New Biologic Ustekinumab Receives Positive Opinion From European Regulatory Authority For The Treatment Of Moderate To Severe Plaque Psoriasis

Main Category: Dermatology
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 28 Nov 2008 - 2:00 PST

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Janssen-Cilag announced that ustekinumab, the first in a new class of biologics, has received a positive opinion for the treatment of adults with moderate to severe plaque psoriasis from the European Committee for Medical Products for Human Use (CHMP). People living with psoriasis suffer not only from the symptoms of the disease itself, but also have to endure the burden and inconvenience of the treatments used to manage this chronic condition. As psoriasis has the potential to be a visible and disfiguring disease, people living with psoriasis may also become isolated and depressed if the condition is inadequately controlled.1 This positive opinion brings another effective treatment option a step closer for psoriasis patients. The CHMP's positive opinion is now referred for final action to the European Commission.

The CHMP recommended approval of ustekinumab for adults with moderate to severe plaque psoriasis who have failed to respond to, have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA (a light sensitising medication, psoralen, combined with exposure to ultraviolet A light).

This positive opinion is based on data from two large pivotal Phase 3 (PHOENIX 1 & 2), multi-centre, randomised, double blind, placebo controlled trials involving nearly 2,000 adult patients in whom the efficacy and tolerability of ustekinumab in the treatment of moderate to severe psoriasis was evaluated2,3 The primary endpoint of both these pivotal studies was a reduction in psoriasis severity (measured using the Psoriasis Area and Severity Index, PASI) of at least 75% (PASI 75) by week 12. Just over two-thirds of patients achieved this outcome in both studies after two doses at weeks 0 and 4. Ustekinumab therapy was well-tolerated during the trials, with a tolerability profile generally comparable to placebo up to week 12. Both PHOENIX 1 and PHOENIX 2 are currently ongoing and will last five years, with data up to 76 weeks published so far. The benefits of continued maintenance therapy were generally shown to last until at least week 76 in patients receiving ustekinumab every 12 weeks. This was demonstrated using a randomised withdrawal design in the first pivotal study (PHOENIX 1), where patients were randomised to either continue ustekinumab or switch to placebo at week 40 in a double-blind design.1

About Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory disease, which results from the over-production of skin cells resulting in their accumulation on the surface of the skin, which causes red, scaly plaques that may itch and bleed. It is estimated that up to three percent of the world's population has psoriasis.4 Twenty to thirty percent of people with psoriasis have disease that is considered severe.5

About ustekinumab

Ustekinumab is a new, human monoclonal antibody with a novel mechanism of action that targets the p40 sub-unit of cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in regulating immune responses, and that are thought to be associated with some immune-mediated inflammatory disorders, including plaque psoriasis.

Tolerability profile

Rates of serious adverse events, including serious infections, malignancies and cardiovascular events, were low and consistent with the expected background rates. The most common adverse events in Phase 3 clinical trials were arthralgia, cough, headache, injection site erythema, nasopharyngitis and upper respiratory tract infection.

Centocor, Inc. developed ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag has exclusive marketing rights in all countries outside of the United States.

References

1. Dubertret L, Mrowietz U, Ranki A, et al. European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol. 2006;155(4):729-736.

2. 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). The Lancet. 2008;371:1665-74

3. Papp K, 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). The Lancet. 2008;371:1675-84.

4. International Federation of Psoriasis Associations. Profile of Psoriasis. Available at: http://www.ifpa-pso.org/t2.aspx?p=107478 Accessed on 10 November 2008

5. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005. Br J Dermatol. 2005;153(3):486-497.

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