zondag 5 februari 2012

Nieuw medicijn tegen het syndroom van Dupuytren


Triumph for Drug to Straighten Clenched Fingers

It took half a century. But a tiny drug maker on Long Island has finally found a potentially lucrative use for its only medicine: straightening clenched fingers. And, if research proves successful, treating a condition that causes bent penises.
The Food and Drug Administration approved the drug, known as Xiaflex, last month as a nonsurgical treatment for Dupuytren's contracture, a condition in which one or more fingers cannot be straightened.
Hundreds of thousands of Americans have Dupuytren's, which can make it difficult to type, shake hands, wear gloves, reach into a pocket or perform numerous other tasks. The afflicted have included Ronald Reagan,Margaret Thatcher, the playwright Samuel Beckett and the classical pianist Misha Dichter.
Xiaflex, an injectable drug that goes on sale later this month, will not be cheap, at an estimated average cost per course of treatment of $5,400. But analysts expect sales to reach hundreds of millions of dollars a year.
And that total could go higher, if Xiaflex eventually wins approval for a related condition known as Peyronie's disease, in which a bent penis makes intercourse painful or even impossible.
About one in 20 men is estimated to have Peyronie's, but figures are not precise because people with the condition tend not to discuss it publicly.
Although the company selling Xiaflex will be Auxilium Pharmaceuticals of Malvern, Pa., the F.D.A. approval was a belated triumph for the drug's original developer, BioSpecifics Technologies of Lynbrook, N.Y., on Long Island. Founded in 1957, it struggled for decades to find uses for the product, almost going out of business before licensing the drug to Auxilium in 2004.
“It sort of proves to people that if you really believe in a drug you should never give up,” said Matthew Geller, a biotechnology investment banker who is a member of the BioSpecifics board.
Shares of BioSpecifics closed Monday at $27.61, up from $1 as recently as late 2006.
Some people treated with Xiaflex in clinical trials for the Dupuytren's hand condition said it had made a big difference in their lives, and had allowed them to avoid painful surgery. "When I looked down and saw my finger straightened out, I cried",  said Kenneth Nelson, 65, of Indianapolis. "It was to me just like a miracle."
Xiaflex is an enzyme produced by a gangrene-causing bacterium, Clostridium histolyticum, which uses it to eat away the tissues of its victims. The enzyme, called collagenase, breaks down collagen, a major component of the body's connective tissue that is found in skin, tendons, cartilage and other organs.
But collagenase by itself does not cause gangrene. And there are times doctors need to break down collagen, such as when an excess builds up in the hand or penis, causing Dupuytren's and Peyronie's. The ailments are named for French surgeons who described the conditions in the 18th and 19th centuries.
The enzyme was first extracted from the bacteria around 1950 by Ines Mandl, a young biochemist at Columbia University. Edwin H. Wegman, a Long Island entrepreneur, learned about Dr. Mandl's work and set up a company called Advance Biofactures, which later became BioSpecifics, to turn collagenase into a drug.
In 1965, the company won approval of an ointment containing collagenase for use in removing dead tissue from skin ulcers and burns. The ointment, sold by licensees under the name Santyl, was a modest success, but the company never truly prospered.
So in the 1970s the company began developing what it thought would be a bigger money-maker, an injectable collagenase. It tested that drug for numerous uses, including herniated disks. Finally, in the early 1990s, two professors of orthopedics at the nearby State University of New York at Stony Brook suggested using the drug for Dupuytren's.
The professors, Dr. Lawrence C. Hurst and Marie A. Badalamente, injected the drug into the tails of rats, as a stand-in for human fingers. They found they could dissolve the collagen in tendons, making the tails floppy, without harming nearby nerves and arteries. Then they organized clinical trials in patients and got federal grants to help pay for the work. The professors and Stony Brook will share a royalty of one half of 1 percent of sales of Xiaflex for use in treating Dupuytren's.
But work was slowed by lack of money, and by 2004, BioSpecifics was about out of cash. In desperation, Ed Wegman's son Mark, a top computer scientist at I.B.M., called a childhood friend, Laurence Korn, who had been the chief executive of a successful biotechnology company now known as PDL BioPharma.
With Dr. Korn's help, BioSpecifics licensed the drug to Auxilium in a matter of weeks, receiving $5 million initially.
Auxilium was interested because of Peyronie's disease. It already was selling a gel for men with lowtestosterone and had learned from urologists about the need for better treatments for bent penises.
“From talking with surgeons and patients who have Peyronie's, neither of them wants to do the surgery,” said Will Sargent, a spokesman for Auxilium.
Two years ago, the drug giant Pfizer, which sells the erectile dysfunction drug Viagra, licensed the European rights to Xiaflex from Auxilium for an initial payment of $75 million. BioSpecifics got $6.4 million of that amount and will receive 8.5 percent of additional payments of up to $410 million that Pfizer might make.
Auxilium sought approval for treating Dupuytren's first because it was easier to measure success in straightening fingers. But the company hopes to begin late-stage trials of Xiaflex for Peyronie's disease later this year. In a midstage trial, injections of Xiaflex into the collagen plaque in the penis reduced the curvature. But the drug did not reduce pain or discomfort during intercourse by a statistically significant amount.
While collagenase itself is not patented, the companies do have patents on the use of the enzyme to treat Dupuytren's and Peyronie's. They are also shielded from competition for seven years under a federal law aimed at spurring development of drugs for rare diseases, even though newer estimates suggest these two diseases are not as rare as thought when the drugs were given orphan status.
Auxilium and BioSpecifics hope that the half-century-old collagenase might eventually become as versatile asBotox, another bacterial product. They are looking at uses that range from loosening up immobile "frozen shoulders" to eliminating fat bulges and cellulite.
With its belated success, BioSpecifics has sold off its ointment business. It now has only five employees and a business of collecting a roughly 11 to 12 percent royalty on sales of Xiaflex.
"We will be a cash machine going forwardz", said Thomas L. Wegman, the president and the other son of the company founder. "We don't have to pay for marketing. We don't have to pay for manufacturing."
The Wegman family - the two sons and the founder's 75-year-old wife, Toby - controls about 25 percent of the company's stock.
Ed Wegman, the company's founder, did not live to see the F.D.A. approval, dying at age 87 in 2007. On Feb. 2, the day the drug was approved, one BioSpecifics director sent an e-mail message to the others saying, "Well done. Hope Ed is looking on."
Meanwhile, Dr. Mandl, the biochemist who first isolated collagenase from the bacteria, is nearing 93. Last year, when BioSpecifics stock rose above $30, she sold the last 1,000 shares she had been given for serving as a consultant to the company over the years.
Unfortunately, she had sold most of her holdings years earlier for a relative pittance. "If I still had what I originally had", she said. "I'd be very rich."

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