Drug Database: Romidepsin

What is romidepsin?What is romidepsin?

What is romidepsin?

Romidepsin is a drug that has been approved by the U.S. Food and Drug Administration (FDA) under the brand name Istodax for the treatment of a certain type of cancer.⁴ Romidepsin is also being studied as an investigational drug as part of a strategy to cure HIV infection. As an HIV investigational drug, romidepsin belongs to a group of drugs called latency-reversing agents.²

To learn about 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 do latency-reversing agents work?How do latency-reversing agents work?

How do latency-reversing agents work?

Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the latent HIV reservoir. Because HIV in this latent state is inactive, the immune system cannot detect the virus, and the antiretroviral (ARV) drugs that are used to treat HIV have no effect on it.^5–7

Latency-reversing agents work by drawing HIV out of its latent state within resting CD4 cells. Once the latent HIV is reactivated, the CD4 cells that harbor the virus are more likely to be recognized and killed by the body’s immune system or may be killed by certain HIV therapies, such as those that can enhance the body’s immune response to HIV. Researchers hope that the combined use of romidepsin and other HIV-fighting strategies, including ongoing antiretroviral therapy (ART), may fully eliminate HIV from the body.^5–7 To learn more, see the HIVinfo What is a Latent HIV Reservoir? fact sheet.

Select clinical trials of romidepsinSelect clinical trials of romidepsin

Select clinical trials of romidepsin

Study Names: REDUC; NCT02092116

Phase: 1b/2a
Status: This study has been completed.
Location: Denmark
Purpose: The REDUC trial was a two-part study. Part A was designed to find a safe and effective dose of romidepsin for latency reversal to use in the second part of the study. Part B was designed to evaluate the effect of the investigational therapeutic HIV vaccine Vacc-4x plus adjuvant combined with romidepsin on the latent HIV reservoir and viral load levels during an analytical treatment interruption of ART.⁸
Selected Study Results: Results from Part A of the trial published in PLoS Pathogens (2015) showed that romidepsin could safely reverse HIV latency. Part B results published in the Lancet HIV (2016) indicated that the combination of Vacc-4x plus adjuvant and romidepsin produced approximately a 40% reduction in the size of the latent HIV reservoir. The combined strategy, however, had no effect on prolonging the time from ART interruption to viral rebound.^9,10

Study Names: ACTG 5315; NCT01933594

Phase: 1/2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to look at the safety of single and multiple doses of romidepsin and to determine the effectiveness of these different doses in reactivating latent HIV within resting CD4 T cells.¹¹
Selected Study Results: Results published in The Journal of Infectious Diseases (2021) indicated that single and multiple romidepsin infusions were generally safe. No severe or worse side effects were reported in the single-dose study groups. One case of severe neutropenia (possibly related to romidepsin) was reported in the multidose study group. Both single and multiple romidepsin administration had no significant effect on reactivating latent HIV in participants with viral suppression on ART.¹²

Names: ROADMAP; NCT02850016

Phase: 2a
Status: This study has been completed.
Locations: Denmark, Germany, United States
Purpose: The purpose of this study was to compare the effectiveness of romidepsin plus the investigational bNAb 3BNC117 to the effectiveness of romidepsin administered alone in delaying or preventing viral rebound during an analytical treatment interruption of ART.^13,14
Selected Study Results: Results published in The Lancet Microbe (2022) showed that romidepsin plus 3BNC117 and romidepsin given alone had no substantial effect on reducing latent HIV reservoir size in participants with viral suppression on ART. Additionally, romidepsin plus 3BNC117, compared to romidepsin given alone, was not effective in delaying the time to viral rebound during analytical treatment interruption. The observed time to viral rebound was not clinically meaningful in either group.¹⁴ 

Study Names: BIOSKILL; EudraCT 2015-003186-28

Phase: 2
Status: This study has been completed.
Locations: Australia, Europe, United States
Purpose: The purpose of this study was to evaluate the safety and effectiveness of the combined use of Vacc-4x plus adjuvant when given prior to romidepsin. The researchers measured the effects of this combination strategy on viral load, latent HIV, and the body’s immune responses.¹⁵

