May 14, 2003
BIRMINGHAM, AL — A UAB (University of Alabama at Birmingham) patient today became the first person in the nation to be administered a new "orphan drug" for Fabry disease that was approved on April 25 by the U.S. Food and Drug Administration (FDA).
Fabry disease is a rare condition in which males are born without an enzyme that breaks down certain fat molecules in the body. The fatty particles may accumulate in various organs, with sometimes devastating consequences. The orphan drug designation provides seven years of market exclusivity for the newly approved enzyme replacement therapy (ERT) named Fabrazyme®, a product of Genzyme Corporation. The orphan drug program is designed to encourage the development of treatments for rare disorders for which no therapies have existed previously.
In the case of UAB patient Doug Morgan, 41, the chief manifestation of Fabry disease is deteriorating kidney function. His physician, Dr. David G. Warnock, director of nephrology at UAB, has been in the forefront of lobbying for approval of an enzyme replacement therapy. Genzyme has designated UAB as a certified infusion center. Warnock, who is the president-elect of the National Kidney Foundation, said UAB is working closely with insurance companies and third-party payers to cover the cost of the treatment. "Because of the extraordinary cost of the therapy, it is essential that such coverage be identified on a case-by-case basis."
"Fabry patients have waited 30 years since research began on ERT, so this is a tremendously fulfilling day for all of them to finally have this available," Warnock said. "We've already begun fielding calls from excited patients from around the state and region who want to take advantage of this new development."
Fabry disease affects about 5,000 people worldwide. The average lifespan of patients is 50 years. Clinical manifestations of the disease in addition to kidney failure may include stroke, heart disease and debilitating pain. Fabry disease is X-linked, meaning that females are carriers of the trait and their male offspring have a 50 percent chance of being born with the disorder.
Fabrazyme is a genetically-engineered form of human alpha-galactosidase A, the enzyme missing in these patients. It is administered intravenously to replace the deficient enzyme and start the breakdown of the clumps of lipids. The drug underwent extensive clinical trials before its approval on April 25.
Morgan, a native of Florence, is a research assistant at the UAB Comprehensive Sickle Cell Center. He has been followed at the National Institutes of Health since 1994, after his diagnosis at UAB. For 15 months he has been traveling back and forth to the NIH campus in Bethesda to receive an enzyme replacement product as part of a clinical trial conducted by a Genzyme competitor.
Although the therapy alleviated some general problems and reduced his pain level, it did not stop his descending kidney function. After the FDA made its choice of products, he chose to switch to Fabrazyme, which is five times more potent than the drug he was on. "My kidney function was continuing to go downhill," he said, "so I want to try to stabilize it before I get to the point of needing kidney dialysis or transplantation."
STATEMENT OF BRIAN PEREIRA, MD, MBA
PRESIDENT, NATIONAL KIDNEY FOUNDATION
"Fabry Disease is a very rare, inherited cause of kidney failure, that primarily affects males. To this date, no therapy has been available to stop the progression of this disease. The availability of replacement enzyme therapy in a triumph of medical research and offers new hope to the patients affected with Fabry Disease. On behalf of these patients, and for all the patients with kidney disease that the National Kidney Foundation represents, I want to convey my heartiest congratulations on the initiation of this therapy.”
STATEMENT OF DR. ROBERT J. DESNICK, PH.D., M.D.
CHAIRMAN, HUMAN GENETICS, MT. SINAI SCHOOL OF MEDICINE (NYC)
DIRECTOR, INTERNATIONAL CENTER FOR FABRY DISEASE
"Congratulations to Dr. Warnock and UAB. Your treating the first patient in the US after FDA approval is another milestone for the many patients who suffer from this inherited disease, and is the sentinel of treatment for the Fabry patients and families who have waited with great anticipation for this day when there would be a safe and effective treatment."
PATIENT BIOGRAPHY: DOUG MORGAN
In 1986 Doug Morgan, now 41, had no idea that he had a serious hereditary disorder called Fabry disease. But as a pre-pharmacy student at Samford University, he began having severe double vision and came to UAB Hospital for help. A dermatology resident noticed sprays of tiny red dots on the back of his hands. This manifestation of broken blood vessels near the skin is indicative of Fabry disease. UAB specialist Dr. Jerry Thompson, currently a professor in the department of human genetics, confirmed the diagnosis. Thompson sent Morgan to the National Institutes of Health in Bethesda, Maryland, for follow up examinations.
Morgan was referred to UAB neuro-ophthalmologist Dr. Lanny Kline, now chairman of ophthalmology, for follow up on the vision problem, characterized by “tortuous vessels” in the eyes. Only a few months later, in June 1986, Morgan suffered a stroke, also a probably consequence of Fabry disease. The 24-year-old was treated at UAB and went home to Florence, Alabama, to recover. “My stroke left my left side impaired, but I eventually recovered most of my function,” he said. “The good news was that my double vision cleared up, probably because of some medicine I took to thin my blood and prevent additional strokes.”
Morgan switched his major to biology and received his bachelor of science degree from the University of North Alabama in 1987. At UNA, he met and married his wife. (Susan is Mother’s Day Out director at Evangel Presbyterian Church in Helena.) They moved to Birmingham after Morgan got a job offer to be a research assistant in the UAB microbiology department. Currently he works for the director of the UAB Comprehensive Sickle Cell Center, performing genetic studies on mice.
“With my biology background and with all the resources of this medical center around me, I’ve been able to learn a lot about my disease,” he said. “Since 1994 I went to the NIH every six months to get checked up. My brother, who’s now 45 years-old, was also found to have the disorder, so he and I would go together for the three days for tests.”
Morgan was left with burning pain in his hands and feet, the inability to sweat (“obviously a major problem in these Alabama summers!”), and for the past few years, declining kidney function. “Because my renal lab values were deteriorating, my primary physician, Dr. Alan Gruman at Kirklin Clinic, referred me to Dr. David Warnock, the head of nephrology,” he said. “Dr. Warnock has really fought to get me into an enzyme replacement program.”
Since Fabry’s disease is an X-linked abnormality, females are the carriers of the genetic disorder and their male offspring each has a 50 percent chance of being born without the crucial enzyme that breaks down certain fatty particles in the body. No other males in his parents’ immediate family have the disease. “Susan and I prayed long and hard about whether to have children, knowing that any girls would be carriers of the disease. Because Susan is not a carrier of Fabry, any sons we had would be free of the disease. But we had daughters, now ages 11 and 8, so that’s something that we will try to help them understand and that they will have to deal with as they make their choices in life.”
When enzyme replacement therapies were going through clinical testing, both brothers were enrolled in the trials of a product that was competing with Genzyme Corp. for FDA approval under the “orphan drug” designation program. This federal process gives pharmaceutical companies incentives to develop drugs that might only be targeted to individuals with disorders so rare that it otherwise would not be financially feasible for these companies to deal with.
“The TKT infusions helped me with some gastrointestinal problems and the burning pain I had in my hands and feet, but did not stabilize my declining kidney function,” he said. “I knew from my reading scientific journals that the Genzyme drug that was also undergoing testing was five times more powerful than the one my brother and I were getting. Because he is doing pretty well on his current therapy, he elected to stay with that, but I desperately want to keep from losing any more kidney function. I think my best shot at this is taking the Fabrazyme from Genzyme now that it is on the market.”