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Potential catalysts in therapeutics.

Bruce A Luxon¹

¹Division of Gastroenterology-Hepatology, University of Iowa, Iowa City, IA.

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

|August 29, 2014

Summary

New immunosuppression drugs are scarce, with focus on reducing side effects from steroids and calcineurin inhibitors (CNI). Emerging antibody therapies show promise for specific transplant patients, but widespread availability is years away.

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Area of Science:

Immunology
Transplantation Medicine
Pharmacology

Background:

Significant advancements in immunosuppressive drug development have been limited over the last decade.
Current research focuses on mitigating side effects associated with corticosteroids and calcineurin inhibitors (CNI).

Purpose of the Study:

To review the current landscape of immunosuppression in transplantation.
To explore emerging therapeutic strategies, including novel antibodies targeting costimulatory pathways.

Main Methods:

Analysis of the current pharmaceutical pipeline for immunosuppressive agents.
Review of clinical trial designs focusing on steroid or CNI withdrawal and the use of mTOR inhibitors.
Examination of the development and investigation of new antibody therapies in transplantation.

Main Results:

No new CNI drugs are anticipated, though extended-release tacrolimus is available.
Clinical trials are primarily investigating the withdrawal or substitution of existing immunosuppressants like steroids and CNI with mTOR inhibitors.
New costimulatory pathway-blocking antibodies are approved or under study for kidney and liver transplantation, with initial research in other immune-mediated diseases.
These novel antibodies are unlikely to be widely available within 2-3 years.

Conclusions:

The development of novel immunosuppressive drugs remains slow, with a focus on optimizing existing therapies.
Emerging antibody therapies targeting costimulatory pathways represent a promising, albeit specialized, future direction in transplantation.
These newer agents may offer benefits for specific patient populations, such as those with hepatocellular carcinoma (HCC) or hepatitis C virus (HCV) infection, where risk-benefit profiles are favorable.