Drug Database: Lexgenleucel-T

What is lexgenleucel-T?

Lexgenleucel-T is an investigational gene therapy product that is being studied to treat or possibly cure HIV.^2-4 Gene therapy is a technique that is used to modify genes in order to treat or prevent disease.

To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How does lexgenleucel-T work?

Lexgenleucel-T is an investigational gene therapy product that adds an anti-HIV gene (called an antisense gene) into CD4 cells.⁵

With lexgenleucel-T, the antisense gene is delivered into the CD4 cell by a carrier called a vector. The antisense gene becomes a permanent part of the cell’s genetic material. Then, when HIV infects a CD4 cell that has the antisense gene and tries to make copies of itself, the antisense gene is activated. The activated antisense gene prevents the production of an HIV protein (called an envelope protein) that’s needed for HIV to successfully replicate. Without the envelope protein, HIV cannot multiply.^5-7

Select clinical trials of lexgenleucel-T

Study Names: Protocol 802456; NCT00295477
Phase: 1/2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety and effectiveness of multiple lexgenleucel-T Infusions on viral load levels and CD4 counts.⁸
Selected Study Results: Results published in the journal Blood (2013) showed that infusions of lexgenleucel-T were associated with decreases in viral load set points after an analytical treatment interruption of ART. After lexgenleucel-T infusions, CD4 counts increased; however, during ART treatment interruption, participants’ CD4 counts decreased significantly from baseline compared to participants who did not undergo treatment interruption. The infusions of lexgenleucel-T were found to be safe with no treatment-related serious side effects.⁹
Additional Published Material:

• CROI, 2010: Prolonged control of viremia after transfer of autologous CD4 T cells genetically modified with a lentiviral vector expressing long antisense to HIV env (VRX496)

Study Names: (1) VRX496-USA-05-002; NCT00131560 and (2) VRX496-USA-05-002-Rollover; NCT00622232
Phase: 2
Status: These studies are ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of the VRX496-USA-05-002 study is to evaluate the safety and effectiveness of single and multiple infusions of lexgenleucel-T. The purpose of the rollover study is to evaluate the safety and effectiveness of an additional infusion of lexgenleucel-T in participants who complete the VRX496-USA-05-002 study.^3,4
Selected Study Results: Results published in Molecular Therapy (2010) (abstract 646) showed that single and multiple lexgenleucel-T infusions did not significantly reduce participants’ viral load levels at the one year post-infusion time point. In most participants, lexgenleucel-T had no consistent effect on CD4 counts; however, a single dose of lexgenleucel-T was found to significantly increase CD4 counts in a small number of participants. The infusions of lexgenleucel-T were found to be safe with no serious side effects identified during the study.¹⁰
Additional Published Material:

• IAS, 2011: Autologous T-cell therapy based on a lentiviral vector expressing long antisense RNA targeted against HIV-1 env gene influences HIV replication and evolution in vivo
• Mol Ther, 2010 (abstract 803): Long term persistence of VRX496-modified CD4+ T lymphocytes following lexgenleucel-T infusions for the treatment of HIV/AIDS: results from a Phase 2 clinical trial

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might lexgenleucel-T cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in the studies of lexgenleucel-T listed above.

No safety concerns related to multiple infusions were reported in this study. The most common side effect was a garlic/creamed corn odor occurring during infusions. Other common side effects related to treatment were reactions at the infusion site, such as stinging and a cold sensation.^9,11

Twenty-seven participants in these studies have completed 3 years of follow-up safety monitoring with no evidence of long-term safety issues related to lexgenleucel-T treatment.¹⁰

Because lexgenleucel-T is still being studied, information on possible side effects of the drug is not complete. As testing of lexgenleucel-T continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying lexgenleucel-T?

More information about lexgenleucel-T-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests. To learn more about the ClinicalTrials.gov search features, please see How to Search.)

Some clinical trials may be looking for volunteer participants. 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: Lexgenleucel-T. https://chem.nlm.nih.gov/chemidplus/rn/1294006-17-9. Accessed August 16, 2022     
2. Treatment Action Group website. Research toward a cure trials. https://www.treatmentactiongroup.org/cure/trials/. Accessed August 16, 2022     
3. VIRxSYS Corporation. A Phase II, open-label, multicenter study to evaluate the safety, tolerability, and biological activity of single and repeated doses of autologous T cells transduced with VRX496 in HIV-positive subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 16, 2005. NLM Identifier: NCT00131560. https://clinicaltrials.gov/ct2/show/NCT00131560. Accessed August 16, 2022     
4. VIRxSYS Corporation. A rollover study to evaluate safety and therapeutic effect of re-infusing subjects who completed participation in the VRX496-USA-05-002 trial with autologous T cells transduced with VRX496. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 11, 2008. NLM Identifier: NCT00622232. https://clinicaltrials.gov/ct2/show/NCT00622232. Accessed August 16, 2022   
5. VIRxSYS Corporation. FDA biological response modifiers advisory committee meeting briefing package—Autologous T cells transduced with VRX496, an HIV-1 based lentiviral vector for the treatment of patient-subjects infected with HIV-1; October 26th, 2001. https://web.archive.org/web/20180127035407/https://www.fda.gov/ohrms/dockets/ac/01/briefing/3794b3_13_sponsor.pdf. Accessed August 16, 2022 
6. Sheehy J, Zack J, Kiem HP, Handibode J. Cell/gene therapy—HIV cure research training curriculum. Located on the AVAC website (http://www.avac.org/cure-curriculum/module3) under PowerPoint. https://www.avac.org/sites/default/files/u16/Gene_Cell_Therapy_July.pptx. Accessed August 16, 2022    
7. Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19.
8. University of Pennsylvania. A Phase I/II, open-label, single center study to evaluate the tolerability, trafficking and therapeutic effects of repeated doses of autologous T cells transduced with VRX496 in HIV infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 21, 2006. NLM Identifier: NCT00295477. https://clinicaltrials.gov/ct2/show/NCT00295477. Accessed August 16, 2022     
9. Tebas P, Stein D, Binder-Scholl G, et al. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV. Blood. 2013;121(9):1524-1533. doi:10.1182/blood-2012-07-447250
10. Rebello T, Stein D, Blick G, et al. Safety and efficacy of autologous CD4+ T cells transduced with a lentiviral vector delivering anti-HIV RNA antisense env in HIV+ subjects failing one or more HAART regimens. Mol Ther. 2010;18:S251-S252. doi:10.1016/S1525-0016(16)38087-X
11. Tebas P, Stein D, Zifchak L, et al. Prolonged control of viremia after transfer of autologous CD4 T cells genetically modified with a lentiviral vector expressing long antisense to HIV env (VRX496). 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2010. http://www.natap.org/2010/CROI/croi_182.htm. Accessed August 16, 2022