, fostemsavir did not cause any serious side effects or side effects leading to study drop-outs.9,10

 

What side effects might fostemsavir cause?

In the Phase IIa study 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.7

In the Phase IIb study also discussed under the previous question, no safety concerns associated with fostemsavir treatment were identified.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.

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/864953-29-7. Last accessed on September 23, 2014.
  2. 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, 2014.
  3. 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 September 23, 2014.
  4. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/701213-36-7. Last accessed on September 23, 2014.
  5. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on September 23, 2014.
  6. 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 September 23, 2014.
  7. 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.
  8. 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 September 23, 2014.
  9. Lalezari J, Latiff GH, Brinson C, et al. Attachment Inhibitor Prodrug BMS-663068 in ARV-Experienced Subjects: Week 24 Analysis. Abstract presented at: 21st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6 2014; Boston, MA. Abstract 86. Available at: http://croi2014.org/sites/default/files/uploads/CROI2014_Final_Abstracts.pdf. Last accessed on September 23, 2014.
  10. Lalezari J, Latiff GH, Brinson C, et al. HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 24 Analysis. 21st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2014; Boston, MA. Levin: HIV-1 Attachment Inhibitor Prodrug in Antiretroviral-Experienced Subjects: Week 24 Analysis; Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/CROI/croi_26.htm. Last accessed on September 23, 2014.
 


Last Reviewed: September 23, 2014

Last Updated: September 23, 2014


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