Eli Lilly Unveils Long-Term Data for Mirikizumab in Ulcerative Colitis and Crohn’s Disease, Challenging J&J and AbbVie

On October 28, 2024, Eli Lilly announced its IL-23 inhibitor Omvoh（mirikizumab）In Ulcerative Colitis（UC）and Crohn's disease（CD）Long-term efficacy data from Phase III studies. Among them, LUCENT-3 is a Phase III study for moderate to severe active UC, and VIVID-2 is a Phase III study for moderate to severe active CD. The results showed that mirikizumab demonstrated long-term stable efficacy in both inflammatory bowel diseases, with a good safety profile.

Based on the data released this time, Eli Lilly emphasized that mirikizumab is the first and only IL23p19 inhibitor to report long-term, multi-year, sustained efficacy and safety data for UC and CD.

On the same day that Eli Lilly announced its data, Johnson & Johnson also announced its drug TREMFYA targeting the same point.(Guselkumab, Guselkumab Injection)Phase III Study Results in Moderate to Severe Adult Active CD. The Johnson & Johnson press release emphasized that Guselkumab is the first and only IL-23 inhibitor to demonstrate robust results in both induction and maintenance therapy for CD through complete subcutaneous administration.

Notably, there are currently only four IL-23 inhibitors approved and marketed globally, including Guselkumab.(Johnson & Johnson)、Tiragolumab(Kangzhe, Almirall SA, Sun Pharmaceutical Industries Ltd., etc.), Risankizumab(AbbVie)And Mirikizumab(Eli Lilly). Among them, onlyRisankizumab Approved for CD Indication.

Lilly: Mirikizumab

Mirikizumab was first approved by the FDA in October 2023 for the treatment of moderate to severe active ulcerative colitis (UC) in adults, marking Eli Lilly's first drug approved for UC treatment. Currently, the Crohn’s disease (CD) indication for this drug has not yet been approved by the FDA. Further information reveals that mirikizumab was previously designated as a breakthrough therapy by the CDE and is under development for treating adult patients with moderate to severe active CD. Its marketing application was officially accepted by the CDE in October 2024.

The long-term results of the two Phase III studies published this time are as follows:

• LUCENT-3 Study:

LUCENT-3 is the long-term extension study of LUCENT-1 and LUCENT-2, designed to evaluate the three-year efficacy and safety of Mirikizumab in patients with UC. It is reported that both the induction-phase LUCENT-1 and maintenance-phase LUCENT-2 studies included patients who had an inadequate response, no response, or intolerance to treatments such as corticosteroids, immunomodulators, biologics/JAK inhibitors. Among them, in the LUCENT-1 study, 41% of patients were refractory to at least one biologic agent, 3% were refractory to JAK inhibitors, while 57% of patients had not previously received treatment with biologics or JAK inhibitors.

Based on the results obtained over the three-year treatment period, the following points about mirikizumab in the long-term treatment of UC are worth noting:

1. 81% of patients maintained long-term clinical remission.(Patients' symptoms significantly reduced or even disappeared, and their quality of life improved.)；
2. 82% of patients achieved long-term endoscopic remission(Persistent relief or complete disappearance of intestinal inflammation)；
3. 72% of patients achieved mucosal healing;
4. 79% of patients achieved clinical remission without corticosteroids;

5. The patient's bowel urgency symptom score continued to show significant improvement.

• VIVID-2 Study:

The VIVID-2 study is a long-term extension of the Phase III VIVID-1 study and the Phase II SERENITY study, designed to evaluate the 5-year safety and efficacy of mirikizumab in CD patients. Extension data from the VIVID-2 study showed that patients with moderately to severely active CD who received mirikizumab maintained high rates of clinical and endoscopic remission. Based on three additional years of treatment.(Totaling up to 5 years)The following results were obtained from the analysis of subsequent observed cases:

1. 96% of patients through the Crohn's Disease Activity Index（CDAI）Measurement with Clinical Response(A decrease of at least 100 points in the CDAI score)；
2. According to CDAI measurements, 87% of patients are in clinical remission.(Symptoms significantly improved or disappeared)；
3. 76% of patients had an endoscopic response.(Reduction of patient inflammation or improvement in the extent of damage)；

4. 54% of patients were in endoscopic remission.(Almost complete mucosal healing/symptom resolution)。

   
   

Johnson & Johnson: Guselkumab

Guselkumab was approved by the FDA in 2017 for the treatment of adult patients with moderate to severe plaque psoriasis and was the first IL-23 inhibitor to receive FDA approval. It was later also approved by the FDA for the treatment of active psoriatic arthritis and moderately to severely active UC.

Johnson & Johnson announced the results of the Phase III GRAVITI study of Guselimumab, which aimed to evaluate the efficacy and safety of Guselimumab in patients with moderate to severe active Crohn's disease (CD) who had an inadequate response or intolerance to conventional therapies/biologics. The study included a 12-week induction period and a 36-week maintenance period, divided into three groups: placebo group, Guselimumab 400 mg SC q4w (x3) + Guselimumab 200 mg SC q4w group, and Guselimumab 400 mg SC q4w (x3) + Guselimumab 100 mg SC q8w group.

Results at Week 12 showed that 56.1% of patients in the trial group achieved clinical remission.(21.4% in the placebo group), and 41.3% of patients had an endoscopic response.(21.4% in the placebo group). In addition, compared with the placebo, the test group showed more significant clinical relief at the 4th week of treatment.(Indicates rapid effectiveness)。

At week 48, the clinical remission rates for the guselkumab 100 mg SC q8w group, 200 mg SC q4w group, and placebo group were 60.0%, 66.1%, and 17.1%, respectively; 44.3%, 51.3%, and 6.8% of patients had endoscopic response, respectively; and 30.4%, 38.3%, and 6.0% of patients achieved endoscopic remission, respectively.

Among the four IL-23 inhibitors currently approved for marketing, only risankizumab has been approved for the CD indication. The dosing regimen is as follows: induction doses are administered via intravenous infusion at weeks 0, 4, and 8, and maintenance doses are given subcutaneously every 8 weeks starting from week 12. The Phase III clinical trial of mirikizumab also adopted the same regimen of intravenous infusion during the induction period and subcutaneous administration during the maintenance period. In contrast, the GRAVITI study of guselkumab, which uses subcutaneous injection throughout the treatment process, presents a significant advantage and may offer patients a more convenient method of administration. This is also the point that Johnson & Johnson emphasized this time.

Summary

CD is prone to recurrence, has a longer treatment cycle, and relatively high treatment costs, significantly impacting the patient's life and financial situation, thus being dubbed as a "disease of affluence." The cause of this disease...CurrentlyIt is still unclear, but the incidence rate shows significant regional differences. It was previously more common in developed countries/regions in Europe and America, and in recent years, the incidence rate in China has been increasing year by year. The disease is commonly seen in adolescents, with an average age of patients ranging from 15 to 25 years.

Relevant disease diagnosis and treatment guidelines indicate:Despite significant advancements in the treatment drugs for CD in recent years, the "ceiling" of treatment efficacy still cannot be surpassed, with most reports on endoscopic effectiveness ranging from 40% to 60%. In addition to the currently available biologics and small molecule drugs, research hotspots now include multi-target drugs, combination therapies for refractory CD, fecal microbiota transplantation, stem cell injection treatments, and the exploration of new therapeutic target drugs. Moreover, multiple studies have shown that combination therapy with biologics can improve treatment outcomes compared to using them alone.

References:

1.Official Websites of Various Companies

Cover image source: pixabay

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