Study Names: eCLEAR; NCT03041012

Phase: 1b/2a
Status: This study has been completed.
Locations: Denmark, United Kingdom
Purpose: The purpose of this study was to evaluate whether the early use of romidepsin and/or 3BNC117 in treatment-naive individuals who were initiating ART could reduce the time to viral suppression, limit latent HIV reservoir size, and delay the time to viral rebound during an analytical treatment interruption of ART.^2,16,17
Selected Study Results: Results presented at CROI 2022 and published in Nature Medicine (2022) showed that the early administration of 3BNC117, with or without romidepsin, led to faster viral load decline and significantly enhanced the elimination of infected cells after ART initiation, as compared to what was observed in participants receiving ART only. After 1 year, latent HIV reservoir size was reduced from baseline in all treatment groups, with the greatest reduction seen in people receiving 3BNC117 plus ART. Among participants who received 3BNC117 and had 3BNC117-sensitive virus, 80% maintained viral control during treatment interruption of ART. In contrast, among participants who had 3BNC117-resistant virus or did not receive 3BNC117, only 20% maintained viral control during treatment interruption.^17,18

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

Additional early-phase studies investigating romidepsin for HIV treatment have been or are being conducted, including:

• BCN02-Romi trial (NCT02616874): A Phase 1 study that enrolled participants from the BCN01 vaccine trial in which two therapeutic HIV vaccines (ChAdV63.HIVconsv and MVA.HIVconsv ) were evaluated. In the BCN02-Romi trial, participants were given booster vaccinations with MVA.HIVconsv in combination with romidepsin and underwent an analytical treatment interruption of ART. BCN02-Romi was completed, and results are available from Frontiers in Immunology (2020).^19,,20
• SYNACTHIV (NCT05230368): A Phase 1 trial evaluating the safety and tolerability of a combination of two HIV latency-reversing agents (decitabine and romidepsin) in men with subtype B HIV who have viral suppression on ART. This study is currently recruiting participants.²¹

What side effects might romidepsin cause?What side effects might romidepsin cause?

What side effects might romidepsin cause?

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

REDUC (NCT02092116)

In Part A of the REDUC trial, all romidepsin-related side effects were mild in severity and resolved within a few days. The most common side effects related to romidepsin were abdominal symptoms (such as nausea, stomach growling, and abdominal pain) and fatigue. Some mild changes in white blood cell counts and T cell counts were seen.⁹

In Part B of the REDUC trial, the majority of side effects were mild in severity. Side effects associated with romidepsin included fatigue and nausea. One side effect associated with romidepsin—mild hair loss—did not resolve by the end of the study. Side effects related to Vacc-4x plus the adjuvant and to the treatment interruption also occurred.¹⁰

ACTG 5315 (NCT01933594)

Participants who received single doses of romidepsin tolerated the drug well and had no severe treatment-related serious side effects. Seven participants who received romidepsin had side effects of moderate intensity that were possibly treatment-related, including fatigue, heart rhythm abnormality, low levels of phosphate in the blood, and neutropenia.¹²

Among 16 total participants enrolled to receive multiple-dose romidepsin or placebo, one participant experienced severe neutropenia that was possibly related to treatment. Four participants experienced one or more moderate side effects that were possibly, probably, or definitely related to romidepsin treatment; these included blurred vision, neutropenia, nausea, fatigue, and headache.¹²

ROADMAP (NCT02850016)

In the ROADMAP trial, most of the side effects reported during the study were mild or moderate. Out of 267 side effects that were reported during the trial, 39 were drug-related and 159 side effects were considered at least possibly related to romidepsin or 3BNC117. One participant had a serious side effect that was related to romidepsin treatment – higher than normal levels of bilirubin in the blood. (In this participant, bilirubin levels returned to normal without any treatment.) The most common side effects associated with romidepsin were nausea, headache, chills, and vomiting. Three participants experienced a temporary heart rhythm abnormality one day after receiving romidepsin.¹⁴

eCLEAR (NCT03041012)

In the Phase 1b/2a eCLEAR study looking at the use of romidepsin and/or 3BNC117 in participants initiating ART, the majority of side effects that occurred during the trial were mild or moderate and unrelated to study treatment. There were 85 side effects related to romidepsin treatment, with the most common being nausea and fatigue.¹⁷

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

Additional information on side effects known to be associated with romidepsin can be found in the FDA-approved Full Prescribing Information for Istodax.⁴

Where can I get more information about clinical trials studying romidepsin?Where can I get more information about clinical trials studying romidepsin?

Where can I get more information about clinical trials studying romidepsin?

More information about romidepsin-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.)

