For several years a company initially called Advanced Magnetics (and later known as AMAG Pharma), with its partners, spent a good deal of money developing and seeking approval of a product called ferumoxtran-10.
Ferumoxtran-10 was an imaging agent that, when used in combination with magnetic resonance imaging (MRI), appeared to be able to make visible, with considerable accuracy, the presence of cancer-containing lymph nodes in patients with progressive prostate cancer. In Europe the brand name from feromoxtran-10 was Sinerem; in the USA it has long been known as Combidex.
Back in June last year, we had commented on a then-recently published study that seemed to throw some light on why Combidex (although approved in some European countries) had never succeeded in gaining approval in the USA.
The precise situation was as follows:
- In June 2000 the U. S. Food and Drug Administration (FDA) issued an approvable letter for Combidex requesting additional information.
- Advanced Magnetics submitted a complete response to the approvable letter; this was accepted by the FDA, and an Oncology Drugs Advisory Committee (ODAC) hearing was held on March 3, 2005.
- In Europe, a product dossier (the European equivalent of a NDA) was submitted to the European Medicines Evaluations Agency (EMEA) in December 1999.
Ferumoxtran-10 was subsequently approved for clinical use in some European countries. In late 2003 a paper by Harisinghani et al. in the New England Journal of Medicine offered extraordinary images of the way in which ferumoxtran-10 could demonstrate the presence of positive lymph nodes in patients with prostate cancer. Additional, detailed information about ferumoxtran-10 and its clinical use from 2004 is available on the web site of the Prostate Cancer Research Institute. However, ODAC voted 15 to 4 not to recommend approval of the proposed indication for this drug in the USA, stating that there were insufficient clinical data to support a broad indication for use of ferumoxtran-10 to differentiate metastatic from non-metastatic lymph nodes across all cancer types.
For many years there have been small numbers of patients who would travel to the Netherlands to get their lymph nodes checked using ferumoxtran-10. However, the maufacturer terminated production of the product several years ago. In an e-mail to Chuck Maack just recently, Prof. Jelle Jelle Barentsz of the Department of Radiology at the University of Nijmegen in Holland apparently wrote:
Yes I confirm. There is no contrast anymore anywhere in the world, because AMAG Pharma decided to stop the production 5 years ago. Combidex MRI stops next week on April 1st.
I am working on solutions.
As we wrote in our prior article, the development of a “second generation” imaging agent based on the science used to develop fermoxtran-10 would seem to be a promising opportunity. Ferumoxtran-10 seems to have had some relatively small underlying flaws, and in the USA the manufacturer may have been unwilling or unable to focus product development and approval on a limited indication that might well have been approvable.
We desperately need better tests that can be used to accurately detect the presence of prostate cancer once it has escaped from the prostate into other organs. It would seem all too sad if the research on ferumoxtran-10 cannot be used as the basis for another attempt to develop a a new imaging agent with a comparable safety profile and a slightly better effectiveness profile.