Drug Database: Panobinostat

What is panobinostat?What is panobinostat?

What is panobinostat?

Panobinostat is a drug that was previously approved by the U.S. Food and Drug Administration (FDA) under the brand name Farydak for the treatment of a certain type of cancer.⁵ Panobinostat is currently being studied as an investigational drug as part of a strategy to cure HIV infection. As an investigational HIV therapy, panobinostat 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.^6–8

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 panobinostat and other HIV-fighting strategies, including ongoing antiretroviral therapy (ART), may fully eliminate HIV from the body.^6-8 To learn more, see the HIVinfo What is a Latent HIV Reservoir? fact sheet.

Select clinical trials of panobinostatSelect clinical trials of panobinostat

Select clinical trials of panobinostat

Study Names: CLEAR; NCT01680094

Phase: 1/2
Status: This study has been completed.
Location: Denmark
Purpose: The purpose of this study was to evaluate the safety and effectiveness of panobinostat in reactivating latent HIV within resting CD4 cells.⁹
Selected Study Results: Results published in Lancet HIV (2014) showed that panobinostat administered to participants with viral suppression on ART was effective in reactivating latent HIV. However, panobinostat did not reduce the size of the latent HIV reservoir.¹⁰
Additional Published Material:

• IAS Towards an HIV Cure Symposium, 2013: Cyclic panobinostat (LBH589) dosing in HIV-1 patients: findings from the CLEAR trial
• CROI, 2015: Panobinostat broadly activates latent HIV-1 proviruses in patients

Study Names: ACTIVATE; NCT02471430

Phase: 1/2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate whether a combination of the HDAC inhibitor panobinostat and the immunomodulator peginterferon alfa-2a could reduce the latent HIV reservoir.¹¹
Selected Study Results: Results published in Cell (2024) and presented at CROI 2022 indicated that panobinostat and interferon alfa-2a reactivated latent HIV and induced immune activation in participants with viral suppression on ART. The combination regimen produced no major change in total HIV-1 proviral DNA, but a trend for a decrease of intact proviruses was seen. (Intact HIV-1 proviruses are proviruses which are capable of replicating and may contribute to viral rebound.)^12,13

Study Names: ORBIT; NCT06240520

Phase: 1/2
Status: See the ClinicalTrials.gov record for this study’s status.
Location: Netherlands
Purpose: The purpose of this study is to evaluate the ability of combination therapy with three latency-reversing agents — pyrimethamine, lenalidomide, and panobinostat — in reactivating latent HIV.¹⁴

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

What side effects might panobinostat cause?What side effects might panobinostat cause?

What side effects might panobinostat 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 panobinostat listed above.

CLEAR (NCT01680094) 

In this trial, all panobinostat-related side effects were mild in severity. The most common side effect related to panobinostat was fatigue. Some minor changes in white blood cell counts and platelet counts were seen, but these changes were temporary.¹⁰

ACTIVATE (NCT02471430)

In this trial, most of the side effects that occurred were mild to moderate in severity. The most common side effects with panobinostat were nausea and mild diarrhea. A case of temporary neutropenia was noted in one participant who received panobinostat plus peginterferon alfa-2a. There were no serious side effects reported.^11,12

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

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

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

More information about panobinostat-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 6918837, Panobinostat. Accessed June 10, 2024
2. Treatment Action Group website. Research toward a cure trials. Accessed June 10, 2024
3. pharmaand GmbH. Farydak 10mg hard capsules summary of product characteristics (SmPC), September 30, 2023. Electronic Medicines Compendium (EMC). Accessed June 10, 2024
4. Masetti R, Serravalle S, Biagi C, Pession A. The role of HDACs inhibitors in childhood and adolescence acute leukemias. J Biomed Biotechnol. Published online Article ID 148046 2011. doi:10.1155/2011/148046. Accessed June 10, 2024
5. Secura Bio, Inc.: Press Release, dated November 30, 2021. Secura Bio announces U.S. withdrawal of FARYDAK® (panobinostat) NDA. Accessed June 10, 2024
6. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096. Accessed June 10, 2024
7. 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 June 10, 2024
8. National Institute of Allergy and Infectious Diseases (NIAID). HIV viral eradication. Accessed June 10, 2024 
9. University of Aarhus. The safety and efficacy of the histone deacetylase inhibitor panobinostat for purging HIV-1 from the latent reservoir (CLEAR) study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 3, 2012. NLM Identifier: NCT01680094. Accessed June 10, 2024
10. Rasmussen TA, Tolstrup M, Brinkmann CR, et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a Phase 1/2, single group, clinical trial. Lancet HIV. 2014;1(1):e13-21. doi:10.1016/S2352-3018(14)70014-1. Accessed June 10, 2024
11. Massachusetts General Hospital. A Phase I-II pilot study to assess the safety and efficacy of combined administration with pegylated interferon-alpha2a and the histone deacetylase inhibitor (HDACi) panobinostat for reducing the residual reservoir of HIV-1 infected cells in cART-treated HIV-1 positive individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 11, 2015. NLM Identifier: NCT02471430. Accessed June 10, 2024
12. Armani-Tourret M, Gao C, Hartana CA, et al. Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a. Cell. 2024;187(5):1238-1254.e14. doi:10.1016/j.cell.2024.01.037. Accessed June 10, 2024
13. Armani-Tourret M, Hartana CA, Rassadkina Y, et al. HIV-1 viral reservoir disruption with panobinostat and IFN-⍺. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI)); February 12-16, 2022; Virtual. Poster 357. Accessed June 10, 2024
14. Erasmus Medical Center. Optimizing reversal of HIV latency with combination therapy (pyrimethamine, lenalidomide, panobinostat). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 26, 2024. NLM Identifier: NCT06240520. Accessed June 10, 2024