I did a pretty quick read of the documents, focusing on the FDA briefing document of course.
Anyone holding INCY stock, or any company with a drug in the RA space, would do themselves a great service by reading these documents.
Here is my view:
Not a slam dunk as some had suspected.
Efficacy issues
Is radiographic progression well-validated? Five issues in the interpretation of this data are provided on p 17, the biggest being lack of dose-response, small treatment effect and lack of progression in PBO group.
Safety issues
Mechanistic issues in the tox species (will be interesting to compare with INCY/LLY compound. Rats show bacterial infections, histiocytosis, and inflammation. In monkeys, lymphoma and bacterial/viral infections.
In man, increased malignancies, in particular atypical lymphoma such as CNS lymphoma. Deaths were increased in treated patients, though the safety data base needs to be extended time-wise to understand better the overall incidence in patient years and thus risk. Lymphoma was also seen in the transplant setting. Consistent with tofacitinib being an immunosuppressant, increases in viral infections.
Lipids (TGLs, LDL and HDL) were elevated in treated patients by ~15%. Other blood abnormalities were also noted. Not enough CV events were observed to unequivocally determine an effect here, as is usual at this stage.
Could be a close AdComm vote. Meeting will be available via webcast. |
