What constitutes FDA's First in Class designation for New Molecular Entities?

Question

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?

Answer 1

1. Pharmaceutical performance for all novel therapeutics approved by the FDA between 2005 and 2012 was evaluated using a framework established by the FDA to classify the degree of innovation:
2. first-in-class
3. advance-in-class
4. addition-to-class.
5. Although innovation can be measured in different ways, drugs with novel mechanisms of action (first-in-class) are largely considered to be the most innovative.
6. Drugs that provide important clinical benefits despite not being mechanistically novel (advance-in-class) may be equally important innovations in terms of their clinical promise.
7. The report compared the use of priority review and accelerated approval regulatory pathways, regulatory review times, and characteristics of pivotal trials, including number, design, primary end point, duration, and size, for novel therapeutics stratified by degree of innovation.
8. Between 2005 and 2012, the FDA approved 188 novel therapeutics:
9. 70 (37%) first-in-class
10. 42 (22%) advance-in-class
11. 76 (40%) addition-to-class.
12. Over half of the biologics (56%, 19 of 34) were first-in-class
13. Nearly half of the small molecules (46%, 70 of 154) were additions-to-class and accounted for 73% (51 of 70) of first-in-class therapeutics.
14. Almost two-thirds of therapeutics approved for autoimmune and musculoskeletal diseases (64%, 7 of 11) were first-in-class, as were one-third of therapeutics for cancer (36%, 14 of 39) and less than one-quarter of therapeutics for psychiatric disease (22%, 2 of 9).
15. The authors concluded that the FDA was consistently applying existing regulatory levers to support and accelerate the review and approval of drugs considered mechanistically innovative (i.e., first-in-class therapeutics) as well as those antici- pated to provide substantial clinical advances (i.e., advance-in-class therapeutics acting through existing mechanisms of action).

Eder, J., Sedrani, R., and Wiesmann, C. (2014) The discovery of first-in-class drugs: origins and evolution. Nat. Rev. Drug Discovery, 13 (8), 577–587.