The first look at detailed phase II data on Johnson & Johnson’s new psoriasis agent guselkumab paints a picture of another promising agent in what is a healthy development pipeline for this disease (see tables).
Like the majority of the closely watched new molecules in development for the inflammatory condition, guselkumab targets a cytokine on a pathway thought to be heavily implicated in disease progression, IL-23. With strong efficacy and what seem to be manageable side-effect profiles, many these agents could offer an improvement on the widely used anti-TNFs. However, safety remains a key focus, and is likely to define the real shape of this market in the future.
Presenting data at the American Academy of Dermatology (AAD) meeting this week, J&J said the 293-patient phase IIb study found that a significantly higher proportion of people receiving guselkumab registered improvements in their disease than those given a placebo drug, or Humira, at week 16.
Fewer serious adverse events were reported in the experimental arm than in the Humira arm – 3% vs 5% – and no opportunistic infections were seen with the J&J drug; these are a big risk with the anti-TNFs like Humira.
However, there were three major adverse heart events in guselkumab-treated patients. All patients had existing cardiovascular risk factors, but this signal will be closely watched in future trials.
Concerns about a link to cardiovascular problems are assumed to have de-railed Abbott’s work on briakinumab several years ago. The drugs are different – briakinumab targeted two cytokines - IL-23 and IL-12 while guselkumab only hits IL-23 – but the wide range of options already on the market and in the development pipeline mean that any new agent would be severely handicapped in the market by safety concerns.
J&J has yet to decide which dose to push forward into phase III for guselkumab. But with Stelara growing strongly and Remicade set to remain a strong product in the anti-TNF class, it is clear that J&J is set to remain a dominant player in this market.
|Pipeline of targeted psoriasis agents|
|Status||Project||Company||Pharma class||2018e sales ($m)|
|Filed||Secukinumab (AIN457)||Novartis||IL-17 MAb||497|
|Phase III||Ixekizumab||Eli Lilly||IL-17A MAb||295|
|Tildrakizumab||Merck & Co||IL-23 MAb||77|
|KHK4827||Kyowa Hakko Kirin||IL-17 MAb||11|
|Phase II||Tregalizumab (BT-061)||AbbVie||Anti-CD4/CD25 MAb||3|
Also presenting data at AAD was Novartis, which hopes to become a player with its IL-17a inhibitor secukinumab. The project was filed with European and US regulators last October, and the Swiss pharma giant has conducted a huge clinical programme with the drug, including head-to-head studies with established brands (Novartis psoriasis drug success a positive signal for IL-17 class, July 8, 2013).
This week it presented data from trials using pre-filled syringes and auto-injectors; both succeeded in showing significantly better plaque clearance than placebo. It also unveiled the start of a phase IIIb head-to-head study that will pit secukinumab against Stelara. The Clear trial will seek to recruit 640 patients and use the symptom severity scale PASI90 as its primary endpoint, at 16 weeks.
Secukinumab does have a very quick onset of action, so Novartis is obviously hoping this quality will stand its candidate in good stead when and if it reaches the market. Assuming regulators give the drug the nod, secukinumab would be the first IL-17 targeting therapy to make it that far.
However, the table above shows that there are several other candidates following behind, from other big pharma names that will be equally as determined to take a share of the market. Both Eli Lilly and Amgen, which has partnered with AstraZeneca on brodalumab, should report results from their clinical programmes this year.
These data will shed more light on how this market is likely to develop, in terms of the competitive profile of these agents. Time to onset of action and the longevity of response will remain closely in focus, as will safety.
At this stage these agents hold the potential to threaten the anti-TNFs, but despite their drawbacks products like Humira and Remicade are very well understood, and could become considerably cheaper if biosimilars ever take hold. Which means these agents will have to offer an awful lot more if they are to become the commercial success stories of their predecessors.
|Novel, targeted psoriasis agents already on the market|
|Global psoriasis sales ($m)||Total sales ($m)|
|Stelara||Johnson & Johnson||IL-12 & IL-23 MAb||1,826||2,405||2,888||3,010|
|Remicade||J&J/Merck & Co||Anti-TNFa MAb||1,808||2,236||2,229||7,908|
|Total market excl. generics||9,437||11,603||13,157||43,186|
*Currently only approved in psoriatic arthritis; approval in psoriasis expected in September.
All data sourced to EvaluatePharma.