NOTE: The development of MPC-4326 for HIV treatment has been discontinued.
The study of MPC-4326 as a maturation inhibitor HIV medicine was discontinued in 2010. The company developing the drug announced that this decision was made for strategic business reasons and that the company was focusing its resources on cancer drug development.3 Two journal articles noted that, in Phase II clinical trials, MPC-4326 was found to be ineffective in some participants with HIV that had specific naturally occurring polymorphisms. (Polymorphisms are naturally occurring genetic variations [mutations] in HIV that are not caused by antiretroviral drug use.)4,5
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.
What is MPC-4326?
MPC-4326 is an investigational drug that has been studied for the treatment of HIV infection.
MPC-4326 belongs to a class (group) of HIV drugs called maturation inhibitors.4 Maturation inhibitors prevent the processing of a long HIV protein chain called Gag. The processing of Gag is necessary to form mature and infectious HIV (HIV that is capable of infecting other cells in the body).
Maturation inhibitors work by binding to a specific location on the Gag protein chain. This binding prevents protease, an HIV enzyme, from breaking Gag into specific, smaller protein units needed to create mature and infectious virus. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) When mature and infectious virus cannot be formed, this prevents HIV from multiplying and can reduce the amount of HIV in the body.4,6,7
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.8
- 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.8
In most cases, an investigational drug must be proven safe and effective 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.8
In what phase of testing is MPC-4326?
MPC-4326 has been studied in Phase II clinical trials.2 The development of MPC-4326 for the treatment of HIV infection was discontinued in 2010.3-5
What are some studies on MPC-4326?
Study Name: Study 204
Participants: HIV-infected adults who either had never taken HIV medicines before entering the study (treatment-naive) or had taken HIV medicines previously (treatment-experienced).
Purpose: The main purpose of this study was to look at the safety and effectiveness of two different strengths of MPC-4326 given without any other HIV medicines (also called monotherapy) over 14 days. After 14 days, researchers planned to continue evaluating MPC-4326 for up to 72 weeks, but this time the drug would be given with an optimized background regimen. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.)
Study Design: Participants were randomly assigned to take either 200 mg or 300 mg of MPC-4326 twice daily. During the first 14 days of the study, MPC-4326 was given as monotherapy. After 14 days, participants who showed a certain level of viral load decline (viral load is the amount of HIV in the blood) had the option to continue taking MPC-4326 along with an optimized background regimen. No control arm was used in this study.
- Both doses of MPC-4326 monotherapy reached “target” concentration levels in the body. (Target concentration levels were the levels needed to lower viral load).
- The average lowering of viral load in the 200-mg group and the 300-mg group was not significantly different.
- Using data from two previous Phase II studies, researchers developed a model to predict who would respond well to treatment with MPC-4326 and who would not. The model was based on whether or not someone’s HIV had certain polymorphisms. In the two studies, the model was able to correctly predict 80% of people who responded well to treatment and 89% of people who did not respond well to treatment.
- Researchers used the model described in the bullet above to identify which participants would respond well to MPC-4326 treatment in Study 204. Participants that had been predicted to respond well to treatment (those without a polymorphic form of HIV) had a greater decrease in viral load than participants that were predicted not to respond well to MPC-4326 treatment (those who had a polymorphic form of HIV).
- Among participants that were predicted to respond well to MPC-4326 treatment, MPC-4326 at the higher dose was more effective in lowering viral load than the lower dose of MPC-4326.
- In terms of safety, no study discontinuations or serious side effects occurred. One participant had severe constipation. The most common side effects were headache, diarrhea, and nausea.
- After completion of the 14-day monotherapy portion of the study, six participants continued MPC-4326 along with an optimized background regimen. At 48 weeks, four participants continued treatment with MPC-4326 and were able to maintain an undetectable viral load. (Undetectable viral load is when the amount of HIV in the blood is too low to be detected with a viral load test.)9-13
A Phase IIb study looking at the safety and effectiveness of MPC-4326 combined with an optimized background regimen was terminated prior to completion. Participants in this study were treatment-experienced individuals whose HIV wasn’t being controlled by their current antiretroviral therapy.14
What side effects might MPC-4326 cause?
In Study 204 discussed under the previous question, the most common side effects that occurred after 14 days of treatment with MPC-4326 were headache, diarrhea, and nausea.10,11
Information on possible side effects of the drug is not complete. If testing of MPC-4326 begins again, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying MPC-4326?
