A phase 3 clinical trial of mirikizumab in ulcerative colitis has met its primary endpoint, boosting Eli Lilly’s hopes of establishing the anti-IL-23p19 antibody in gastrointestinal disorders.
Lilly has ceded a head start to AbbVie’s anti-IL-23 antibody Skyrizi and Johnson & Johnson’s Stelara, which hits IL-12 and IL-23, in plaque psoriasis. Faced with a competitive market, which also features Novartis’ IL-17 drug Cosentyx, Lilly embarked on a broad R&D program that positioned it to establish mirikizumab as a late entrant to the psoriasis space and an early mover in gastrointestinal disorders.
The top-line phase 3 results provide partial validation of Lilly’s big bet on mirikizumab. In LUCENT 1, Lilly set out to compare intravenous mirikizumab to placebo in patients with moderately to severely active ulcerative colitis who had been failed by conventional or biologic therapies.
After 12 weeks, the rate of clinical remission was significantly higher in the mirikizumab arm, causing the trial to hit its primary endpoint with a p-value of less than 0.0001. Subjects were classed as being in clinical remission when the control or resolution of colon inflammation led to the normalization, or near-normalization, of symptoms such as stool frequency and bleeding.
Mirikizumab also beat placebo against all key secondary endpoints including bowel urgency and endoscopic remission “with highly statistically significant p-values,” Lilly said. Symptoms stopped as early as four weeks after treatment. The responders to mirikizumab included patients failed by JAK inhibitors and biologic therapies.
The top-line readout suggests mirikizumab improves outcomes in ulcerative colitis patients who have exhausted existing treatment options. However, the lack of numbers in the Lilly release make it hard to gauge how big an impact mirikizumab could have on the market.
Lilly plans to disclose the full data in the future but for now is still working to gather evidence on the effects of mirikizumab in ulcerative colitis. A placebo-controlled maintenance study of mirikizumab in patients who have completed the 12-week LUCENT-1 induction is ongoing, as is a long-term efficacy and safety trial. The trials will give Lilly 52-week data on the effects of mirikizumab.
Full results from the studies are expected early next year. The timeline gives Lilly a shot at getting mirikizumab to market in ulcerative colitis before developers of other anti-IL-23 antibodies. AbbVie is running a phase 2/3 trial of Skyrizi in ulcerative colitis but last year delayed the estimated primary completion. ClinicalTrials.gov lists the new primary completion as September 2022. J&J’s IL-23 drug Tremfya is in a phase 2/3 ulcerative colitis trial with a primary completion date of June 2022.
Stelara is cleared for use in ulcerative colitis but appears to be less effective than pure IL-23 inhibitors in psoriasis. If Lilly shows pure IL-23 inhibitors have a similar edge over Stelara in ulcerative colitis, it could carve out a piece of the market before facing competition from Skyrizi and Tremfya.