MedPath

FN-1501

Generic Name
FN-1501
Brand Names
Cellcept, Myfenax, CellCept, Mycophenolate mofetil Teva, Myclausen
Drug Type
Small Molecule
Chemical Formula
C22H25N9O
CAS Number
1429515-59-2
Unique Ingredient Identifier
6MC966B505
Background

Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). This drug is an immunosuppressant combined with drugs such as Cyclosporine and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants. It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995. In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis.

Previously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity. The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.

Indication

Mycophenolate mofetil is indicated in combination with other immunosuppressants to prevent the rejection of kidney, heart, or liver transplants in adult and pediatric patients ≥3 months old. Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy. Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.

Associated Conditions
Transplanted Organ Rejection

Belimumab Shows Superior Efficacy for Systemic Lupus Erythematosus in Meta-Analysis

• A comprehensive meta-analysis of five randomized controlled trials confirms belimumab's superior efficacy over placebo in treating systemic lupus erythematosus (SLE) according to BICLA criteria. • Patients receiving belimumab demonstrated significantly higher response rates regardless of baseline glucocorticoid dose, with particularly strong results in those with high disease activity or serologically active disease. • The findings validate belimumab's clinical efficacy through an additional widely used responder index, supporting its use in SLE management according to current recommendations.

Lupus Nephritis Market Expected to Grow as Novel Therapies Enter Clinical Trials

• The global lupus nephritis market is projected to grow significantly by 2034, with the United States accounting for over 80% of the current $1.12 billion market share across major regions. • Several innovative therapies are advancing through clinical trials, including CAR-T cell treatments from companies like Allogene Therapeutics, Adicet Bio, and Caribou Biosciences, which received FDA Fast Track designations. • Key pharmaceutical players including Aurinia Pharmaceuticals, AstraZeneca, and Roche are developing treatments such as voclosporin, anifrolumab, and obinutuzumab to address the significant unmet needs in lupus nephritis management.

UPLIZNA Becomes First FDA-Approved Treatment for IgG4-Related Disease, Reducing Flare Risk by 87%

• The FDA has approved UPLIZNA (inebilizumab-cdon) as the first and only treatment for adults with IgG4-related disease, a chronic immune-mediated inflammatory condition that can cause permanent organ damage. • In the pivotal MITIGATE trial, UPLIZNA demonstrated an 87% reduction in flare risk compared to placebo and allowed nearly 60% of patients to achieve corticosteroid-free, flare-free complete remission. • The approval marks Amgen's expanding leadership in CD19-directed B-cell depletion therapies across multiple autoimmune diseases, including NMOSD, IgG4-RD, and potentially generalized myasthenia gravis.

FDA Approval of Axatilimab Marks New Era in Chronic GVHD Treatment

• Axatilimab, a CSF1R-blocking antibody, received FDA approval in August 2024 for chronic graft-versus-host disease treatment, demonstrating a 74% overall response rate in clinical trials. • Novel therapies including baricitinib, ixazomib, and teduglutide show promising results in treating steroid-refractory GVHD, offering new hope for patients resistant to conventional treatments. • Pharmacists play a crucial role in GVHD management through medication monitoring, patient education, and therapeutic drug optimization, contributing to improved patient outcomes.

Gazyva Shows Significant Improvement in Lupus Nephritis Treatment: Phase III REGENCY Trial Results

• Genentech's Phase III REGENCY trial demonstrates that Gazyva plus standard therapy achieved 46.4% complete renal response in lupus nephritis patients compared to 33.1% with standard therapy alone. • The study, published in NEJM, showed clinically meaningful improvements in complement levels and reductions in anti-dsDNA markers, indicating reduced disease activity and inflammation. • Results were consistent across all patient subgroups, including those with Class IV lupus nephritis and higher baseline proteinuria levels, while maintaining Gazyva's established safety profile.

IASO Bio's CAR-T Therapy, Equecabtagene Autoleucel, Advances in Hong Kong and Singapore for Multiple Myeloma

• IASO Bio's Equecabtagene Autoleucel (FUCASO) NDA has been accepted by the Hong Kong Department of Health for relapsed/refractory multiple myeloma. • The CAR-T therapy, already approved in China, is the first fully human CAR-T product and has shown remarkable efficacy and safety. • Singapore Health Sciences Authority (HSA) has also accepted the NDA for Equecabtagene Autoleucel, marking a key step in IASO Bio's global expansion. • IASO Bio plans to implement a 'Manufactured in China, supplied overseas' model upon approval, expanding access to CAR-T therapies.