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.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem compound summary for CID 3425, romidepsin. Accessed April 5, 2024
2. Treatment Action Group. Research toward a cure trials. Accessed April 5, 2024
3. Masetti R, Serravalle S, Biagi C, Pession A. The role of HDACs inhibitors in childhood and adolescence acute leukemias. J Biomed Biotechnol. Published online 2011. doi:10.1155/2011/148046. Accessed April 5, 2024
4. Celgene Corporation. Istodax: full prescribing information, January 21 2023. DailyMed. Accessed April 5, 2024
5. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096. Accessed April 5, 2024
6. Rasmussen TA, Tolstrup M, Winckelmann A, Østergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccines Immunother. 2013;9(4):790-799. Accessed April 5, 2024
7. National Institute of Allergy and Infectious Diseases (NIAID). HIV viral eradication. Accessed April 5, 2024
8. Bionor Immuno AS. An open Phase I/IIa study to evaluate the safety and effect of therapeutic HIV-1 immunization using Vacc-4x + rhuGM-CSF, and HIV-1 reactivation using romidepsin, on the viral reservoir in virologically suppressed HIV-1 infected adults on cART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2014. NLM Identifier: NCT02092116. Accessed April 5, 2024
9. Søgaard OS, Graversen ME, Leth S, et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog. 2015;11(9). doi:10.1371/journal.ppat.1005142. Accessed April 5, 2024
10. Leth S, Schleimann MH, Nissen SK, et al. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016;3(10):e463-e472. doi:10.1016/S2352-3018(16)30055-8. Accessed April 5, 2024
11. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I/II study of romidepsin in HIV-infected adults with suppressed viremia on antiretroviral therapy to assess safety, tolerability, and activation of HIV-1 expression. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 28, 2013. NLM Identifier: NCT01933594. Accessed April 5, 2024
12. McMahon DK, Zheng L, Cyktor JC, et al. A Phase 1/2 randomized, placebo-controlled trial of romidespin in persons with HIV-1 on suppressive antiretroviral therapy. J Infect Dis. 2020;224(4):648-656. doi:10.1093/infdis/jiaa777. Accessed April 5, 2024
13. Rockefeller University. A Phase 2a, randomized study of romidepsin with or without 3BNC117 to evaluate the effects on the HIV-1 reservoir (ROADMAP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02850016. Accessed April 5, 2024
14. Gruell H, Gunst JD, Cohen YZ, et al. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. Lancet Microbe. 2022;3(3):e203-e214. doi:10.1016/S2666-5247(21)00239-1. Accessed April 5, 2024
15. EU Clinical Trials Register. EudraCT Number: 2015-003186-28; BIOSKILL: studying Vacc-4x, an HIV therapeutic vaccine, an assessment of immune-mediated anti-viral effects, when administered with adjuvant GM-CSF prior to HIV latent reservoir activation by the HDAC inhibitor, romidepsin. Accessed April 5, 2024
16. Aarhus University Hospital. Early administration of latency reversing therapy and broadly neutralizing antibodies to limit the establishment of the HIV-1 reservoir during initiation of antiretroviral treatment - a randomized controlled trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2017. NLM Identifier: NCT03041012. Accessed April 5, 2024
17. Gunst JD, Pahus MH, Rosás-Umbert M, et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022;28(11):2424-2435. doi:10.1038/s41591-022-02023-7. Accessed April 5, 2024
18. Gunst JD, Pahus MH, Rosás-Umbert M, et al. The impact of 3BNC117 and romidepsin treatment at ART initiation on HIV-1 persistence. International AIDS Society (IAS) Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2022. Accessed April 5, 2024
19. IrsiCaixa. An open label Phase I trial to evaluate the safety and effect of HIVconsv vaccines in combination with histone deacetylase inhibitor romidepsin on the viral rebound kinetic after treatment interruption in early treated HIV-1 infected individuals (BCN02-Romi). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered November 9, 2015. NLM Identifier: NCT02616874. Accessed April 5, 2024
20. Mothe B, Rosás-Umbert M, Coll P, et al. HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02). Front Immunol. 2020;11:823. doi:10.3389/fimmu.2020.00823. Accessed April 5, 2024
21. ANRS, Emerging Infectious Diseases. A pilot open label Phase I trial to evaluate the safety and the tolerability of a combination of two HIV-1 inducers in HIV+ sub-type B patients under cART with undetectable viral load. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 23, 2021. NLM Identifier: NCT05230368. Accessed April 5, 2024