A first-in-kind immune-modulating drug that arose from decades of basic research at UT Southwestern Medical Center has received approval from the U.S. Food and Drug Administration as a new treatment for adults with a form of myasthenia gravis. This rare and chronic autoimmune disease is characterized by debilitating and potentially life-threatening muscle weakness.
The new drug, efgartigimod alfa-fcab, is an engineered fragment of a human antibody that binds to a cell surface receptor known as the neonatal Fc receptor, or FcRn. Between 1990 and 2015, former UTSW Professor of Immunology E. Sally Ward, Ph.D., led work that characterized this receptor’s role in regulating the levels and persistence of immunoglobulin G (IgG) antibodies. In 2005, her laboratory described an approach to lower antibody levels by blocking FcRn activity, and subsequently demonstrated preclinical proof-of-concept to treat antibody-mediated autoimmune disease. The global immunology company argenx has licensed exclusive patent rights related to this drug from UTSW.
“The development of this FcRn inhibitor came out of the fundamental work on FcRn biology that my group had worked on during the decades that I was on the UTSW faculty,” said Dr. Ward, now a Professor of Molecular Immunology and Director of Translational Immunology at the University of Southampton in England. “Working out the molecular and cell biological processes involved in FcRn biology and its regulation and transport of antibody molecules was a major focus of our work at UTSW over more than two decades, starting when I was an assistant professor there.”
Clinical trials that led to the recent FDA approval found that 68% percent of patients with anti-acetylcholine receptor antibody positive myasthenia gravis responded to efgartigimod, compared to 30% of those taking a placebo. The company is exploring possible uses for the agent in other conditions mediated by IgG.
Efgartigimod represents Dr. Ward’s second commercial success based on fundamental research conducted at UTSW. That work also led to technology that can extend the half-life of therapeutic antibodies and currently is used in the FDA-approved drug ravulizumab and two antibody therapies against COVID-19, as well as another antibody in development to treat respiratory syncytial virus (RSV).
It is also the second first-in-kind drug developed from basic research at UTSW to be approved by the FDA in the past year. Less than six months ago, belzutifan, a HIF-2α inhibitor, received approval as a treatment for familial kidney cancer.
“Considered together, these approvals mark UTSW as one of the major sources of breakthrough medicines for previously untreatable diseases. We are indeed a center for biotechnology,” said Michael Brown, M.D., Professor of Molecular Genetics and Internal Medicine and joint recipient of the 1985 Nobel Prize in Physiology or Medicine with research partner UTSW colleague Joseph Goldstein, M.D. Dr. Brown helped recruit Dr. Ward to UTSW in 1990.
UT Southwestern receives financial compensation from argenx for the newly approved drug’s foundational intellectual property. Dr. Ward also receives compensation related to the licensing of the technology and research funding from the company.
Both Drs. Goldstein and Brown are Regental Professors.
Dr. Brown holds The W. A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research and the Paul J. Thomas Chair in Medicine.
Dr. Goldstein holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research and the Paul J. Thomas Chair in Medicine.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.