A head-to-head study against the market leader is a risky strategy, but one that has paid off for Amgen and AstraZeneca. The companies’ IL-17 receptor blocker brodalumab has beaten Johnson & Johnson’s anti-IL12/23 MAb Stelara in a phase III plaque psoriasis trial, potentially setting it up to take a decent slice of a crowded market.
One of the primary endpoints of the Amagine-3 trial was the proportion of patients whose disease was entirely resolved, where the project hit significance. Even on the more common 75% clearance threshold brodalumab stacks up well against the other IL-17 pathway inhibitors. Forecast blockbuster psoriasis sales by 2020, which hitherto seemed somewhat optimistic, now look quite reasonable.
The trial enrolled 1,800 patients with moderate to severe plaque psoriasis who were treated with 140mg or 210mg doses of brodalumab every two weeks, an undisclosed dose of Stelara, or placebo. In the brodalumab versus Stelara arm the primary endpoint was met, with a significantly higher proportion of brodalumab patients achieving total clearance of skin disease at 12 weeks as measured by the psoriasis area severity index (PASI 100) compared with patients treated with Stelara.
In another trial arm a significantly higher proportion of brodalumab-treated patients had at least a 75% improvement in disease severity from baseline as measured by PASI 75 compared with placebo. However, at the lower 140mg brodalumab dose there was less of a spread between the two agents on this measure.
|Results of phase III Amagine-3 trial|
|Proportion of patients meeting PASI 100||Proportion of patients meeting PASI 75|
Serious side-effects were more common with brodalumab than Stelara, with 1.6% of brodalumab-treated patients having severe adverse events compared with 0.6% in the Stelara arm and 1% in the placebo group. The companies did not state the significance of this.
The PASI 75 scores of the 210mg dose are comparable with the two main rival IL-17 inhibitors, Novartis’s secukinumab and Lilly’s ixekizumab (Lines drawn for coming IL-17 psoriasis fight, August 22, 2014). Both are further advanced: regulatory submissions for ixekizumab are planned for the first half of 2015, and secukinumab is already under review in the EU and US. Amgen and Astra have not yet said when they plan to file brodalumab.
High growth rates
Stelara, often referred to as the standard of care although it is in fact used second line after methotrexate or ultraviolet therapy, was launched in 2009, and in 2013 sold $1.5bn in psoriasis globally. Sales are forecast to grow at 13% annually until 2020, according to EvaluatePharma’s consensus data.
Consensus forecasts for brodalumab put launch at 2015, with psoriasis sales of just over $1bn by 2020. Estimates could well rise on the back of these results, although consensus for sales in 2020 has already doubled since the beginning of the year. UBS analysts predict peak sales of $1.3bn by 2022.
Amagine-2, another phase III study pitting brodalumab against Stelara, is due to read out by the year-end, as is a Novartis-run trial that tests secukinumab versus Stelara. After these report it will be easier to see whether brodalumab really could merit the best-in-class tag.
|Amagine-1||Broda vs Stelara, 660 patients||NCT01708590|
|Amagine-2||Broda vs Stelara, 1,800 patients||NCT01708603|
|Amagine-3||Broda vs Stelara, 1,800 patients||NCT01708629|
|Clear||Novartis's secukinumab vs Stelara, 640 patients||NCT02074982|