Risankizumab Outperforms Humira, Stelara in Treating Plaque Psoriasis

As AbbVie’s best-selling Humira faces oncoming biosimilar competition, the drug maker is developing a new innovator product that could help it retain a hold on the market; new results from 3 recent phase 3 clinical trials show AbbVie’s investigational interleukin-23 (IL-23) inhibitor, risankizumab, to be more effective than adalimumab (Humira) or ustekinumab (Stelara) in patients with moderate-to-severe plaque psoriasis.

All 3 trials met the co-primary endpoints of at least a 90% improvement in symptoms in the Psoriasis Area and Severity Index (PASI 90), and a score of clear or almost clear as measured by the static Physician Global Assessment (sPGA) scale at week 16, compared with placebo or adalimumab.

“What is particularly exciting is the number of patients who achieved high rates of skin clearance in these 3 head-to-head clinical trials,” said Michael Severino, MD, AbbVie’s executive vice president of research and development and chief scientific officer. “Risankizumab has the potential to provide a meaningful new treatment option for people living with psoriasis.”

Two of the trials reported [ultIMMA-1 (n = 506) and ultIMMa-2 (n= 491)] were replicate phase 3 trials evaluating the safety and efficacy of risankizumab (150 mg) compared with placebo or ustekinumab (45 mg or 90 mg based on patient weight). The third trial, IMMvent, studied risankizumab versus adalimumab (n = 605).

AbbVie notes that phase 3 trials of risankizumab in psoriasis are ongoing, and the drug is also being investigated to treat Crohn’s disease and psoriatic arthritis. Future trials are planned to investigate risankizumab in ulcerative colitis.

Risankizumab Versus Placebo or Ustekinumab (ultIMMA-1 and ultIMMa-2)

After 16 weeks of treatment, 75% of patients receiving risankizumab in both studies achieved a response of PASO 90, compared with 5% of patients receiving placebo in ultIMMa-1 and 2% receiving placebo in ultIMMa-2. These response rates were significantly greater than the ustekinumab PASI 90 response rates of 42% (ultIMMa-1) and 48% (ultIMMa-2). Additionally:

• A sPGA score of clear or almost clear (sPGA 0/1) was achieved by 88% and 84% of patients receiving risankizumab in ultIMMa-1 and ultIMMa-2 at week 16, respectively, compared with 8% and 5% of patients receiving the placebo
• The response rates to risankizumab were also significantly greater than the ustekinumab sPGA 0/1 response rates of 63% (ultIMMa-1) and 62% (ultIMMa-2)
• At week 16 and 1 year, twice as many patients treated with risankizumab achieved complete skin clearance (PASI 100), compared with patients treated with ustekinumab
• At week 16, 36% and 51% of patients receiving risankizumab achieved PASI 100 in ultIMMa-1 and ultIMMa-2, respectively, compared with 12% and 24% of patients receiving ustekinumab
• At 1 year, 56% and 60% of patients receiving risankizumab achieved PASI 100 in ultIMMA-1 and ultIMMa-2, respectively, compared with 21% and 30% of patients receiving ustekinumab
• PASI 90 was achieved by 82% and 81% of risankizumab patients in ultIMMa-1 and ultIMMa-2 at 1 year, respectively, compared with 44% and 51% of ustekinumab patients

Risankizumab Versus Adalimumab (IMMvent)

IMMvent data showed that patients receiving risankizumab had significantly higher response rates than those receiving adalimumab:

• At week 16, 72% of patients receiving risankizumab (150 mg) achieved PASI 90, compared with 47% of patients treated with adalimumab (80 mg initially followed by 40 mg every 2 weeks starting 1 week after initial dose)
• At week 16, an sPGA score of 0 or 1 was achieved by 84% of patients receiving risankizumab, compared with 23% of patients treated with adalimumab

In the second phase of IMMvent (week 16 to 44), patients with a response to adalimumab of PASI 50 to less than PASI 90 at week 16 were re-randomized to either switch to risankizumab or continue adalimumab. Of these patients:

• 66% achieved PASI 90 at week 44 when switched to risankizumab, compared with 21% of patients who stayed on adalimumab
• 40% of patients who switched to risankizumab achieved a PASI 100 at week 44, compared with 7% of patients who stayed on adalimumab

“In this trial, 4 out of 5 patients achieved clear or almost clear skin with risankizumab at week 16,” noted Kristian Reich, MD, the principal investigator for IMMvent. He said the results support previous findings that risankizumab has the potential to address unmet needs for patients with psoriasis.

No new safety signals were detected across the phase 3 program for plaque psoriasis. In ultIMMa-1 and ultIMMa-2, serious adverse events through week 16 occurred in 2% of patients on risankizumab in both studies, compared with 3% and 1% of patients on placebo and 8% and 3% of patients on ustekinumab, respectively.

Through 1 year, SAEs in the ultIMMa-1 and ultIMMa-2 trials occurred in 8% and 7% of patients in the continuous risankizumab group, respectively, compared with 11% and 7% of patients treated continuously with ustekinumab. One patient in ultIMMa-2 receiving risankizumab died from a sudden cardiac arrest 101 days after the last dose of study drug; a second patient receiving risankizumab died 161 days after the last dose (cause of death is unknown). Both patients had a history of cardiovascular risk factors. There were no deaths reported among patients in ultIMMa-1.