Eli Lilly’s quest to get mirikizumab across the finish line has not been easy due to COVID-19 interruptions, the war in Ukraine and continued lockdowns in China.
But the Big Pharma is on the other side, at least for one indication. The company is out today with data that the anti-IL-23 antibody helped ulcerative colitis (UC) patients achieve clinical remission. The results come from the phase 3 maintenance trail called LUCENT-2 and were detailed at Digestive Disease Week.
Mirikizumab beat placebo on several clinical, symptomatic and endoscopic endpoints regardless of whether patients had previously failed on TNF inhibitors such as Pfizer’s Xeljanz, Lilly’s Lotus Mallbris, M.D., Ph.D., vice president of global immunology development and medical affairs, said in an interview.
Patients, who had moderately to severely active disease and had failed on other treatments, completed a 12-week induction study, which was called LUCENT-1. In the next study, LUCENT-2, half of the patients who had responded to mirikizumab at 12 weeks went on to achieve remission at the one-year mark, compared to one-fourth in the placebo arm.
Of the patients who achieved remission as of the 12-week mark, nearly two-thirds maintained remission at the one-year mark, compared to one-third of patients in the placebo arm.
Nearly all the patients—or 97.8%—who achieved remission were not taking corticosteroids in the three months or more prior to the end of maintenance therapy, which was given for 40 weeks after the initial induction period. Corticosteroids are a standard of care and are used to quickly control the disease, especially in severe patients. But they come with side effects, and doctors typically aim to avoid long-term use. Many companies look at reducing steroid use as an endpoint in UC, but Mallbris believes Lilly’s results are near the top.
“I can say that the 97% it's, if not the highest, is among the highest, numbers that I have ever seen being achieved, and it's something that will be important for the patients and for doctors,” Mallbris said.
Lilly is also reporting a reduction in bowel urgency, which is a patient-reported outcome. Mallbris said the company has done some studies to determine what outcomes in UC clinical trials are most important to patients. When Lilly detailed the findings of a study in a poster presentation showing that patients found bowel urgency to be one of the most important symptoms of their disease, doctors at a recent medical meeting were shocked.
“I was at a poster, and many doctors came to me personally and they said that this was an eye opener for them,” she said.
Most “heartbreaking” for Mallbris was how much this symptom impacted quality of life for patients, who reported avoiding sexual activity and other things.
Lilly has already filed mirikizumab in the U.S. and the EU in UC. The company is also studying the therapy in Crohn’s disease, with a phase 3 readout due there in 2023. The therapy is part of Lilly's broader push into immunology.
With a strong phase 3 readout and more to come in the next year for mirikizumab, it might be tempting to think that the therapy has blazed through the clinic. But that’s not the case. Back in March 2020, Lilly announced that the program was being put on hold due to the COVID-19 pandemic.
Mallbris said the decision was made to halt treating new patients but to continue with those who had already been participating in the trial. That was a challenge, as the company and site investigators had to carefully consider whether they could continue with in-person endoscopy procedures to assess patients, how patients would get their medicine if they continue at home and so on.
The story reflects one that played out across pharma over the pandemic and one that Lilly will not soon forget. The company mobilized to ensure patients could get their meds and that doctors had the support they needed. Of course, the end result is that Lilly is now able to display the results today, but there were also some key lessons learned for how to run a more patient-focused trial in the future. Lilly has now incorporated more remote or virtual patient visits and brought the lab to the patient, rather than making them travel to visit a specific doctor all the time.
This had the welcome effect of boosting diversity and minority involvement in Lilly’s clinical trials, Mallbris said. Lilly has now taken extra steps to ensure more site investigators of color are trained and that study populations better mimic the disease burden in the wider population.
While this is all great, Mallbris is careful to note that the challenges are not over yet. Clinical trials for mirikizumab in its other indications are still being conducted in Ukraine, which is fighting a brutal war after being invaded by Russia in February, and in China, where a rise in COVID-19 cases has triggered strict lockdowns. Keeping patients in these situations has been difficult, even as they start to feel better and want to continue in the trial.
“While we are proud of what we have achieved for COVID, we should not neglect that challenges still are ongoing,” Mallbris said. “So our program in inflammatory bowel disease has not been without challenges; from COVID, and now … war in Ukraine and yet another shutdown for China.”