Mirikizumab

Tremfya’s efficacy looks better but not too different from the results achieved by AbbVie’s rival IL-23 inhibitor Skyrizi in its own UC maintenance trial. (Johnson & Johnson) Editor's Note: The story was originally published on May 20 and was updated on May 21 to include Tremfya's data in Crohn's disease.  The biologics market for inflammatory bowel disease is continually getting more competitive, and now Johnson & Johnson’s Tremfya is the latest medicine angling to make a mark in the space. Tremfya, at two different doses, beat J&J’s own Stelara in patients with moderately to severely active Crohn’s disease (CD) when it came to improvements seen under an endoscope, according to phase 3 results presented at Digestive Disease week (DDW) 2024. After 48 weeks of treatment, 37.2% and 33.2% of patients who received subcutaneous Tremfya at 200mg every four weeks and 100mg every eight weeks, respectively, achieved endoscopic remission. The rate was 24.7% for those who received Stelara. Tremfya’s magnitude of improvement over Stelara appeared smaller when considering clinical remission rates. The newer IL-23 inhibitor helped 70.3% and 65.4% of patients, respectively, reach clinical remission. The older IL-12/23 blocker managed a 62.9% rate of clinical remission. Tremfya was also better than placebo on two co-primary endpoints of the GALAXI 2 and GALAXI 3 trials. Both composite endpoints included clinical responses at week 12, along with either clinical remission or endoscopic responses at week 48. In the increasingly crowded IL-23 space, AbbVie’s Skyrizi was the first treatment to reach CD with an FDA approval in June 2022. Last year, AbbVie put up its own Stelara head-to-head win, showing that 61% of Skyrizi takers achieved clinical remission at week 48, versus 41% for Stelara. Skyrizi also doubled the endoscopic remission rate to 32%. Also at DDW, Eli Lilly unveiled CD data for its Omvoh, which in October became the first IL-23 drug approved in ulcerative colitis (UC), the other form of inflammatory bowel disease. But the Lilly drug was pitted against placebo and doesn’t yet have Stelara head-to-head data. Meanwhile, as J&J awaits an FDA approval decision for Tremfya in UC, the company additionally unveiled positive phase 3 data showing the drug works as a maintenance therapy for the disease. The IL-23 inhibitor helped significantly more patients with moderate to severe, active UC achieve clinical remission after 44 weeks of treatment compared with placebo, according to results from the phase 3 QUASAR maintenance study shared during DDW. Remission was achieved among 50% and 45.2% of patients who received Tremfya at 200mg every four weeks and 100mg every eight weeks, respectively. The rate was 18.9% among those who switched to placebo from infused Tremfya. Tremfya’s efficacy looks better but not too different from the results achieved by Skyrizi in its own UC maintenance trial. In the phase 3 COMMAND trial, 40% and 38% of patients who received subcutaneous Skyrizi at 180mg and 360mg every eight weeks, respectively, achieved clinical remission after a year of treatment. The number was 25% for those who transitioned to placebo after Skyrizi infusion as induction. For Tremfya in the latest UC study, 33.7% and 34.6% of patients on the two regimens, respectively, showed normal intestinal mucosa, or what's known as endoscopic remission. That compared with 15.3% of those in the Tremfya withdrawal group. All told, both Tremfya regimens met all nine major secondary endpoints in the UC study. The rate of patients with more than one adverse event was 70% and 64.5% for the two Tremfya doses, respectively, versus 68.2% for placebo. “These data suggest the potential of [Tremfya] to provide durable, clinical remission and improve important high-bar endpoints such as endoscopic remission to the point of normalization and histologic remission, which represent the kind of progress needed in new treatments for this inflammatory bowel disease,” David T. Rubin, M.D., from University of Chicago and lead investigator of the QUASAR study, said in a statement Monday. Before the latest maintenance readout, the QUASAR induction study had found that Tremfya led to a 22.6% rate of clinical remission at week 12, versus 7.9% for placebo. Based on the QUASAR findings, J&J in March filed Tremfya for FDA approval in UC. The company on May 1 said it has applied for both UC and CD with the European