Drugs

INCB-9471

INCB-9471

Other Names: INCB 9471, INCB-009471, INCB-9471 dihydrochloride Drug Class: Entry Inhibitor Molecular Formula: C30 H40 F3 N5 O2 Registry Number: 925701-76-4 (CAS) Chemical Name: (4,6-dimethylpyrimidin-5-yl)-[4-[(3S,4R)-4-[(2R)-2-ethoxy-5-(trifluoromethyl)indan-1-yl]-3-methyl-piperazin-1-yl]-4-methyl-1-piperidyl]methanone Organization: Incyte Corporation Phase of Development: II (discontinued)

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and Treatment Action Group 2008 Pipeline Report3)

NOTE: The development of INCB-9471 for HIV treatment has been discontinued.

NOTE: The development of INCB-9471 for HIV treatment has been discontinued.

The study of INCB-9471 as an HIV medicine was discontinued. In 2008, the company developing INCB-9471, Incyte Corporation, announced that it would no longer study INCB-9471 and would instead seek a partner company to develop the drug. Incyte Corporation said that stopping INCB-9471 development would allow the company to focus its resources on programs with the “greatest near-term value.”3,4

What is an investigational drug?

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 INCB-9471?

What is INCB-9471?

INCB-9471 is an investigational drug that was studied for the treatment of HIV infection.

INCB-9471 belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.

INCB-9471 works by attaching to a protein on the surface of the immune cells. The protein is called the CCR5 co-receptor. When INCB-9471 attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.4

Research may prove that INCB-9471 is a safe and effective option for treating people with R5-tropic virus, including those for whom other entry and fusion inhibitors, such as maraviroc (brand name: Selzentry), are not working.5

How are clinical trials of investigational drugs conducted?

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.6

  • 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.6

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.6 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different sub-levels 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 INCB-9471?

In what phase of testing is INCB-9471?

INCB-9471 was last studied in Phase II clinical trials.2 The study of INCB-9471 as an HIV medicine has been discontinued. In 2008, the company developing INCB-9471, Incyte Corporation, announced that it was no longer studying INCB-9471 and was seeking a partner company to develop the drug. Incyte Corporation said that stopping INCB-9471 development would allow the company to focus its resources on programs with the “greatest near-term value.”3,4

What are some studies on INCB-9471?

What are some studies on INCB-9471?

Study Names: Not available
Organization: Incyte Corporation
Phase: IIa
Location: Not available
Participants:

  • Participants were HIV-infected adults who had R5-tropic virus.
  • Some of the participants had never taken HIV medicines before starting the study. Others had taken HIV medicines previously but had been off HIV medicines for at least 3 months before starting the study.
  • Participants had viral load levels greater than 10,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
  • Participants had CD4 counts greater than 500 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)

Purpose: The purpose of this study was to look at the safety, effectiveness, and drug properties of INCB-9471. INCB-9471 was given without any other medicines (also called monotherapy) and was compared to a placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)7,8

Study Names:INCB 9471-201; NCT00393120
Sponsor: Incyte Corporation
Phase: II
Location: United States
Participants

  • Participants were HIV-infected adults who had R5-tropic virus.
  • Some of the participants had never taken HIV medicines before starting the study. Others had taken HIV medicines previously but had been off HIV medicines for at least 3 months before starting the study.
  • Participants had viral load levels greater than 10,000 copies/mL and CD4 counts greater than 350 cells/mm3.

Purpose: The purpose of this study was to look at the safety, effectiveness, and drug properties of INCB-9471. INCB-9471 was given as monotherapy and was compared to a placebo.9

For more details on the studies listed above, see the Health Professional version.

What side effects might INCB-9471 cause?

What side effects might INCB-9471 cause?

In the first study discussed under the previous question, which was a 14-day Phase IIa study of INCB-9471 in HIV-infected adults, INCB-9471 was generally considered safe. Mild side effects reported during the study that may have been related to INCB-9471 treatment included constipation, diarrhea, nausea, headache, hiccups, and rash.7,8 

In previous studies of INCB-9471 in healthy study participants, some common side effects were headache, diarrhea, sore throat, and cold symptoms.10,11

If testing of INCB-9471 continues, additional information on possible side effects will be gathered.

 

Where can I get more information about clinical trials studying INCB-9471?

Where can I get more information about clinical trials studying INCB-9471?

More information about INCB-9471-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?

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.6

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

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/925701-76-4. Last accessed on January 24, 2017.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 24, 2017.
  3. Chou L, Harrington M, Huff B, et al. Treatment Action Group. 2008 Pipeline Report. July 2008. Available at: http://www.treatmentactiongroup.org/sites/default/files/2008%20pipeline_0.pdf. Last accessed on January 24, 2017.
  4. Incyte Corporation: Press Release, dated March 17, 2008. Incyte to Provide Update on Clinical Programs at Cowen Health Care Conference. Available at: http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=1119174&highlight. Last accessed on January 24, 2017.
  5. Shin N, Solomon K, Zhou N, et al. Identification and Characterization of INCB9471, an Allosteric Noncompetitive Small-Molecule Antagonist of C-C Chemokine Receptor 5 with Potent Inhibitory Activity against Monocyte Migration and HIV-1 iInfection. J Pharmacol Exp Ther. 2011 Jul; 338(1):228-39. Available at: http://jpet.aspetjournals.org/content/338/1/228.long. Last accessed on January 24, 2017.
  6. 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 January 24, 2017.
  7. Incyte Corporation: Press Release, dated July 24, 2007. Phase IIa Study Results Demonstrate that Once-Daily 200 mg Dosing of INCB9471 Provided Potent and Prolonged Antiviral Activity in HIV-Infected Patients. Accessed April 24, 2013. Available at: http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=1029620&highlight=. Last accessed on January 24, 2017.
  8. Cohen C, DeJesus E, Mills A, et al. Potent Antiretroviral Activity of the Once-Daily CCR5 Antagonist INCB009471 Over 14 Days of Monotherapy. 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Levin: New Incyte CCR5 Drug Shows Good Activity: 14 day monotherapy study; Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2007. Available at: http://www.natap.org/2007/IAS/IAS_19.htm. Last accessed on January 24, 2017.
  9. Incyte Corporation. A Randomized, Double-blind, Placebo-controlled Study Exploring the Safety, Tolerability, PK & Virological Effect of Once Daily Oral Dosing of INCB009471 as Monotherapy for 14 Days in ARV-naïve/Limited ARV-experienced, HIV-1 Infected Pts. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2006. NLM Identifier: NCT00393120. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00393120. Last accessed on January 24, 2017.
  10. Troy S, Emm T, Yeleswaram S, et al. Single and Multiple Dose Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor. Poster presented at: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2007; Chicago, IL. Poster H-1034. Available from Incyte Corporation at: http://library.corporate-ir.net/library/69/697/69764/items/261807/Poster%20H-1034.pdf. Last accessed on January 24, 2017.
  11. Troy S, Emm T, Yeleswaram S, et al. Effect of Ritonavir on the Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor. Poster presented at: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2007; Chicago, IL. Poster H-1035. Available from Incyte Corporation at: http://library.corporate-ir.net/library/69/697/69764/items/261808/Poster%20H-1035.pdf. Last accessed on January 24, 2017.

Last Reviewed: January 24, 2017