This is a test version of Biostars. For the public version, visit https://www.biostars.org.
FDA First in Class Designation

What constitutes a First in Class designation for new molecular entities? I've seen this term on FDA documents, as well as in databases(Chembl for example), but I was curious if there are any set criteria for First in Class drugs? The easy definition, in my mind, would be a drug that, hits a novel target given its indication. However, if you look at antifungal drugs, you see that drugs with the same target for the same general indication(anti-fungal) treat completely different fungal infections because of their pharmacokinetics.

Are there discrete criteria for the FDA's first-in-class designation for New Molecular Entities?

pharmacology first-in-class drug discovery
• 26,951 views • link
written by rmoore8869 • rmoore8869

2 answers

First-in-Class means drugs that use a new and unique mechanism of action for treating a medical condition according to FDA 2011 Novel New Drugs).

• 1 views • link
written by Denise CS Denise CS

Do you know when this definition came about? It can't be that new, because in the Chembl Database, chlordiazepoxide is listed as first-in-class, which was first approved in 1960. I'm interested because there are still many drugs for which there are no mechanisms of action. This leads me to believe there might be three categories of drugs:

  1. First-in-Class
  2. Not First-in-Class
  3. Unknown
• 1 views • link
written by rmoore8869 • rmoore8869

Perhaps there are only two. First in class and those that are not.

• 1 views • link
written by GenoMax GenoMax

Between the other that are not, they may be the “advance-in-class” (defined as a non-first-in-class product that receives a priority review designation) or “addition-to-class” according to this article on Nature Review Drug Discovery.

• 1 views • link
written by Denise CS Denise CS

Our Open Targets Platform integrates data from ChEMBL (check this post for a summary of Open Targets), so I've checked with my colleagues from ChEMBL (Paula Magarinos and Anna Gaulton). These are their comments (all acknowledgment to them. For further details please contact the ChEMBL help):

Blockquote

  • a) There may not be a single, clear definition;
  • b) ChEMBL considers the first drug for a particular mechanism of action to be first in class (regardless of the indication);
  • c) Other people might also consider the indication - so they would consider a drug first in class if it was the first time that mechanism had been used for a particular disease, even if the mechanism was already used for something else.
  • d) things get complicated if c) applies as as ones needs to decide what is a new disease (e.g., is every type of cancer a new disease and therefore a drug could be first in class even though the target is used in several other cancers already? Similarly with the anti fungal example. Also one would need to consider updating older drugs if they are repurposed.
  • e) More complications: is the first antibody for a target first in class even if there are small molecules already? What if it is the first selective agent for a particular target, but there were previously non-selective drugs for the target class?
  • f) Despite ChEMBL's fairly simple definition, there are cases that are difficult to classify. e.g., kinase inhibitors (if a drug interacts with some of the same kinases as other drugs, but also some novel ones, do we say it’s first in class?)
  • g) and at last but not least, in ChEMBL the first in class annotation comes from manual curation in the case of old drugs. For new approvals, if the drug is the first to act on a particular target according to the information in ChEMBL, it will be annotated as first in class.

Blockquote

• 1 views • link
written by Denise CS Denise CS

Log in to answer this question.

More posts like this