LefitolimodOther Names: MGN1703, dSLIM-30L1, double-stem-loop immunomodulator 30L1 Drug Class: Latency-Reversing Agents Registry Number: 1548439-51-5 (CAS) Chemical Class: Oligonucleotides Organization: Mologen AG Phase of Development: Lefitolimod is in Phase Ib/IIa development as an HIV therapeutic.
(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 NCI Drug Dictionary,3 and Mologen AG website4)
What is an investigational drug?
Anis one that is under study and is not approved by the U.S. (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 What is an Investigational HIV Drug? fact sheet.
What is lefitolimod?
Lefitolimod is an investigational drug that is being studied as part of a strategy to cure HIV.
Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that thecan remain hidden and inactive (latent) inside certain cells of the (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the . While HIV is in this latent state, the immune system cannot recognize the virus, and (ART) has no effect on it. (ART is the recommended treatment for HIV infection and involves using a combination of different [ARV] drugs to prevent HIV from replicating.)5,6
Lefitolimod belongs to a general class (group) of HIV drugs called latency-reversing agents. There are different types of latency-reversing agents. Lefitolimod is a type of latency-reversing agent called a toll-likeagonist.2
How do latency-reversing agents work?
Latency-reversing agents reactivate (turn back on) latent HIV within resting CD4 cells. When latent HIV is reactivated, it is once again able to produce new virus and multiply (). It is hoped that after latent HIV is reactivated, the CD4 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.6,7
In addition, any new virus that is produced during reactivation can then be prevented from infecting other cells with the use of ongoing ART.6,7 Recent research has shown that additional therapies, together with latency-reversing agents, may be needed to fully eliminate latent HIV from the body.7
Beyond its potential as a possible HIV latency-reversing agent, lefitolimod may also improve the body’sto HIV.8
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.9
- 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.9
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase IIIto 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.9
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 lefitolimod?
Lefitolimod is currently being studied in a Phase Ib/IIa clinical trial as a treatment for HIV.2
What are some studies on lefitolimod?
Study Names: TEACH study; NCT02443935
Sponsor: University of Aarhus
Status: This study has been completed.
- Participants were adults with HIV who had been on ART for at least 12 months.
- Participants had levels of no more than 50 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 counts greater than 350 cells/mm3 at the start of the study. (A is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
For more details on this study, see the Health Professional version.
What side effects might lefitolimod cause?
One goal of HIV research is to identify new drugs that have fewer side effects. In the TEACH study (NCT02443935) discussed under the previous question, the most commonly reported side effect was mild redness ( ) around the injection site, which resolved on its own. 8,10,11
Information on possible side effects of lefitolimod is not complete. As testing of lefitolimod continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying lefitolimod?
More information about lefitolimod-related research studies is available from the AIDSinfo database of 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.9
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: https://chem.nlm.nih.gov/chemidplus/rn/1548439-51-5. Last accessed on March 21, 2018.
- Treatment Action Group website. Research toward a cure trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on March 21, 2018. [Archived at WebCite]
- National Cancer Institute (NCI). NCI Drug Dictionary: TLR9 agonist MGN1703. Available at: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=686500. Last accessed on March 21, 2018. [Archived at WebCite]
- Mologen AG website. The product pipeline. Available at: http://www.mologen.com/en/products/product-pipeline.html. Last accessed on March 21, 2018. [Archived at WebCite]
- 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/6721/20160908184013/http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Last accessed on March 21, 2018.
- Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on March 21, 2018.
- 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: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903897/. Last accessed on March 21, 2018.
- University of Aarhus. Toll-like receptor 9 enhancement of antiviral immunity in chronic HIV-1 infection: a Phase 1b/2a trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 30, 2015. NLM Identifier: NCT02443935. Available at: https://clinicaltrials.gov/ct2/show/NCT02443935. Last accessed on March 21, 2018.
- National Institutes of Health (NIH). NIH clinical research trials and you. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on March 21, 2018.
- Vibholm, L, Schleimann, MH, Højen, JF, et al. Short-course Toll-like receptor 9 agonist treatment impacts innate immunity and plasma viremia in individuals with human immunodeficiency virus infection. Clin Infect Dis. 2017 June;64:1686-1695. Available at: http://www.natap.org/2017/HIV/cix201(1).pdf. Last accessed on March 21, 2018. [Archived at WebCite]
- Vibholm LK, Frattari G, Schleimann MH, et al. Effect of 24 weeks TLR9 agonist therapy on CTL responses and viral rebound during ATI. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI): March 4-7, 2018; Boston, MA. Poster 357. Available at: http://www.croiconference.org/sites/default/files/posters-2018/1430_Vibholm_357.pdf. Last accessed on March 21, 2018. [Archived at WebCite]
Last Reviewed: March 21, 2018