New Therapy to Restore Hand Function Moves Closer to Approval
A unanimous decision by an FDA advisory committee on Wednesday, September 16, 2009, paves the way for full approval of a novel and noninvasive treatment to restore hand function (and quality of life) for people with the potentially disabling condition called Dupuytren’s (DEW-peh-trins) contracture. The strong endorsement is based on clinical trial results published earlier this month showing injections of an experimental drug that helped straighten disfigured finger joints in two-thirds of the study participants.
Dupuytren’s affects as many as 27 million people in the United States and Europe and tends to run in families. Over time, a rope-like cord of collagen forms under the skin and around the tendon of a finger, bending it toward the palm and “locking” it in place.
Ken Nelson, who—along with his 91-year-old father and 30-year-old son—has Dupuytren’s, was unwilling to gamble on conventional surgery to treat the condition. He first noted unusual growths developing in the palm of his left hand in the early 1960s.
“I was eventually referred to the Indiana Hand Center, and they knew almost immediately that I had Dupuytren’s,” Ken tells the Post. “The doctor described extensive surgery to open up the palms of the hands and delicately remove the abnormal tissue. I basically fled.”
Over time, his condition progressed.
“About 10 years ago, the problem also appeared in my right hand,” Nelson recalls “The small fingers and the ones next to them began to contract to the point that the tips of my fingers were jammed into the palm of my hand. Both thumbs also began to bend over.
“It was very disruptive to me. I could no longer play the piano, which I enjoy. Putting on a pair of gloves became almost impossible. I had to hunt and peck at the keyboard and even bought a voice-activated program so that I could write by speaking into a microphone on my computer. But I continued to tell my doctors, ‘Maybe one day medical science will develop something that is not going to be as intrusive as surgery.’ It was a trade-off for me, and I decided to not do anything.”
Recently, Ken’s wife saw a notice in the local newspaper seeking candidates to test an injectable treatment for Dupuytren’s. He applied, went through the lengthy approval process, and was accepted into the study.
During the experimental procedure, doctors inject Xiaflex (collagenase clostridium histolyticum made by Auxilium Pharmaceuticals) into Dupuytren’s cords in the hand, taking care to avoid the surrounding area. The cord gradually weakens and then ruptures, releasing the tendon and helping to restore the finger’s normal position and movement.
“Dr. Thomas Kaplan injected one cord in my left hand,” Ken reports. “The next day, he started to gently pull back on the affected finger. I felt a stinging sensation and then heard the cord popping and snapping. I had to look away. But then he said, ‘OK, we’re done. I’m happy.’ I looked at my hand, and, for the first time in 10 years, my finger was straight. I got tears in my eyes and hugged the doctor. It was like a miracle to me.”
Phase III data show the promising treatment significantly reduced the angle of contracture of the finger joint closest to the palm of the hand (called the metacarpophalangeal or MP joint) and the middle joint (or proximal interphalangeal or PIP joint), regardless of severity. Multiple treatments may achieve the best results.
“Xiaflex is an enzyme that comes from the bacterium called Clostridium histolyticum,” study investigator Dr. Thomas Kaplan, who treated Ken Nelson at the Indiana Hand Center in Indianapolis, explained to the Post. “In Dupuytren’s disease, multiple fibers of collagen run along the cord. When the enzyme is injected into the cord, it starts ‘cutting’ the fibers into progressively smaller fragments, weakening the cord in that section.”
Investigators believe that many patients with Dupuytren’s may benefit from the first-in-its-class treatment option. Early intervention may prove to be the most effective approach.
“Multicenter study results published in The New England Journal of Medicine show that 89 percent of MP joints with contracture less than 50 degrees were fully corrected, and 81 percent of PIP joints less than 40 degrees were fully corrected by the experimental treatment,” explains Dr. Kaplan, who is also clinical assistant professor of orthopaedic surgery at Indiana University School of Medicine.
A final FDA decision on Xiaflex is expected within three months. Once approved, experts predict the drug could hit the market next spring.
“Hopefully, this research will represent a whole new treatment paradigm for Dupuytren’s that will be more tolerable and provide patients a better experience than we have been able to offer them with surgery,” adds Dr. Kaplan. “It is really exciting.”
Nelson, now 65, enthusiastically agrees.
“I can play the piano again,” he says. “A quality of life has been returned to me that I had never expected to experience again. I am thrilled with the outcome and my wife is happy too—I can do more chores!”