Belimumab Shows Superior Outcomes in Pediatric Lupus Nephritis Treatment Study

• A retrospective study at Children's Hospital of Fudan University demonstrates that belimumab combined with standard therapy achieved 97.1% renal response rate in childhood lupus nephritis, compared to 80% with standard therapy alone. • Children receiving belimumab showed faster treatment response within 3 months and maintained better outcomes through 24 months, with significantly higher sustained response rates. • The belimumab group achieved superior steroid reduction, with 82.9% of patients reaching glucocorticoid doses below 7.5mg daily at 12 months, compared to 30.4% in the standard therapy group.

Eledon's Tegoprubart Shows Promise in Functional Cure for Type 1 Diabetes

Eledon Pharmaceuticals reports a breakthrough in type 1 diabetes treatment, with two patients achieving insulin independence after receiving islet cell transplants combined with its experimental drug, tegoprubart. This pilot study, part of a broader effort to find safer immunosuppressant alternatives, marks a significant step towards functional cures for the disease.

Fate Therapeutics Shifts Focus to Autoimmune Diseases with Promising Cell Therapies

• Fate Therapeutics is expanding its focus to autoimmune diseases, leveraging its cell therapy platform with programs like FT819 and FT522. • Clinical progress includes dosing the first SLE patient in a Phase I study with FT819, with preliminary data expected later this year. • The company's strong financial position, with a cash runway extended to the end of 2026, supports ongoing research and development activities. • Upcoming data readouts from FT819 in SLE and FT522 in B-cell malignancies are expected to be critical catalysts for the company.

Novel Drug Regimens Show Promise in Reducing Graft-versus-Host Disease After Stem Cell Transplants

• A novel drug regimen (SIR/CSP/PTCy) significantly reduced moderate to severe chronic graft-versus-host disease (cGVHD) to 1% compared to 28% with the SIR/CSP/MMF regimen. • The SIR/CSP/PTCy regimen also improved one-year cGVHD-free relapse-free survival, showing 76% compared to 55% in the control group. • A Phase I trial of itacitinib showed promising results in preventing severe graft-versus-host disease (GvHD) in half-matched stem cell transplants, with no grade 3 or 4 GvHD observed. • Itacitinib, a JAK inhibitor, is being investigated for its potential to prevent GvHD when administered before stem cell transplantation, representing a new approach to managing this complication.

Gene-Edited Pig Kidney Functions in Macaque for Over Six Months in Chinese Study

• Chinese scientists achieved a breakthrough by maintaining a gene-edited pig kidney's function in a macaque for 184 days, marking progress in xenotransplantation. • The pig kidney, modified with four gene edits, functioned normally for five months in the macaque before chronic rejection began. • Researchers used an improved immunosuppressive regimen to extend graft survival, aiming to pave the way for human clinical trials. • This milestone brings China closer to international standards in xenotransplantation research, addressing the critical need for organ donors.

hUC-MSCs Show Promise in Treating Steroid-Refractory Acute Graft-versus-Host Disease

• A recent study investigates the efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in treating steroid-refractory acute graft-versus-host disease (SR-aGVHD). • The trial, involving 7 Chinese centers, randomized patients to receive either hUC-MSCs or a placebo, alongside a second-line treatment for SR-aGVHD. • Results indicated a higher overall response rate at day 28 in the hUC-MSC group compared to the control, suggesting potential therapeutic benefits. • The study highlights hUC-MSCs as a promising option for patients with SR-aGVHD, warranting further investigation in larger clinical trials.

EMA's CHMP Recommends Multiple New Medicines and расширения Indications in November and December 2024 Meetings

• The CHMP recommended eight medicines for approval in November, including Augtyro for advanced solid tumors and Lazcluze for first-line treatment of advanced non-small cell lung cancer. • Seventeen new medicines were recommended for approval in December, bringing the total for 2024 to 114, including Andembry for hereditary angioedema and Beyonttra for transthyretin amyloidosis. • Extensions of therapeutic indication were recommended for 11 medicines in November and 8 in December, expanding the use of already authorized treatments like Keytruda and Ofev. • The CHMP also reviewed and updated recommendations for several medicines, including Leqembi for Alzheimer's disease and Mysimba for weight loss, and addressed the withdrawal of Alofisel for Crohn's disease.

