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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding the drug Fostemsavir to a stable HIV treatment plan can improve immune system markers in people with HIV who haven't seen their CD4 T-cells (cells that help fight infections) recover well. It targets individuals whose HIV is well-controlled but who still have low CD4 T-cell counts. Participants should have been on a stable HIV treatment for at least six months and be willing to add Fostemsavir to their regimen. This study may suit those with stable HIV who have not seen their immune system fully recover. As a Phase 4 trial, Fostemsavir is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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 is the safety track record for Fostemsavir?

Research has shown that fostemsavir is generally well-tolerated by patients. Long-term studies, including one that tracked patients for about five years, consistently found fostemsavir to be safe, with no new safety issues emerging over time. Another study, which examined data for nearly five years, also confirmed its tolerability.

However, one study indicated a higher risk of serious side effects with fostemsavir compared to other treatments at the 48-week mark. Despite this, the FDA has approved the treatment for another use, indicating a known safety profile. Overall, fostemsavir is considered generally safe for long-term use, though, like any medication, it may have side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Fostemsavir is unique because it targets HIV in a way that current treatments don't. While most HIV drugs focus on inhibiting viral enzymes like reverse transcriptase or protease, fostemsavir blocks the virus from attaching to human cells by binding to the gp120 protein on the virus's surface. This new mechanism of action offers hope for patients who have limited options due to resistance or intolerance to other drugs. Researchers are excited about fostemsavir because it can be added to existing regimens, potentially boosting their effectiveness for those who haven't responded well to other treatments.

What is the effectiveness track record for Fostemsavir in treating HIV?

Research has shown that fostemsavir, the investigational treatment in this trial, effectively treats HIV-1, particularly in individuals with drug-resistant strains. Studies found that it lowers virus levels in the blood, with 144 out of 272 patients showing a positive response. Additionally, patients treated with fostemsavir experienced significant increases in CD4 counts, crucial for a healthy immune system. Over approximately five years, those using fostemsavir-based treatments have continued to see these positive results. This medication, which prevents the virus from entering cells, has received approval from major health authorities for its effectiveness and safety in managing HIV-1 infection. ^{1 4 6 7 8}

Who Is on the Research Team?

Charlotte-Paige M Rolle, MD, MPH

Principal Investigator

Orlando Immunology Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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 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, 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8183480/

Long-term efficacy and safety of fostemsavir among ... In the Randomized Cohort, treatment with fostemsavir plus OBT resulted in a virologic response (HIV-1 RNA <40 copies/ml by Snapshot analysis) in 144 out of 272 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8800563/

Efficacy and Safety Profile of Fostemsavir for the Treatment ... Fostemsavir is the first attachment inhibitor approved by Food and Drug Administration and European Medicines Agency for the treatment of HIV-1 infection.

3. viivhealthcare.com viivhealthcare.com/en-us/media-center/news/press-releases/2022/july/viiv-healthcare-presents-positive-five-year-data-at-aids/

ViiV Healthcare presents positive five-year data at AIDS ... People living with multidrug-resistant HIV-1 treated for approximately five years with fostemsavir-based regimens experienced durable virologic responses.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902493

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection In patients with multidrug-resistant HIV-1 infection with limited therapy options, those who received fostemsavir had a significantly greater decrease in the ...

5. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30240-X/abstract

Safety and efficacy of the HIV-1 attachment inhibitor ... Response rates in the non-randomised cohort were 37% (37 of 99) at week 24 and week 96. Mean increases in CD4 counts from baseline at week 96 were 205 cells per ...

6. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1394644/full

Long-term safety and impact of immune recovery in heavily ... Analysis of long-term data over a median follow-up of 258 weeks in BRIGHTE shows that fostemsavir was well tolerated with a safety profile that was consistent ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0149291822001461

Comparative Efficacy and Safety of Fostemsavir in Heavily ... Safety Outcomes​​ Compared with OBT from VIKING-3, the odds of experiencing any SAE were higher with fostemsavir and OBT than with OBT alone at the week 48 data ...

8. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30240-X/fulltext

week 96 results of the phase 3 BRIGHTE study Fostemsavir in combination with an optimised background therapy was well tolerated with no new safety signals, and resulted in continued improvements in both ...