Medicines Agency. Meanwhile, AbbVie submitted Skyrizi to the FDA in August for a potential UC expansion; the company is expecting a decision in the middle of this year. The drug already boasts a Crohn’s approval. J&J is shoring up Tremfya’s indications as Stelara inches toward its patent cliff. With $10.9 billion sales in 2023, Stelara was J&J’s biggest brand, accounting for 12.8% of the company’s total revenue last year. European Stelara biosimilars are expected to debut this year, with U.S. copycats expected to be available in early 2025. Ahead of Stelara biosimilar launches, Tremfya has been gaining traction commercially. In the first quarter, Tremfya sales jumped 26% year over year to $808 million, while Stelara’s sales flattened at $2.45 billion. Tremfya now generates more sales in its approved indications—plaque psoriasis and psoriatic arthritis—than Stelara does in those two fields, J&J CEO Joaquin Duato said on the company’s first-quarter earnings call in April. Nevertheless, Skyrizi leads the U.S. biologic psoriasis market with a total prescription share above 35%, which is more than double the share of the next biologic competitor, AbbVie’s chief commercial officer Jeff Stewart said on the Illinois pharma’s first-quarter call in April. In IBD, Skyrizi has already achieved market share leadership in Crohn’s in the U.S., and it’s on track to add more than $1 billion in growth this year, Stewart said.

At the study's one-year mark, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of mirikizumab patients, respectively. Following last year’s hard-won ulcerative colitis nod for Eli Lilly’s Omvoh, also known as mirikizumab, the Indianapolis-based drugmaker is padding the case for its antibody’s next potential immunology approval. Lilly on Tuesday reported that mirikizumab aced both co-primary endpoints and all major secondary endpoints after 1 year of testing in the phase 3 VIVID-1 trial in Crohn’s disease. Notably, Lilly’s drug appeared to work in patients for whom previous biologics had not, according to data presented at Digestive Disease Week in Washington D.C. Specifically, 39.3% of bio-naïve patients (those who had never tried a biologic) and 36.7% of bio-failed patients (those for whom biologics either did not or stopped working) on mirikizumab achieved composite patient-reported clinical response at the 12-week mark and endoscopic response after 1 year compared to 11.8% and 6.2% of bio-naïve and bio-failed patients on placebo, respectively. Further, 47.3% and bio-naïve and 43.4% of bio-failed patients on mirikizumab achieved clinical remission at week 52 according to the Crohn’s Disease Activity Index (CDAI), versus 26.5% and 12.4% of patients on placebo, Lilly said. Overall, at the one-year mark, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of mirikizumab patients, respectively. Meanwhile, when pitting mirikizumab against J&J’s Stelara (ustekinumab), patients on Lilly’s drug saw “nominally statistically significant higher rates” of clinical remission and endoscopic response at week 52, Lilly pointed out. The company caveated that mirikizumab did not achieve superiority to Stelara for endoscopic response. "After one year of treatment, more than one-half of patients treated with mirikizumab achieved clinical remission and nearly one-half achieved endoscopic response,” Mark Genovese, M.D., SVP of Lilly immunology development, said in a statement. “Remarkably, the majority of patients who achieved either of these endpoints, achieved both together.” Ahead of the data drop, Lilly says it submitted an application for mirikizumab in Crohn’s disease with the FDA and European Medicines Agency earlier this year. The company also plans to ship filings to other regulators around the world. Aside from the VIVID-1 study, Lilly is also testing mirikizumab in other Crohn’s populations, including children. Upon winning its first approval at the FDA in October, mirikizumab, under the brand name Omvoh, became the first IL-23 inhibitor to enter the crowded ulcerative colitis field, which already counts biologics from AbbVie, Johnson & Johnson and Takeda among its ranks. The approval followed a rejection last April when the FDA snubbed the drug over manufacturing problems uncovered during a preapproval inspection. Over the course of 2023, mirikizumab also picked up ulcerative colitis green lights in Europe and Japan, plus a reimbursement recommendation in England.