Stelara (Ustekinumab | Centocor, Inc.) has gained the U.S. Food and Drug Administration (FDA) approval for the treatment of moderate-to-severe plaque psoriasis in adults. Centocor holds the exclusive marketing rights for ustekinumab in the United States.
The approval followed positive results obtained from three studies consisting of 2,266 patients with psoriasis. Both the phase III, parallel, double-blind, placebo-controlled crossover trial (PHOENIX 1), involving 766 patients, and the multicenter, phase III, double-blind, placebo-controlled study, involving 1,230 patients (PHOENIX 2), demonstrated the efficacy of ustekinumab in treating moderate-to-severe psoriasis. Dosing for 12 weeks was reported to be sufficient to maintain efficacy for one year. Patients who failed to respond to this dosage were successfully treated with an intensified regimen of once every 8 weeks.
In November last year, the European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) expressed a positive opinion for use of the monoclonal antibody in the treatment of adult patients with moderate-to-severe plaque psoriasis, failing to respond to other systemic therapies. The drug was later approved in the same year by the Canadian Health Authority for such chronic patients scheduled for treatment with phototherapy and systemic therapy.
Ustekinumab, a novel human monoclonal antibody, acts by targeting the cytokines interleukin-12 (IL-12) and IL-23, which play an important role in immune responses and inflammatory diseases. With regard to the mode of action in psoriasis, the drug mimics the action of endogenous monoclonal antibodies and blocks the effects of these proteins which are responsible for overproduction of skin cells and inflammation in the condition. An increased risk of infection and cancer are the potential adverse effects of ustekinumab.
According to the National Institute of Health (NIH), 7.5 million Americans are affected by psoriasis. A chronic multisystem disorder, psoriasis is associated with several trigger factors such as stress, smoking, alcohol, and medications, including antimalarials, lithium and beta-blockers. However, the definite etiopathogenesis has not yet been clearly elucidated. The plaque type of psoriasis is seen in around 80% of the patients, and is characterized by raised, erythematous lesions with silvery scales on the knees, scalp, elbow, and back. Topical treatment with coal tar, corticosteroids and retinoids, phototherapy, and photochemotherapy are the mainstay in milder forms of the disease, while systemic therapy with retinoids and immunosuppressants are useful in resistant psoriasis. With the current approval, patients are provided with the option of a biologic drug, such as ustekinumab, for the treatment of more severe cases of the disease.
About Centocor: Headquartered in Horsham, Pennsylvania, the biomedical company is a wholly-owned subsidiary of Johnson & Johnson. Pioneering in the development of products related to cancer and immunology, Centocor also works on treatment for Crohn’s disease, rheumatoid arthritis and plaque psoriasis. Remicade® (infliximab), a monoclonal antibody to treat autoimmune diseases, is one of their most successful products to date.
References
1. FDA Approves New Drug to Treat Psoriasis. Press Release. FDA. Last accessed October 01, 2009.
2. FDA issues complete response letter to Centocor for ustekinumab biologic license application. Press Release. Centocor. Last accessed October 01, 2009.
3. Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008 May 17;371(9625):1665-74.
4. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008 May 17;371(9625):1675-84.
