In November 1998, the U.S. Food and Drug Administration approved one of most anticipated drugs in medical history: Enbrel. It was aimed at treating rheumatoid arthritis.
What was so widely anticipated about Enbrel, made by a Seattle company called the Immunex Corporation, was that it was designed specifically to limit the effects of an overreactive immune system without undermining the entirety of the system.
It was built around the discovery of monoclonal antibodies in the seventies. The ability to isolate and replicate individual antibodies was allowing drugmakers to develop medicines constructed around very specific molecules. These antibodies, injected into the body, would theoretically attach to and react with only very specific cells in the body.
For instance, Enbrel works by using monoclonal antibodies to interact with a particular cytokine—an immune system signaler—known as tumor necrosis factor, or TNF. What TNF does is send a signal that causes a cell to die, specifically by experiencing apoptosis. This is a crucial normal process in our Festival of Life, and it is quite elegant and orderly. A cell receives a signal to die, essentially to kill itself, and it begins to break into little digestible chunks that then get eaten by the janitors, the macrophages. (Apoptosis comes from a Greek word meaning a falling off.)
With Enbrel and other drugs that act on TNF, the idea is to get the cells that are causing problems to commit suicide. Obviously, getting malignant cells to off themselves can be useful in cancer. In the case of rheumatoid arthritis, it’s also advantageous to have overzealous immune cells commit apoptosis. Instead of attacking Linda’s body, the cells would kill themselves.
(Heady stuff, and even weirder given another bit of trivia: The monoclonal antibody used in Enbrel is produced in hamster ovaries.)
Dr. Lambert couldn’t wait for Enbrel to come out. “It was a game changer. We all knew that. We were waiting for it.”
In early 1999, Linda took her first infusion of Enbrel via a shot in her upper thigh. It took several months to work, and then . . . whoa.
The swelling began to subside. The pain began to diminish.
Enbrel wasn’t scorching the earth of Linda’s immune system, as steroids could do, but acting in a more targeted fashion. This was part of the dream of immunology, going back to Jacques Miller—to understand the immune system well enough to tinker with it.
“My immune system is allowed to work, and this binds to the parts of my immune system that are attacking me and neutralizes them,” Linda said, sounding awed. “Once I went on this drug, my life just changed.”
Enbrel is now one of the bestselling drugs in the entire world. It generated $5.5 billion in sales in the 2017 fiscal year for Amgen, the company marketing it.
The story of how these drugs work is even more sensational when it comes to cancer, and I’ll tell you that story shortly.
But this is not pure miracle. Autoimmunity is too complex for one size fits all, and the new drugs still leave many people feeling invisible.
This brings us to Merredith Branscombe—both an echo of Linda and a study in contrasts.