Lilly’s announcement that its psoriasis project ixekizumab outperformed Enbrel in pivotal trials means that all the entrants in the new IL-17 antibody class have now taken their marks on the starting line.
With very little to choose from in terms of efficacy or safety, Lilly’s fight with Novartis’s secukinumab and AstraZeneca and Amgen’s brodalumab will come down to commercial factors like price, marketing power and first-mover advantage, while payers will press to emphasise older, less-expensive drugs first. Novartis has stolen a march on the other two with an FDA approval decision expected early next year, and will need to make the most of a clear field while it has it.
Ixekizumab’s 3,866-patient Uncover programme found that a greater proportion patients with moderate to severe disease taking the antibody achieved a 75% reduction in the psoriasis area and severity score (PASI 75) over 12 weeks than did patients taking Enbrel or a placebo. Of the ixekizumab patients, 78-90% achieved PASI75, and 31-41% achieved PASI100, or full skin clearance, a secondary endpoint.
Lilly did not disclose the comparative PASI75 scores for Enbrel in the head-to-head Uncover 2 and 3 trials, but it did say the PASI100 score was 5-7% for the Amgen TNF-alpha alternative.
Ixekizumab represents the third antibody acting on the interleukin-17 (IL-17) pathway to disrupt disease processes; this pro-inflammatory cytokine drives excess skin cell proliferation and activation. The Lilly project has a high affinity for IL-17A. Novartis’s secukinumab, which passed its phase III test more than a year ago, also targets IL-17A, while AstraZeneca and Amgen’s brodalumab binds to the cellular receptor for IL-17.
|Comparative PASI 75 scores for IL-17 agents in phase III|
|Secukinumab||67% (low dose) 77.1% (high dose)*||4.9% (placebo) 44% (Enbrel)|
|Brodalumab||60.3% (low dose) 83.3% (high dose)||2.7% (placebo)|
|*From Fixture trial with active control; **Lilly disclosed only PASI100 score for Enbrel. Source: Company disclosures|
As befits its position as the first to report data and file for approval, the Novartis project has the biggest forecast attached to it: $899m in 2020, according to EvaluatePharma’s consensus. Brodalumab and ixekizumab come in at $806m and $546m respectively.
Although all are being tested in a number of inflammatory conditions, secukinumab is the only one for which analysts have pencilled in numbers in any other condition, with 17% of 2020 sales expected to come from rheumatoid arthritis.
Secukinumab is due an FDA decision in early 2015, with an advisory committee meeting scheduled for October 20. As Lilly has indicated that it will file ixekizumab in the first half of 2015 and brodalumab likely to be on a similar time frame, Novartis will have about a year to capitalise on the open field.
Where the market is
What will that field be? Psoriasis affects an estimated 125 million people around the world, about 17% of which suffer from moderate to severe disease.
Treatment protocols now call for doctors to try methotrexate, or ultraviolet therapy, for example, first line, with TNF-alpha agents Enbrel or Remicade or the IL-12 and 23 antibody Stelara used second line. The fact Novartis and Lilly put Enbrel squarely in their sights early when designing their phase III programmes is a sign of where they see the competition – although Stelara is also in head-to-head trials against brodalumab and secukinumab.
The trouble is that Enbrel and Remicade are both fairly efficacious; the former helped about half of patients achieve PASI75 and the latter anywhere from 75% to 88%. With Remicade already facing biosimilar competition from Celltrion’s Remsima, and a potential for a US launch between now and 2018, there can be no doubt what payers will prefer.
The remaining products will be playing for the high end of the market, and there does not appear to be a best-in-class option. How the new drugs are priced and marketed will be as much a factor in their success as their clinical performance.