Tacrolimus Shows Superiority in Preventing Severe Acute GVHD After Haploidentical Stem Cell Transplant

• A recent study found that tacrolimus is more effective than cyclosporine A in preventing severe acute graft-versus-host disease (GVHD) in haploidentical hematopoietic cell transplantation. • The research, involving 2427 patients with acute myeloid leukemia, showed no significant differences in overall survival or relapse rates between the two drugs. • Tacrolimus was associated with a lower incidence of severe grade 3-4 acute GVHD compared to cyclosporine A in haploidentical transplants, but not in unrelated donor transplants. • The findings suggest tacrolimus may be the preferred option with mycophenolate mofetil for AML patients in first complete remission undergoing haploidentical HCT.

Eledon's Tegoprubart Shows Promise in Type 1 Diabetes Islet Transplantation

• Eledon Pharmaceuticals' tegoprubart, as part of an immunosuppression regimen, enabled insulin independence in two of three type 1 diabetes subjects after islet transplantation. • Islet engraftment was three to five times higher in subjects treated with tegoprubart compared to those receiving standard tacrolimus-based immunosuppression. • The treatment with tegoprubart was generally well-tolerated, with no unexpected adverse events or hypoglycemic episodes reported in the study. • These findings suggest tegoprubart's potential to improve islet transplant outcomes and reduce reliance on tacrolimus, offering a safer alternative for T1D patients.

Eledon's Tegoprubart Shows Promise in Type 1 Diabetes Islet Transplantation

• Eledon Pharmaceuticals reports that tegoprubart, combined with an immunosuppression regimen, enabled insulin independence in two of three T1D subjects post-islet transplant. • Islet engraftment was three to five times higher in subjects treated with tegoprubart compared to those receiving standard tacrolimus-based immunosuppression. • The treatment with tegoprubart was generally well tolerated, with no unexpected adverse events or hypoglycemic episodes reported during the study. • Data from the UChicago Medicine investigator-initiated trial were presented at the 5th IPITA/HSCI/Breakthrough T1D Stem Cells Summit.

ASN Kidney Week 2024: Novel Clinical Trials Highlight Advances in Kidney Disease Treatment

• Finerenone shows similar long-term kidney function patterns to placebo in heart failure patients, while reducing protein leakage, suggesting potential benefits in specific outcomes. • Remote diagnostic and therapeutic recommendations for acute kidney injury (AKI) improved clinician behaviors but did not significantly reduce worsening kidney injury, dialysis needs, or death. • Semaglutide significantly reduced albuminuria and improved cardiometabolic parameters in overweight/obese patients with chronic kidney disease (CKD) without diabetes. • Tacrolimus demonstrates superior efficacy over mycophenolate mofetil in preventing relapses in children with frequently relapsing nephrotic syndrome.

Ocrelizumab Biosimilar Xacrel Demonstrates Equivalent Efficacy and Safety in Multiple Sclerosis Trial

• A Phase III clinical trial demonstrated that Xacrel, a biosimilar of ocrelizumab, is equivalent to Ocrevus in reducing the annualized relapse rate (ARR) in patients with relapsing-remitting multiple sclerosis (RRMS). • The study, conducted over 96 weeks, showed no significant difference in disability progression, relapse-free rates, or MRI lesion activity between patients treated with Xacrel and those treated with Ocrevus. • Safety profiles were comparable between the two groups, with similar incidences of adverse events, infusion reactions, and immunogenicity, supporting Xacrel as a potential cost-effective alternative to Ocrevus. • The findings suggest that Xacrel could expand access to B-cell-depleting therapy for MS patients, offering a more affordable treatment option without compromising efficacy or safety.

Axatilimab Approved for Chronic GVHD After Failure of Two Prior Therapies

• Axatilimab has received FDA approval for treating chronic graft-versus-host disease (GVHD) in patients who have not responded to at least two prior systemic therapies. • Chronic GVHD can affect almost any organ in the body, leading to significant symptom burden and long-term immunosuppression requirements for affected individuals. • Current GVHD prevention methods, such as calcineurin inhibitors and methotrexate, have reduced incidence rates, but effective treatments are still needed for those affected. • Emerging strategies like graft engineering with platforms such as Orca-T show promise in further reducing chronic GVHD rates, but the disease is unlikely to vanish completely.

NCCN Guidelines Update: Evolving Treatment Landscape for Graft-vs-Host Disease Management

• Oral therapies including ruxolitinib, ibrutinib, and belumosudil have become preferred treatment options for steroid-refractory GVHD, superseding many traditional agents. • Targeted therapies like infliximab show particular efficacy for specific GVHD manifestations, with notable responses in patients with severe colon and liver involvement. • Treatment selection criteria now emphasize route of administration, ease of use, and adverse event profiles, while avoiding agents that cause profound immunosuppression.
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