LONDON — Phase three trials of the selective interleukin (IL)-23 blocker risankizumab are replicating the promising results achieved by phase two trials, investigator Andrew Blauvelt of the Oregon Medical Research Center in Portland, Ore., reported at the Psoriasis: From Gene to Clinic International Congress, in London on Saturday.
He presented the first results from the IMMhance trial, one of four phase three trials being conducted on risankizumab by drug companies AbbVie and Boehringer Ingelheim.
Risankizumab is a potent humanized IgG1 monoclonal antibody that inhibits IL-23 by speciï¬cally binding its p19 subunit. In a phase two trial, the efï¬cacy and safety of risankizumab for treating moderate-to-severe plaque psoriasis was found to be superior to that of the IL-12/IL-23 inhibitor ustekinumab at 12 weeks; PASI 90 was achieved in 77% patients treated with risankizumab compared with 40% of those treated with ustekinumab.
In the phase three trial IMMhance 507 patients were randomized 4:1 to receive either risankizumab (150 mg at weeks 0 and 4) or placebo and the percentages of patients achieving PASI 90 and static Physician’s Global Assessment 0 or 1 were assessed at week 16.
The results showed that 73.2% of patients on risankizumab achieved a PASI 90 compared with 2% on placebo and 83.5% of patients on risankizumab reached an sPGA of 0-1 (p<0.001). Complete clearing of the disease was seen in almost half of patients with the secondary endpoints of PASI 100 and sPGA 0 being achieved by 47.2% and 46% of patients respectively. Two third of patients (65.4%) reported that psoriasis had a negligible impact on their quality of life at 16 weeks (Dermatology Life Quality Index 0-1).
Dr. Blauvelt said: “Risankizumab was superior to placebo in the treatment of adult patients with moderate to severe plaque psoriasis, as demonstrated by the co-primary endpoints as well as all the ranked secondary endpoints at week 16. The safety profile was consistent with what we have seen both with risankizumab and with other IL-23 blockers and there were no new or unexpected safety findings.”
Reported serious and severe adverse events were lower in patients receiving active treatment than in the placebo group. “This is a good sign,” he acknowledged, but adding: “We really need to assess biologic safety [vs] the placebo group over many years.”
Early results from the other three phase 3 trials have also been recently revealed. In these trials risankizumab was compared to compared to ustekinumab and adalimumab and achieved significantly greater response of clear or almost clear skin (sPGA 0/1) with rates ranging from 84 to 88% at week 16.
Dr. Blauvelt said that the sPGA achieved in the IMMhance trial was the lowest of the four, perhaps because of the high exposure among patients to previous biologic therapies previously.
More than 50% of patients had been exposed to biologics with 36.5% having received prior TNF inhibitor therapy in in IMMhance. Patients had a mean age of 49.2 years, mean weight was 92.0 kg and 70.2% were male. Patients’ mean baseline PASI and body surface area were 20.1 and 26.1% respectively and 34.5% had diagnosed or suspected psoriatic arthritis. Randomization in IMMhance. was stratiï¬ed by weight and prior TNF inhibitor exposure.
The ultimate aim of the two-year long IMMhance trial is to look at how long the effects of risankizumab last because long continued responses to risankizumab were seen in the phase 2 trial after patients came off the drug. As a result, the initial 16-week treatment period is being followed by randomised withdrawal and subsequent retreatment with risankizumab.
A. Blauvelt, K.A. Papp, M. Gooderham, et al. “Efï¬cacy and safety of risankizumab, an interleukin-23 inhibitor in patients with moderate-to-severe chronic plaque psoriasis: 16-week results from the phase III IMMhance trial,” Psoriasis: From Gene to Clinic International Congress, London, 2nd December 2017, 11.15. http://psoriasisg2c.com/wp-content/uploads/2017/11/Online-Psoriasis-G2C-... (page 69).