Hi David:
I have thoroughly enjoyed your thoughts under “Rheuminations” in The Rheumatologist and will greatly miss them, particularly your rambling travelogues.
However, I must point out an error in your essay in the December 2011 issue that involves me. You state, “although IL-1Ra was conceived initially as a sepsis drug, it got its first approval for rheumatoid arthritis.” The last part of this statement is correct but the first part is in error.
After my laboratory observed IL-1 inhibitory bioactivity in the supernatants of monocytes cultured on adherent IgG in 1984, for three years we were unsuccessful in purifying the protein because of a loss in bioactivity during chromatography. In 1987, I formed a scientific collaboration with scientists at Synergen, a biotech company in Boulder, specifically to purify the protein from monocyte supernatants prepared by my lab, and to clone and express the cDNA to perform studies on RA.
Synergen hired Chuck Hannum, a protein chemist from the Kappler/Marrack lab at National Jewish specifically for this task. He was successful after two years primarily because he added liberal amounts of a proprietary elastase inhibitor to all of the buffers used for the columns. After large amounts of recombinant protein were obtained, Synergen fired Chuck Hannum and started clinical trials in RA.
However, the investors convinced the executives of Synergen that they needed to evaluate the agent for a disease with a more rapid outcome. RA studies were too slow to yield a quick profit. Thus, they picked sepsis syndrome, against the advice of their external medical advisory board. These trials failed and Synergen collapsed, with the executives escaping with multimillion-dollar golden parachutes. Synergen was purchased by Amgen for the value of their real estate in Boulder.
Fortunately, Amgen continued the RA trials under pressure from me and others. These were ultimately mildly successful and a drug was approved for RA in 2000; although, as you know, IL-1Ra is much more efficacious for autoinflammatory diseases.
William Arend, MD
Professor of Medicine
Rheumatology Division
University of Colorado Health Sciences Center
Aurora
