Mycophenolate Mofetil
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Mycophenolate Mofetil
- Mycophenolate Mofetil: From Transplant Rejection Prophylaxis to HIV Infectious Disease
Mycophenolate Mofetil: From Transplant Rejection Prophylaxis to HIV Infectious Disease
One-Sentence Summary
Mycophenolate mofetil (MMF) is an IMPDH-inhibiting immunosuppressant marketed in the US in several forms. It is generally used to prevent organ rejection, although the supplied US labeling data does not state its indication. The TxGNN model predicts it may be effective for HIV infectious disease, with 9 clinical trials and 20 publications retrieved. Only a handful of these directly test MMF in HIV, and the evidence is early-stage and small-scale.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied US licensing data (MMF is generally used for organ-transplant rejection prophylaxis) |
| Predicted New Indication | HIV infectious disease |
| TxGNN Prediction Score | 99.86% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the DrugBank field. The evidence pack does supply a mechanistic rationale. The active form, mycophenolic acid, inhibits inosine monophosphate dehydrogenase (IMPDH). This depletes guanosine nucleotide pools and suppresses lymphocyte proliferation.
This links to HIV in two ways:
- Lower intracellular dGTP may potentiate guanosine-analogue antiretrovirals such as abacavir. Early clinical reports describe dGTP depletion and a fall in plasma HIV-1 RNA when MMF was added to abacavir-containing regimens.
- Suppressing activated CD4+ T-cell proliferation may limit chronic immune activation and infected-cell reservoirs.
The rationale is biologically plausible but has not been confirmed by a Phase 3 efficacy trial. Suppressing immunity in people with HIV is also a safety concern in its own right. The trial and literature records include several transplant-in-HIV studies where MMF is only part of the anti-rejection regimen. These are not tests of MMF as an HIV treatment.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00120419 | Phase 4 | Unknown | 90 | MAN2: MMF in antiretroviral-naive HIV-1 patients, testing effects on immune hyperactivation, CD4 decline and plasma HIV-1 RNA. No results provided. |
| NCT00247494 | Phase 4 | Unknown | 90 | MAN2 substudy of MMF effects on cardiovascular surrogate markers in HIV-1 infection. A secondary outcome, not antiviral efficacy. |
| NCT00038272 | Phase 1/2 | Completed | 56 | Randomized, placebo-controlled: DAPD vs DAPD plus MMF added to anti-HIV regimens in treatment-experienced patients. The automated relevance grade was low, but the summary shows MMF as a study arm. |
| NCT00021489 | Phase 1/2 | Withdrawn | 0 | MMF plus abacavir in treatment-failure HIV. Directly relevant, but never enrolled, so it provides no evidence. |
| NCT01453192 | Phase 3 | Completed | 27 | Kidney transplantation in HIV-1 patients on a raltegravir-based regimen. Its link to MMF as an HIV treatment cannot be established from the data. |
| NCT00009009 | Phase 2 | Completed | 10 | Kidney transplantation in HIV-infected patients. MMF is probably part of the immunosuppressive regimen, so this is transplant management. |
| NCT00112593 | N/A | Completed | 5 | Stem-cell transplant in HIV-positive patients using cyclosporine plus MMF. MMF is used for graft-versus-host disease prophylaxis. |
| NCT02793544 | Phase 2 | Completed | 80 | HLA-mismatched marrow transplant with post-transplant cyclophosphamide, sirolimus and MMF. HIV is at most incidental. |
Two further retrieved trials (NCT06869265, NCT01288131) are unrelated to HIV and are omitted.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12352149 | 2002 | Clinical study | J Acquir Immune Defic Syndr | MMF 500 mg twice daily added to abacavir-containing regimens in 5 patients failing therapy. Associated with intracellular dGTP depletion and a decrease in plasma HIV-1 RNA. |
