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.
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.5
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.5,6,7
MPC-4326 was the first maturation inhibitor to enter clinical development.5
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.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
MPC-4326 has been studied in Phase II clinical trials.2
Because MPC-4326 did not work well in certain participants who had a polymorphic (mutated) form of HIV, the clinical development of the drug was discontinued in 2010. (Polymorphisms are naturally occurring genetic variations [mutations] that are not caused by antiretroviral drug use.)5,9
A Phase II study (known as Study 204) compared the efficacy of two different strengths of MPC-4326, taken orally twice a day, in HIV-infected adults who either had never taken HIV medicines before entering the study (treatment-naive) or had taken HIV medicines previously (treatment-experienced). During the first 14 days, participants received MPC-4326 as monotherapy. (Monotherapy is the use of only one drug to treat an infection or disease and is not recommended for the treatment of HIV outside of a clinical trial.)10,11
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. (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.) No control arm was used in this study.10,11
In Study 204, both doses of MPC-4326 monotherapy reached targeted concentration levels in the body (levels that are predetermined in a laboratory setting and considered enough to stop virus replication by 90%). In terms of viral load reduction, participants with a polymorphic form of HIV appeared to have less of a response to 14 days of MPC-4326 treatment than participants with a wild-type (non-mutated) form of HIV. Among participants with wild-type HIV, MPC-4326 at the higher dose was more effective in reducing viral load than the lower dose.11 During this study, researchers also tested a method designed to predict which participants would respond to MPC-4326 treatment based on whether or not they had a polymorphic form of HIV. Eighty percent of participants were correctly predicted to respond to treatment, whereas 89% were correctly predicted to have no response to treatment. These results suggest that certain HIV polymorphisms (mutations) may be important factors in viral load decline.12 In terms of safety, no study discontinuations or serious or severe side effects occurred. The most common side effects were headache, diarrhea, and nausea.11
In Study 204, the most common side effects that occurred after 14 days of treatment with MPC-4326 were headache, diarrhea, and nausea.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.
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.
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.
1. United States National Library of Medicine. ChemIDplus Advanced. Last accessed on February 24, 2014.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on February 24, 2014.
3. National AIDS Treatment Advocacy Project (NATAP): HIV Articles. Maturation Inhibitor Bevirimat, now called MPC-4326, Starting Phase 2b in 2nd Half 2009. Last accessed on February 24, 2014.
4. Myrexis, Inc.: Press Releases, dated June 30, 2010. Myriad Pharmaceuticals Formally Adopts Its Name Change to Myrexis, Inc. Effective July 1, 2010. GlobeNewswire: Newsroom; 2010. Last accessed on February 28, 2014.
5. Adamson CS. Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process. Mol Biol Int. 2012;2012:604261. Last accessed on February 24, 2014.
6. Sundquist WI, Kräusslich HG. HIV-1 Assembly, Budding, and Maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. Last accessed on February 24, 2014.
7. Brown KC, Paul S, Kashuba AD. Drug Interactions with New and Investigational Antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. Last accessed on February 24, 2014.
8. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on February 24, 2014.
9. 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;8(11):e1002997. Last accessed on February 24, 2014.
10. 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. Last accessed on February 24, 2014.
11. 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. Last accessed on February 24, 2014.
12. 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: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2009. Last accessed on February 24, 2014.
Last Reviewed: February 28, 2014
Last Updated: February 28, 2014