What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is panobinostat?
Panobinostat (brand name: Farydak) is a drug that has been approved by FDA for the treatment of a certain type of cancer. It is currently being studied to see if it could be effective as part of a strategy to cure HIV infection.3,5,6
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 T cells) for many months or even years. While HIV is in this latent state, the immune system cannot recognize the virus, and antiretroviral therapy (ART) has no effect on it. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)7,8
Panobinostat belongs to a general class (group) of HIV drugs called latency-reversing agents.2 There are different types of latency-reversing agents. Panobinostat is a type of latency-reversing agent called a histone deacetylase (HDAC) inhibitor.9
How do latency-reversing agents work?
Latency-reversing agents reactivate (turn back on) latent HIV within resting CD4 T cells. When latent HIV is reactivated, it is once again able to produce new virus and multiply (replicate). It is hoped that after latent HIV is reactivated, the CD4 T cells in which the virus was hiding are more likely to die off on their own or be recognized and killed by the body’s immune system.8,9
In addition, any new virus that is produced during reactivation can then be prevented from infecting other cells with the use of ongoing ART.8,9 Recent research has shown that additional therapies, together with latency-reversing agents, may be needed to fully eliminate latent HIV from the body.9
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.10
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.10
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.10 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.)
In what phase of testing is panobinostat?
Panobinostat is being studied in a Phase I/II clinical trial.2,5
What are some studies on panobinostat?
Study Names: CLEAR trial; NCT01680094
Sponsor: University of Aarhus
- Participants were HIV-infected adults who had taken HIV medicines continuously for more than 2 years before the start of the study.
- Participants' viral load levels (the amount of HIV in a blood sample) had been below 50 copies/mL for at least 2 years before the start of the study.
- Participants’ CD4 cell counts had been greater than 500 cells/mm3 within 1 year of starting the study. (A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell—in a sample of blood and is an important indicator of immune function.)
The purpose of this study was to evaluate the safety and effectiveness of panobinostat in reactivating latent HIV within resting CD4 cells.6,11
Study Names: ACTIVATE trial; NCT02471430
Sponsor: Massachusetts General Hospital
Location: United States
- Participants are HIV-infected adults who have been receiving ART for at least 2 years and have been receiving the same ART regimen for at least 12 weeks before the start of the study.
- Participants have had viral load levels less than 50 copies/mL for at least 2 years before the start of the study.
- Participants have CD4 cell counts of 400 cells/mm3 or more.
The purpose of this study is to evaluate whether a combination of the HDAC inhibitor panobinostat and the immunomodulator
peginterferon alfa-2a (brand name: Pegasys) can reduce latent HIV reservoirs. (Immunomodulators are substances that help to activate, boost, or restore normal immune function.)5
*This study is currently recruiting participants.
For more details on the studies listed above, see the Health Professional version
What side effects might panobinostat cause?
In the CLEAR trial (NCT01680094) discussed under the previous question, all panobinostat-related side effects were considered 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 the changes were temporary.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?
More information about panobinostat-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
How can I find more information about participating in a clinical trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.10
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/404950-80-7. Last accessed on February 14, 2017.
- Treatment Action Group website. Research Toward a Cure Trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on February 14, 2017.
- Novartis Pharmaceuticals Corporation. FARYDAK – panobinostat lactate capsule: Full Prescribing Information, February 2015. DailyMed. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7774972a-eeaa-4b9a-9e56-3fc1b968e86a. Last accessed on February 14, 2017.
- Masetti R, Serravalle S, Biagi C, and Pession A. The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias. J Biomed Biotechnol. Vol 2011; Article ID 148046. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026992/pdf/JBB2011-148046.pdf. Last accessed on February 14, 2017.
- 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02471430. Last accessed on February 14, 2017.
- 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01680094. Last accessed on February 14, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID): Bulletin, dated June 16, 2009. NIAID Invites Applications to Conduct Basic Research on HIV Persistence: Studies Key to Search for a Cure. Available at:https://wayback.archive-it.org/7761/20160907080510/http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Last accessed on February 14, 2017.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on February 14, 2017.
- Rasmussen TA, Tolstrup M, Winckelmann A, Ostergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccin Immunother. 2013 Apr 1;9(4):790-799. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903897/. Last accessed on February 14, 2017.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on February 14, 2017.
- Tolstrup M. Cyclic Panobinostat (LBH589) dosing in HIV-1 patients: Findings from the CLEAR trial. Slides presented at: 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; June 30 – July 3, 2013; Kuala Lumpur, Malaysia. Available at: https://www.iasociety.org/Web/WebContent/File/HIV_Cure_Symposium_2013/Session%203_Martin%20Tolstrup.pdf. Last accessed on February 14, 2017.
- 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. Oct 2014; 1(1):e13-e21. DOI: 1.0.1016/S2352-3018(14)70014-1. Available at: https://www.researchgate.net/publication/280290228_Panobinostat_a_histone_deacetylase_inhibitor_for_latent_virus_reactivation_in_HIV-infected_patients_on_suppressive_antiretroviral_therapy_A_phase_12_single_group_clinical_trial. Last accessed on February 14, 2017.
Last Reviewed: February 15, 2017