Potential cancer-causing side effects of Johnson & Johnson's
In the FDA briefing documents for the advisory committee, the reviewers seemed happy with the data from the two phase 3 trials -- describing them as "adequate and well-controlled" -- but were a little worried about the long-term safety of the drug.
Specifically, ustekinumab blocks interleukin-12 (IL-12) and IL-23, two immune-system proteins that promote inflammation. When the IL-12/IL-23 are blocked or removed in mice, the rodents get cancer at a higher rate. While the patients taking ustekinumab in clinical trials didn't have an increased rate of cancer, the trials probably didn't go on long enough to see an effect.
The agency wants to know if the outside doctors on the committee think it's sufficient to put the animal data warning of the potential cancer danger on the label, or whether an additional safety trial is needed. The latter would obviously cause a lengthy delay in getting ustekinumab on the market, but I don't think they'll go that far.
After all, the current psoriasis drugs that inhibit a different immune-system protein called TNF -- Abbott Labs'
The only other concern that the FDA seems to have with ustekinumab is the dosing regimen that Johnson & Johnson wants to list. Two doses of ustekinumab were tested -- both of which worked -- but analysis revealed that heavier patients responded better to the higher dose. Johnson & Johnson wants the dosing noted on the label, but even if the committee balks, I'm not sure it’s a major problem for the company. Doctors aren't stupid and, given the two dosing options, they'll likely pick the higher one for their larger patients.
While the addition of potential cancer side-effects of ustekinumab to the label probably isn't what Johnson & Johnson would like, but it's akin to being diagnosed with a curable skin cancer and not a late-stage lung cancer. In other words, having the warning added shouldn't be the end of the world for ustekinumab. I expect the committee to give the drug a thumbs-up tomorrow even if they suggest that the FDA adds the warning.