In a tough indication and a space crowded with developers, Eli Lilly and Co.’s phase III study of the monoclonal antibody mirikizumab for treating moderate to severe ulcerative colitis made a mark by meeting its primary endpoint of clinical remission and all key secondary endpoints compared to placebo.
Primary endpoint of the 12-week Lucent-1 maintenance study of the anti-IL-23p19 therapy was clinical remission at week 12 compared to placebo (p<0.0001). Clinical remission, Lilly noted, is when colon inflammation is controlled or resolved, leading to normalization or near-normalization of symptoms such as stool frequency and bleeding.
The trial’s key secondary endpoints comparing mirikizumab to placebo at week 12 resulted in highly statistically significant “p” values, including reduced bowel urgency, clinical response, endoscopic remission, symptomatic remission and improvement in endoscopic histologic inflammation.
Mirikizumab, a humanized IgG4 monoclonal antibody that binds to the p19 subunit of interleukin-23 that is also being studied for treating immune diseases including psoriasis and Crohn's disease, also showed improvement in patient symptoms as early as four weeks after initiating treatment. It also reduced symptoms for those who had previously not responded to or stopped responding to biologic and/or JAK inhibitor therapies.
The Lucent phase III program also includes Lucent-2 and Lucent-3. The multicenter, randomized, double-blind, placebo-controlled Lucent-2 study is ongoing and consists of patients who completed Lucent-1.
The news saw the Indianapolis-based Lilly stock (NASDAQ:LLY) stabilize after a precipitous 9.4% drop from March 12’s $208.08 per share to March 15’s $189.16 closing, which followed presentation of positive phase II Trailblazer-Alz results at the International Conference on Alzheimer's and Parkinson Diseases over the weekend.
The ulcerative colitis market is large with an average annual growth rate of about 3% in the U.S. and western Europe, according to DRG. The growth drivers include the continued uptake of existing targeted therapies, including TNF-α inhibitors, a CAM inhibitor (Entyvio, Takeda Pharmaceutical Co. Ltd.), a Jak inhibitor (Xeljanz/Xeljanz XR, Pfizer Inc.) and an IL-12 / IL-23 inhibitor (Stelara, Johnson & Johnson). Emerging therapies will have a significant impact on the market, DRG added, providing more options for patients.
Mirikizumab is one of the IL-23 inhibitor therapies that could impact the market, according to DRG, along with Abbvie Inc.’s Skyrizi (risankizumab) and Tremfya (guselkumab) from the Janssen Pharmaceutical Co. of Johnson and Johnson.
Skyrizi is in a phase III study in Crohn’s disease and, in January, data from adults with moderate to severe disease showed both doses (600 mg and 1,200 mg) met the co-primary endpoints of clinical remission measured by CDAI and endoscopic response, both at week 12 (p<0.001 for both doses on both endpoints).
In October, Janssen posted interim results of its phase II study of Tremfya (guselkumab) vs. placebo for treating moderately to severely active Crohn’s disease. At the 12-week mark, Tremfya induced significantly greater improvements compared to placebo across key clinical and endoscopic outcome measures, with a safety profile consistent with approved indications.
There’s also Bristol Myers Squibb Co.’s sNDA, using a priority review voucher, for ozanimod (Zeposia) to treat moderate to severe ulcerative colitis. The application has a May 30 PDUFA date. As a result, according to DRG, the launch date for ozanimod in the U.S. has shifted from late 2022 to mid-2021.
“Ozanimod will now enjoy one extra year on the UC market during our forecast period than previously expected,” DRG added.
Regarding the Lilly stock’s deep dip, on March 15 Mizuho analyst Vamil Divan wrote that while the data were solid, they were below the high expectations of investors. Divan added that the phase II numbers were cause for optimism, with possible commercialization in 2024.
“Beyond donanemab, we see multiple potential upside drivers to the Lilly story, including diversified near-term top-line growth, continued margin expansion, and a promising pipeline, with limited patent loss exposure,” Divan wrote.