August 29, 2008
Bioengineered Drugs Heal, but at a Big Cost
By Carol M. Ostrom
BOTHELL, Wash. - They are the sturdy, docile workhorses of the biotech revolution: Chinese hamster ovary cells, microscopic living factories that churn out proteins that eventually become drugs such as Enbrel, Amgen's blockbuster treatment for rheumatoid arthritis.These cells start their journey in small flasks, swirling in a nutrient broth that looks like orange Kool-Aid. For weeks, the genetically modified "CHO" cells will be gently encouraged to reproduce - and they do, doubling in number every day. The newborn cells will be pampered with just the right food, temperature and amount of oxygen, and be protected from invading microorganisms.
CHO cells that produce Enbrel spent years at Amgen's Bothell plant, where scientists learned how to keep them healthy and reproducing.
Now their cellular offspring are hard at work in a two-story, 20,000-liter stainless-steel tank in Rhode Island, cranking out a protein that will be sold as Enbrel, treatment for a disease that is twisting and crippling the joints of 2.1 million Americans.
The journey - complicated, delicate and hard to re-create - is one reason why Enbrel, and other new-generation bioengineered drugs, are so expensive.
Enbrel costs about $1,500 a month.
Since the drug was approved for use in 1998, other bioengineered drugs for rheumatoid arthritis, multiple sclerosis, cancer and other diseases have come to market, all made possible by the same breakthroughs in molecular biology. For many patients, these drugs have proved near-miraculous..
Rheumatoid arthritis is a nasty disease. Un-checked, the inflammation, destructive changes to joints and dissolution of bone it causes - along with the pain - can lead to disability, lost work time and the need for orthopedic interventions.
In the mid-1980s, injections of gold salts and methotrexate pills, along with anti-inflammatory medicines such as aspirin, ibuprofen and steroids, were all doctors had to offer.
For most patients, gold wasn't very helpful, and not much was known about its long-term use. Methotrexate got better results, but there could be "significant liver toxicities," noted Dr. Philip Mease, a Seattle rheumatologist. And neither completely stopped the underlying disease from progressively damaging joints.
"I can't even believe what we thought was pretty good at the time," Dr. Mease said.
The "quiet revolution in the field of molecular biology and molecular immunology" changed all that, said Dr. Mease, director of rheumatology research for Swedish Medical Center. Scientists gained a much better understanding of the basic mechanisms underlying arthritis - why immune cells start attacking the body they are intended to protect.
Enbrel, developed by Immunex in Bothell, was approved in 1998. Amgen, based in Thousand Oaks, Calif., bought Immunex four years later. Production of Enbrel takes place at labs in Bothell, Interbay and Rhode Island.
Early on, Dr. Mease was surprised by Enbrel's effect on rheumatoid arthritis and psoriatic arthritis.
"We were able to dramatically help patients," he said. Best of all, X-rays of joints showed that in many cases, the drug was significantly inhibiting - or even stopping - the disease's progressive damage. People were saying, 'You've given me back my life.' 'I can get back to work.' It was quite impressive."
In Greenwich, R.I., Amgen has invested more than $1.5 billion in a campus that includes Enbrel's "mammalian protein" manufacturing facility.
There, the protein spit out by CHO cells in the tank undergoes a final series of purifications and filtrations, delicate processes conducted under scrupulously sterile conditions. All along the way, tests confirm quality and purity - or the batch is scrapped. If all goes well, what's left from that huge tank - a fraction of its original volume - will be sold as Enbrel.
The payoff for Amgen has been enormous.
Last year, Amgen's Enbrel sales in North America totaled $3.2 billion.
Dr. Jim Thomas, vice president of Amgen's process and product development, said scientists have been working for 17 years to improve the production of Enbrel.
But when Amgen tried to make it in a more cost-effective way, the end product was slightly different, and Amgen scrapped the project. "It wasn't Enbrel," Dr. Thomas said. "If you can't make it identical, then you don't know what the safety of that molecule is without doing clinical studies."
And that would increase the price.
Originally published by Carol M. Ostrom The Seattle Times.
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