Two UMMS gene therapy clinical trials aided by $2 million from FDA’s rare disease grant program
Two clinical trials currently underway at UMass Medical School have been buoyed by new funding received by the institution’s commercial collaborator, Applied Genetic Technologies Corporation (AGTC). A clinical stage biotechnology company, AGTC received $2 million from the U.S. Food and Drug Administration (FDA) to continue clinical trials aimed at developing novel systems to deliver human therapeutics to treat type 2 Leber Congenital Amaurosis (LCA), an inherited eye disease that causes severe visual loss within the first few months of life, and alpha-1 antitrypsin deficiency, a hereditary disease that impairs respiratory function and can lead to fatal lung and liver complications. Both clinical trials, focused on using an adeno-associated virus (AAV) to deliver corrective genes to patients, are being conducted at UMass Medical School in conjunction with AGTC.
The funding comes from the FDA’s Orphan Products Grants Program, which works to promote the development of products that demonstrate promise for the diagnosis or treatment of rare diseases and conditions. Rare but devastating diseases such as Huntington’s disease or Tourette syndrome affect so few people in comparison to cancer, heart disease and diabetes that commercial funding for expensive and time-intensive clinical trials can be difficult to obtain. The FDA grants bridge the chasm between the financial resources required to bring a new drug to development and the need to bring treatments to patients suffering from these diseases.
A degenerative disease, LCA is caused by a group of recessively inherited genetic mutations that lead to an inability to make a light-sensitive protein in the retina. Funding from the first grant will be used to complete enrollment of a Phase I/II trial to evaluate the safety of using a recombinant adeno-associated virus vector to deliver a normal-functioning gene to retina cells of patients with type 2 LCA. A small virus known to occur in humans, AAV does not cause any known pathology and creates only a mild immune response in its host. Once introduced into cells, AAV has the ability to leave its genome in the targeted cells, making it a potential therapeutic delivery system for transferring normal genes to patients suffering from certain genetic disorders. The UMass Medical School clinical trial is being conducted by Shalesh Kaushal, MD, PhD, chair and associate professor of ophthalmology.
The second grant will be used to complete a Phase II clinical trial to study the safety and effectiveness of using the same recombinant AAV vector to replace a faulty gene that prevents the production of the alpha-1 antitrypsin protein. In people with alpha-1 antitrypsin deficiency, a genetic mutation prevents the production of a protective form of the protein alpha-1 antitrypsin, which is normally produced in the liver and protects the lungs from inflammation. Those lacking alpha-1 antitrypsin are vulnerable to infections or irritants in the air, such as cigarette smoke, and often develop a life-threatening lung disease. In others, the deficiency can lead to emphysema or cirrhosis of the liver, both potentially fatal progressive diseases.
“The tremendous potential of recombinant AAV vector technology to impact human disease symptoms has recently been demonstrated in a number of early phase clinical trials, particularly in the retina and brain. We are excited at the opportunity to determine whether this technology can safely and effectively be brought to bear on genetic emphysema due to alpha-1 antitrypsin deficiency,” said Terence Flotte, MD, executive deputy chancellor, provost, dean of the School of Medicine and the Celia and Isaac Haidak Professor of Medical Education.
“We are thrilled that the FDA and its grant reviewers continue to recognize AGTC’s expertise in clinical development of treatments for rare genetic diseases with these two grant awards,” said Sue Washer, president and CEO of AGTC, which is based in Florida. “The ultimate goal is to improve the quality of life for these patients. We continue to be encouraged by the data from these trials supporting the adeno-associated virus’s ability to provide sustained delivery and expression of therapeutic levels of many different biologics.”
Drs. Flotte and Kaushal are members of the Gene Therapy Center, part of the Advanced Therapeutics Cluster at UMMS. Established around the promise that lies within the application of the recombinant adeno-associated virus, the Gene Therapy Center is performing translational research into cystic fibrosis, alpha-1 antitrypsin deficiency, lysosomal storage diseases, Canavan disease, retinal and macular degeneration, and other genetic diseases.
The FDA has not yet approved gene therapy treatments for any disease.
About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $255 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.
About Applied Genetic Technologies Corporation
AGTC is focused on the research and development of novel therapeutics for patients with unmet medical needs utilizing AGTC’s proprietary, non-pathogenic adeno-associated virus (AAV) delivery system. AGTC has demonstrated that this system can be used to deliver a normal form of a gene in both animals and humans, thus allowing their own body to produce sustained therapeutic levels of important biologics. The company’s most advanced programs in development are treatments for alpha-1 antitrypsin deficiency, a disease causing a progressive loss of lung function, and Leber’s Congenital Amaurosis, an inherited condition causing early blindness. Both utilize AGTC’s proprietary AAV system and production methods. The company is located near Gainesville, Fla, and is financed by the nationally renowned venture firms InterWest Partners, Intersouth Partners, and MedImmune Ventures. For more information see www.agtc.com.