More information about MPC-4326-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.
I am interested in participating in a clinical trial of MPC-4326. 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.8
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/174022-42-5. Last accessed on April 29, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on April 29, 2015.
- Myrexis, Inc.: Press Release, dated June 8, 2010. Myriad Pharmaceuticals Announces Intent to Focus on Oncology Portfolio. Available at: http://www.myrexis.com/files/documents/Press%20Releases/2010/2010.06.08%20-%20Myriad%20Pharmaceuticals%20Announces%20Intent%20to%20Focus%20on%20Oncology%20Portfolio.pdf. Last accessed on April 29, 2015.
- Adamson CS. Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process. Mol Biol Int. 2012;2012:604261. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410323/. Last accessed on April 29, 2015.
- Waki K, Durell SR, Soheilian F, Nagashima K, Butler SL, Freed EO. Structural and Functional Insights into the HIV-1 Maturation Inhibitor Binding Pocket. PLoS Pathog. 2012 Nov;8(11):e1002997. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493477/. Last accessed on April 29, 2015.
- Sundquist WI, Kräusslich HG. HIV-1 Assembly, Budding, and Maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385941/. Last accessed on April 29, 2015.
- Brown KC, Paul S, Kashuba AD. Drug Interactions with New and Investigational Antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857544/. Last accessed on April 29, 2015.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on April 29, 2015.
- Myrexis Inc. A Phase II Multicenter, Open-label, Randomized, Parallel Group, Study of Bevirimat in HIV-1 Positive Patients to Evaluate the Safety, Efficacy, and Pharmacokinetics of MPC-4326 Administered as Monotherapy for 14 Days and as Part of an Optimized Background Regimen for up to 72 Weeks. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 25, 2009. NLM Identifier: NCT00967187. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00967187. Last accessed on April 29, 2015.
- Bloch M, Bodsworth N, Fidler M, et al. Efficacy, Safety and Pharmacokinetics of MPC-4326 (Bevirimat Dimeglumine) 200mg bid and 300mg bid Monotherapy Administered for 14 days in Subjects with HIV-1 Infection. Abstract presented at: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, CA. Abstract H-1230. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=30cfb0e3-06f8-42ba-b4fb-47507d251418&cKey=fc21de4f-4479-4a63-8db7-a7015967dcf3&mKey=14ebfe7e-6f65-4d97-8cb6-f64f4347c38a. Last accessed on April 29, 2015.
- Bloch M, Bodsworth N, Mather G, et al. Efficacy, Safety and Pharmacokinetics of MPC-4326 (bevirimat dimeglumine) 200mg BID and 300mg BID Monotherapy Administered for 14 days in Subjects with HIV-1 Infection. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, CA. Levin: Bevirimat Antiviral Activity & Safety, 14-Day Monotherapy Study; Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2009. Available at: http://www.natap.org/2009/ICCAC/ICCAC_43.htm. Last accessed on April 29, 2015.
- Myrexis, Inc.: Press Release, dated September 14, 2009. Myriad Pharmaceutical's Tablet Formulation of MPC-4326 Reduces Viral Load in HIV-1 Patients. Available at: http://www.myrexis.com/files/documents/Press%20Releases/2009/2009.09.14%20-%20Myriad%20Pharmaceuticals'%20Tablet%20Formulation%20of%20MPC-4326%20Reduces%20Viral%20Load%20in%20HIV-1%20Patients.pdf. Last accessed on April 29, 2015.
- Myriad Pharmaceuticals, Inc. Form 10-K (Annual Report), filed September 28, 2009. Available at: http://www.myrexis.com/files/documents/SEC%20Filings/Annual/2009.09.28%20-%2010-K%20Annual%20Report/10-K%20Annual%20Report%20Sep%2028,%202009.pdf. Last accessed on April 29, 2015.
- Myrexis Inc. A Phase 2b Multicenter, Randomized, Open Label, Comparative Trial of MPC-4326 in Combination With a Two to Three Drug Optimized Background Regimen Versus an Optimized, Three to Four Drug Antiretroviral Regimen for the Treatment of Triple Class Antiretroviral Experienced, HIV-1 Infected Subjects Failing Current Therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 2, 2009. NLM Identifier: NCT01026727. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01026727. Last accessed on April 29, 2015.
Last Reviewed: April 29, 2015