| 11391161 | 2001 | Pilot study | J Acquir Immune Defic Syndr | Open-label pilot in 7 patients with multidrug-resistant HIV/AIDS (MMF, abacavir, didanosine, amprenavir, ritonavir). Well tolerated despite advanced disease. |
| 15353978 | 2004 | Clinical study | AIDS | HAART with or without MMF in treatment-naive patients, assessing plasma HIV-1 RNA decay and the latent cellular reservoir. |
| 15213566 | 2004 | Randomized pilot | J Acquir Immune Defic Syndr | 17 patients with early chronic HIV. MMF during and after HAART interruption, assessing immune response and viral load. |
| 16379601 | 2005 | Clinical study | AIDS Res Hum Retroviruses | No detrimental immunological effects of MMF plus HAART in treatment-naive acute and chronic HIV-1 patients. |
| 15871638 | 2005 | Pharmacokinetic study | Clin Pharmacokinet | PK/PD of low-dose MMF with abacavir, efavirenz and nelfinavir. Drug monitoring is recommended because of the low doses. |
| 15355127 | 2004 | Pharmacokinetic study | Clin Pharmacokinet | Effect of MMF on antiretroviral pharmacokinetics and on intracellular dCTP/dGTP pools. |
| 17885292 | 2007 | Clinical study | AIDS | Safety, tolerability and antiretroviral activity of DAPD (amdoxovir) with or without MMF in drug-resistant HIV. |
| 17017956 | 2006 | Review | Curr Top Med Chem | Immunosuppressive drugs in HIV disease, arguing that chronic immune activation is a therapeutic target alongside HAART. |
| 16515490 | 2006 | Review | Curr Pharm Des | Virostatics as a strategy against HIV, addressing gaps in current antiretroviral therapy. |
No randomized phase 3 publication was identified. The evidence is pilot-scale clinical studies, pharmacokinetic work and reviews, most from 2001 to 2007.
US Market Information
Approved-indication text was not provided for these entries.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA214871 | Mycophenolate Mofetil | Powder, for suspension | Amneal Pharmaceuticals NY LLC |
| NDA216482 | MYHIBBIN | Suspension | Azurity Pharmaceuticals, Inc. |
| ANDA065416 | mycophenolate mofetil | Tablet | Accord Healthcare Inc. |
| ANDA203859 | Mycophenolate Mofetil | Injection, powder, lyophilized, for solution | Mylan Institutional LLC |
| ANDA217031 | Mycophenolic Acid | Tablet, delayed release | Biocon Pharma Inc. |
Across all 20 authorizations, the available forms also include capsules and film-coated tablets. Oral, injectable and suspension routes are all available.
Safety Considerations
Please refer to the package insert for safety information.
- Repurposing-specific concern: Immunosuppression in HIV-infected patients is itself a safety risk. A 2006 mouse study (PMID 16621037) found that IMPDH inhibitors, including mycophenolic acid, enhanced SARS-CoV infectivity, which may signal a broader infection-related concern.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale is plausible, and small pilot studies from the early 2000s reported dGTP depletion and viral-load reductions with abacavir-based regimens. However, no completed Phase 2/3 efficacy trial with results supports MMF in HIV. The most relevant registered trials are withdrawn or of unknown status, and MMF’s immunosuppressive effect is a safety concern in this population. The pack’s blocking data gap on package-insert warnings also prevents safety screening.
To proceed, the following is needed:
- FDA package-insert warnings and contraindications (blocking gap).
- Detailed mechanism-of-action data from DrugBank.
- Results or status updates for the MAN2 trials (NCT00120419, NCT00247494), and clarification of the DAPD plus MMF trial (NCT00038272) outcomes.
- A risk-benefit assessment of immunosuppression in HIV-infected patients, including opportunistic-infection risk.
- Manual review of the trial relevance grades, since several were assigned from truncated titles.
Among the other predictions, multiple sclerosis has more supporting data (L2, several early-phase trials and a Cochrane review). It may be a better candidate to pursue first.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.