FDA Says J&J Psoriasis Drug Could Increase Cancer Risk
By John Wolper
09:06, June 14th 2008
The FDA reviwers noted in a analysis released on Friday that the experimental psoriasis drug, ustekinumab, created by J&J is effective to treat the symptoms, but it could increase the risk of cancer.
Ustekinumab is a first in class, new molecular entity proposed for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
This biologic product is a fully human IgG1 antibody directed against the p40 subunit of the IL-12 and IL-23 cytokines. The IL-12 and IL-23 cytokines are comprised of a shared p40 subunit and a subunit unique to each cytokine, p35 for IL-12 and p19 for IL-23. The contribution of IL-12 and IL-23 to the psoriatic process is still being elucidated.
In its advisory, FDA noted that literature data indicates that inhibition of IL-12/IL-23 expression leads to an increased carcinogenic risk: systemic administration of IL-12 exhibits an anti-tumor effect in mice, inhibition of IL-12/IL-23 expression with a murine monoclonal antibody enhances tumor formation in mice challenged with squamous cell carcinoma cells and removal of the IL-12/IL-23 gene in knockout mice enhanced tumor formation in mice.
There is sufficient nonclinical data in the literature indicating an increased carcinogenic risk with inhibition of IL-12/IL-23 expression to justify inclusion in labeling of this animal data to inform prescribers about the potential carcinogenic risk from ustekinumab use, FDA added.
Ustekinumab is believed to interrupt signaling and cytokine cascades that are central to psoriasis pathology. Since psoriasis is a chronic disease, psoriasis patients may be under treatment for long periods of time.
Long term use of ustekinumab may lead to increased risk of tumor development in psoriasis patients, particularly in those who have been exposed to other therapies which could increase the risk of tumor development, such as UVB, photodynamic therapy, and other immunosuppressive agents, FDA's analysis noted.
A spokesperson for J&J's Centocor, the unit that has developed the drug, said that the risk of cancer is theoretical.
The trials conducted so far by the company have shown the efficacy of subcutaneous injections of ustekinumab 45 mg and 90 mg in the treatment of chronic plaque psoriasis.
The FDA decision to whether approve the drug or not is expected in September. |
