Lilly UC Treatment Holds Edge in Maintenance Study, Setting Up BLA
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Eli Lilly and Company announced Tuesday that mirikizumab, its monoclonal antibody formulation to treat ulcerative colitis (UC), had met the primary endpoint of clinical remission and all key secondary endpoints at one year in a Phase III maintenance study.
LUCENT-2 evaluated the efficacy and safety of mirikizumab in treating patients with moderate-to-severe active ulcerative colitis. All patients in this study were previously enrolled in a 12-week induction study, LUCENT-1, and received an adequate clinical response.
UC is an inflammatory condition of the digestive tract that makes the colon swell up, causing irritation and discomfort. Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of interleukin 23 – a common therapeutic target for most autoimmune diseases. Mirikizumab is being studied for the treatment of immune-mediated diseases including psoriasis, ulcerative colitis and Crohn's disease.
The LUCENT-1 trial met the desired endpoint of clinical remission. This meant that by the end of the 12-week study, inflammation of the colon was successfully controlled or resolved, leading to normalization or near-normalization of symptoms like stool frequency and bleeding.
The same batch of patients was re-randomized to mirikizumab maintenance dosing in LUCENT-2. The trial saw a statistically higher proportion of patients on mirikizumab meeting the primary endpoint of clinical remission at the end of one year compared to patients who were re-randomized to placebo (p<0.001). All key secondary endpoints were also met. A significantly higher number of patients treated with mirikizumab achieved endoscopic and corticosteroid-free remission, absolute resolution, or near-resolution of bowel urgency. Patients receiving the drug also had reduced intestinal inflammation, improved bowel urgency and maintenance of remission.
As this was a maintenance study, the frequency of serious adverse events among patients re-treated with mirikizumab was monitored closely in comparison to the placebo to evaluate if safety levels were consistent with LUCENT-1. The frequency was noted to be numerically lower compared to placebo and the overall safety profile was consistent with not only that of LUCENT-1, but also with several other studies within the anti-IL-23p19 antibody class.
The most common treatment-emergent adverse events reported in the patients re-treated with mirikizumab were nasopharyngitis, arthralgia and exacerbation of ulcerative colitis. Additional adverse events of interest reported included hypersensitivity, injection site reaction, depression, liver enzyme elevation, herpes zoster and oral candidiasis.
“In this maintenance study, treatment with mirikizumab demonstrated clinically meaningful and statistically significant improvements in clinical, endoscopic and histologic measures, including reduction of bowel urgency – a novel endpoint in the LUCENT program,” said Dr. Bruce E. Sands, M.D., M.S., Dr. Burrill B. Crohn Professor of Medicine and chief of the Dr. Henry D. Janowitz division of gastroenterology at the Icahn School of Medicine at Mount Sinai. “Bowel urgency is one of the most bothersome and disruptive symptoms people living with ulcerative colitis experience, and the LUCENT program leveraged an innovative and systematic patient-centric approach to assess patients' symptoms.”
These results set Lilly up well to submit a Biologics License Application (BLA) in the first half of 2022. The company also plans to file for approval with other global regulatory agencies in the same timeframe.
“Existing therapies aren't fully meeting the needs of people with ulcerative colitis who still have unresolved symptoms that impact their health and quality of life," Dr. Lotus Mallbris, M.D., Ph.D., vice president of global immunology development and U.S. and global medical affairs at Lilly said in a statement. “These positive long-term results provide evidence that mirikizumab has the potential to be an effective treatment option and become the first medicine of its kind for people with ulcerative colitis, including those who suffer from bowel urgency.”