Immunology and Biotherapies

Abstract

 

Psoriasis is a chronic inflammatory skin disorder that affects approximately 2–3% of the population worldwide and has severe effects on patients’ physical and psychological well-being1, 2, 3. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg−1 groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg−1 group and 13 out of 14 subjects in the 10 mg kg−1 group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.

Via Krishan Maggon

Abstract

 

Psoriasis is a chronic inflammatory skin disorder that affects approximately 2–3% of the population worldwide and has severe effects on patients’ physical and psychological well-being1, 2, 3. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg−1 groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg−1 group and 13 out of 14 subjects in the 10 mg kg−1 group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.

Via Krishan Maggon

Targeting pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) has been an effective therapeutic approach in patients with a variety of autoimmune diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis. New targets along the interleukin-17 (IL-17)–TH17 (T helper cell 17) pathway, 

Via Krishan Maggon

Selective targeting of the IL23 pathway: Generation and characterization of a novel high-affinity humanized anti-IL23A antibody. . .

Via Krishan Maggon

Basel, 19 January 2015 - Novartis announced today that the European Commission (EC) has approved Cosentyx(TM) (secukinumab, formerly known as AIN457) as a first-line systemic* treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy.

 

Cosentyx (at a dose of 300 mg) is the first and only interleukin-17A (IL-17A) inhibitor to be approved in Europe and this approval marks a significant milestone in the treatment of psoriasis, providing a new and important first-line biologic treatment option for patients. Currently, all biologic treatments for psoriasis, including anti-tumor necrosis factor therapies (anti-TNFs) and Stelara®** (ustekinumab) are recommended for second-line systemic therapy in Europe[2-4].

 

The EU approval follows the recent results of the Phase IIIb CLEAR study, which showed that Cosentyx was superior to Stelara®** in clearing skin of patients living with moderate-to-severe plaque psoriasis. The CLEAR study was the second head-to-head study for Cosentyx. Cosentyx also showed superiority to Enbrel®*** (etanercept) in clearing skin in the FIXTURE study[6]. In the Phase III clinical program the overall safety profile of Cosentyx was favorable, with minimal differences seen between etanercept and ustekinumab in head-to-head comparison[5,6].

 

In addition to the EU, Cosentyx has been approved in Australia for the treatment of moderate-to-severe plaque psoriasis and in Japan for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA).

 

The US Food and Drug Administration (FDA) decision in moderate-to-severe plaque psoriasis is anticipated early in 2015 following the unanimous recommendation of approval in October 2014 from the Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) to the US FDA.

Via Krishan Maggon