Fostemsavir for HIV

Overseen By Wendy Wert

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Orlando Immunology Center

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Immunomodulators

Disqualifiers: Recent HIV, HBV, HCV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding Fostemsavir to the treatment of HIV patients with stable virus levels but poor immune health can improve their immune system. Fostemsavir helps by blocking the virus from entering and destroying immune cells.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires you to continue your stable HIV treatment and add Fostemsavir to it.

What data supports the effectiveness of the drug Fostemsavir for treating HIV?

Fostemsavir has been shown to be effective for people with HIV-1 who have tried many other treatments without success. It works by blocking the virus from attaching to immune cells, and studies have shown it helps control the virus in patients with limited treatment options. ^{1 2 3 4 5}

Is fostemsavir safe for humans?

Fostemsavir is generally well-tolerated with relatively few drug interactions, as shown in clinical trials for HIV-1 treatment. It has been approved by the FDA and European Medicines Agency, indicating it meets safety standards for use in humans. ^{2 4 6 7 8}

How is the drug fostemsavir different from other HIV treatments?

Fostemsavir is unique because it is an attachment inhibitor that prevents HIV from attaching to and entering immune cells by binding to a specific part of the virus called gp120. This mechanism is different from other HIV treatments, which often target different stages of the virus's life cycle. ^{1 3 5 6 9}

Research Team

Charlotte-Paige M Rolle, MD, MPH

Principal Investigator

Orlando Immunology Center

Eligibility Criteria

This trial is for HIV-1 infected adults aged 18-65 with stable insurance, who have been on a consistent ARV regimen for over six months and have maintained low viral loads but poor CD4 T-cell count recovery. Participants must have had less than 350 cells/mm3 while on ARVs for at least two years and attended at least two clinic visits in the past year.

Inclusion Criteria

Documented plasma HIV-1 RNA < 50 c/mL x 2 within the last year prior to screening

My CD4+T-cell count is below 350, despite being on ARVs for 2+ years.

I am willing to add FTR 600 mg twice daily to my current HIV treatment.

Exclusion Criteria

My liver disease is not stable or I have severe liver disease.

Active HBV or HCV co-infection

History of autoimmune disease

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fostemsavir added to their stable HIV regimen to evaluate changes in immunologic parameters

48 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fostemsavir

Trial Overview The RECOVER study tests if adding Fostemsavir (Rukobia) to a stable HIV treatment helps improve immune system markers like CD4 T-cell counts in patients whose levels haven't risen sufficiently despite having their virus under control.

Participant Groups

Group I: FTR+suppressive regimen Experimental Treatment 1 Intervention

addition of fostemsavir 600 mg PO BID to the stable suppressive HIV regimen in immunologic non responders

Who Is Running the Clinical Trial?

Orlando Immunology Center

Lead Sponsor

Trials

6

Recruited

130+

ViiV Healthcare

Industry Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Findings from Research

Fostemsavir, an attachment inhibitor for HIV-1, was tested in a phase 2b trial with 251 treatment-experienced subjects, showing similar response rates to ritonavir-boosted atazanavir despite some subjects developing resistance to raltegravir.

While fostemsavir led to more frequent changes in viral susceptibility compared to atazanavir, some patients still achieved viral suppression below detectable levels, indicating potential efficacy even with emergent gp120 substitutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir. Lataillade, M., Zhou, N., Joshi, SR., et al.[2020]

Fostemsavir, the first oral attachment inhibitor for HIV-1, has shown clinical efficacy in heavily treatment-experienced adults, making it a promising option for those with multidrug-resistant HIV-1 infections.

The drug is generally well-tolerated, with common side effects including nausea and headache, and it can be taken with acid suppressive agents, but caution is needed when coadministering with strong CYP3A inducers to avoid reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir: The first oral attachment inhibitor for treatment of HIV-1 infection. Chahine, EB.[2021]

In a Phase 1 study with 14 healthy participants, co-administration of fostemsavir and maraviroc led to a 25% increase in maraviroc's plasma concentration over time, indicating a potential interaction, but without significant clinical implications.

The study concluded that fostemsavir and maraviroc can be safely co-administered without requiring dose adjustments, ensuring effective treatment for patients with multidrug-resistant HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug-drug interaction between the antiretroviral agents fostemsavir and maraviroc: a single-sequence crossover study in healthy participants. Wire, MB., Magee, M., Ackerman, P., et al.[2022]

Fostemsavir is the first FDA and EMA-approved attachment inhibitor for HIV-1, specifically designed for heavily-treatment-experienced individuals with multi-drug resistant HIV-1, highlighting its importance in expanding treatment options for this high-risk population.

The review discusses fostemsavir's mechanism of action, pharmacodynamics, pharmacokinetics, and its efficacy and safety, emphasizing its role in suppressing HIV-1 replication and improving the quality of life for patients who have failed previous antiretroviral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Profile of Fostemsavir for the Treatment of People with Human Immunodeficiency Virus-1 (HIV-1): Current Evidence and Place in Therapy. Muccini, C., Canetti, D., Castagna, A., et al.[2022]

In a phase 3 trial involving 371 patients with multidrug-resistant HIV-1, fostemsavir significantly reduced HIV-1 RNA levels compared to placebo, with a mean decrease of 0.79 log10 copies per milliliter versus 0.17 log10 copies (P<0.001) after 8 days.

At 48 weeks, 54% of patients in the randomized cohort achieved a virologic response (HIV-1 RNA <40 copies/mL), demonstrating sustained efficacy of fostemsavir, although 7% of patients discontinued due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. Kozal, M., Aberg, J., Pialoux, G., et al.[2020]

Fostemsavir, an attachment inhibitor for HIV-1, demonstrated a virological response rate of 61-82% in treatment-experienced patients after 48 weeks, comparable to 71% for the standard treatment (ritonavir-boosted atazanavir).

The treatment was generally well tolerated, with no adverse events leading to discontinuation, indicating its safety for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial. Thompson, M., Lalezari, JP., Kaplan, R., et al.[2018]

Fostemsavir is an FDA-approved HIV-1 attachment inhibitor that effectively prevents the virus from attaching to the CD4 receptor, making it a novel treatment option for patients with multidrug-resistant HIV-1.

Clinical trials show that fostemsavir is well tolerated and, when used with optimal background therapy, leads to virologic suppression in many heavily treatment-experienced individuals, highlighting its potential as a valuable addition to HIV treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir: a first-in-class HIV-1 attachment inhibitor. Grant, PM., Kozal, MJ.[2023]

Fostemsavir, a first-in-class HIV-1 attachment inhibitor, has been shown to be highly potent against most HIV-1 subtypes, with the majority of isolates exhibiting IC50 values below 10 nM, indicating strong efficacy in preventing HIV-1 infection.

The study analyzed 1337 HIV-1 isolates and found that temsavir's effectiveness is consistent across different tropisms (CCR5, CXCR4, and dual mixed-tropic), suggesting that its mechanism of action is broadly applicable regardless of the virus's entry pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay. Gartland, M., Zhou, N., Stewart, E., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Fostemsavir: The first oral attachment inhibitor for treatment of HIV-1 infection. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug-drug interaction between the antiretroviral agents fostemsavir and maraviroc: a single-sequence crossover study in healthy participants. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Profile of Fostemsavir for the Treatment of People with Human Immunodeficiency Virus-1 (HIV-1): Current Evidence and Place in Therapy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Fostemsavir: a first-in-class HIV-1 attachment inhibitor. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Fostemsavir for the treatment of HIV. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay. [2021]