What’s the definition of a New Chemical Entity? A new chemical entity (NCE) is, according to the U.S. Food and Drug Administration, a drug that contains no active moiety that has been approved by the FDA in any other application submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act. This might seem pretty straightforward, but Keryx are currently finding that there are issues. Keryx (as you may have read in the news feeds) are having worries over the potential exclusivity of their new drug, Zerenex, as the active ingredient may not be distinct enough from Otsuka’s FerriSeltz, approved more than 15 years ago (according to IPD Analytics) – and this piqued my curiosity.
So, what is the definition of an “active moiety”? Again, from the FDA website: “An active moiety means the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance.” Let’s look at the two compounds that are under scrutiny.
Fig 1: 2D chemical images of Zerenex and FerriSeltz active ingredients
Fig 2: Summary matrix from SIP ToxPath knowledgebase, of associations between either FerriSeltz (ferric ammonium citrate) or Zerenex (ferric citrate) and biomedical observations, systematically extracted from Medline, regulatory documents, and public domain toxicology databases, and formatted into assertional metadata, for rapid search and analysis.
If you look at the structures (Fig.1), you can see the potential similarity. However, the two indications are very different – FerriSeltz was approved for upper gastrointestinal enhancement during MRI; Zerenex aims to lower blood levels of phosphorous in patients undergoing kidney dialysis. The two compounds also have quite different biological “fingerprints” (Fig 2), looking at the range of effects on various biomedical observations, reported across current and historic key public domain data sources. Looking at the tissue effects of the two active ingredients again gives a different summary matrix (data not shown). For example, from the biological effects matrix, it can be seen that there are only a few effects that both compounds have in common (effects on ferritin biosynthesis, iron level, oxidative stress) and many effects where there is no overlap (e.g. ALT and AST levels). These data provide more insight into the two different compounds, and hint to possible paths for further investigations.
Meanwhile, I await with interest the outcome of the FDA deliberations – as I am sure, so do Keryx.
I attended a virtual conference last week, hosted by the