BREWING HOPE FOR TRANSPLANTS

[Guest guest]

Brewing Hope for Transplants

Tuesday, February 24, 2004

It's a vicious cycle.

Doctors give transplant patients anti-rejection drugs to suppress the immune system, protecting the new organ from the body's natural defenses. But the drugs pose dangers of their own. They inflict damage to organs, both transplanted and healthy; they cause other serious diseases, including lymphoma and skin cancer; and they leave the body exposed to dangerous infections.

As doctors learn more about balancing these hazards, patients live longer. Yet the result is often even more side effects, like thickening of blood vessels in transplanted hearts and long-term, chronic rejection.

``It's always been the hardest part,'' said Dr. Rohrer, chief of the transplant division at Tufts-New England Medical Center in Boston. ``In the beginning, we were in an era when so few people survived the transplant, they didn't live long enough to see these side effects and other organ damage.''

Despite the trade-offs, a handful of pharmaceutical manufacturers are competing to get their products into the increasingly complex drug cocktails that patients must take to prolong their lives. One obvious incentive: sales of anti-rejection drugs currently add up to a $3 billion market, which is expected to grow.

With patients living longer, the estimated number of organ transplant patients needing treatment worldwide will grow to 700,000 by 2010, up from 440,000 now.

The standard anti-rejection drug treatment for two decades has been a combination of cyclosporin and steroids. Much of the effort to develop and market new drugs is aimed at prolonging survival while protecting kidneys and other organs from the side effects.

``You're always walking that razor's edge between giving too much drug and damaging the kidney and not giving enough and having the transplanted organ rejected,'' said T. , chairman and CEO of Isotechnika Inc., a Canadian biotechnology company.

Isotechnika has a $215 million licensing agreement with Hoffman-La Roche Inc. to develop an improved version of cyclosporin, which it says will be more potent and less toxic. Roche would like a better cyclosporin to use in tandem with its blockbuster CellCept, another immunosuppressant that was approved in 1998 for kidney transplants and is becoming a key weapon in fighting rejection of other transplanted organs.

Novartis International AG holds the largest market share for cyclosprorin, under the brand name Neoral, with revenues of about $1.1 billion a year.

Although sales growth for Neoral is flat, as physicians seek alternatives, Novartis has at least three new drugs under development. One, Myfortic, is designed to compete head to head with Roche's CellCept. Another, Certican, was approved in Europe in 2003 and is expected to be approved in the United States this year.

A third drug under development by Novartis, still known by the code name FTY720, causes less damage to the kidney than standard treatments by selectively excluding the immunosuppression effect. It will not be on the market until at least 2007, according to Novartis.

``The leaders in this field are Novartis and Roche; both of them are spending heavily and expanding in this area,'' said Shaojing Tong, a pharmaceutical analyst with Mehta Partners LLC in New York. ``If you can develop a really good drug, this market can grow significantly, because this problem is not really solved.''

Roche's CellCept grosses about as much as Neoral, but sales growth is in the 25 percent range, said Tong. Another standard treatment, Prograf, marketed by Fujisawa USA, grosses about $300 million to $400 million a year, according to Tong. A half-dozen other drugs, led by Wyeth Pharmaceuticals Inc.'s Rapamune, make up the remainder of the market.

In addition to the chemical molecules developed by their pharmaceutical researchers, Novartis and Roche also market biotech drugs. Both have monoclonal antibody treatments developed from mouse cells.

Tony Rosenberg, Novartis global business unit head for transplant drugs, said kidney and liver transplants will continue to create demand for drugs.

He predicted there will be plenty of room in the market for competing formulations, as doctors continue to experiment on ways to fight one of the toughest problems in medicine.

``The problem is when an organ is rejected, your body is doing exactly what it should do,'' he said. ``You're trying to fool about 4 billion years worth of evolution.''

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