New data from Celgene Corp. (NASDAQ:CELG) showed that a metabolite of ozanimod accounted for the "majority" of the total activity of the relapsing multiple sclerosis candidate in humans. The revelation may provide a clue as to why FDA issued a refusal to file letter to an NDA for ozanimod in February. According to Celgene, FDA said the non-clinical and clinical pharmacology sections of the NDA were "insufficient to permit a complete review" (see BioCentury, March 2).
In a presentation at the American Academy of Neurology meeting in Los Angeles, Celgene said ozanimod and its major active metabolite, CC112273, showed similar potency and selectivity for ozanimod’s targets, sphingosine 1-phosphate receptor 1 (S1PR1; S1P1; EDG1) and S1PR5. While the metabolite accounted for the majority of the total activity of ozanimod in humans, CC112273 was only a minor metabolite in non-clinical studies in animals, according to a slide in the presentation.
FDA guidance published in 2016 states that the “discovery of disproportionate drug metabolites late in drug development can potentially cause development and marketing delays” and that “human metabolites that can raise a safety concern are those formed at greater than 10 percent of total drug-related exposure at steady state.”
Celgene did not respond to an inquiry as to whether the discovery of CC112273’s activity in humans led to FDA’s February refusal to file, or with the company's next steps.
The NDA was based on the Phase III SUNBEAM and RADIANCE trials in which oral ozanimod met the primary endpoints of both trials (see BioCentury Extra, Oct. 30, 2017).
Earlier this month, Celgene announced COO Scott Smith left the company and that his responsibilities would be assumed by CEO Mark Alles (see BioCentury Extra, April 2).
Celgene gained ozanimod in 2015 through its $7.2 billion acquisition of Receptos Inc. (see BioCentury, July 20, 2015).
Celgene added $2.88 to $92.08 on Thursday.