FDA pushes back on approving mirikizumab due to manufacturing issues

On 14 April, the FDA rejected Lilly’s biologic licence application (BLA) for their anti-interleukin (IL)-23, mirikizumab, which is in development for the treatment of ulcerative colitis (UC). While the FDA sent Lilly a complete response letter detailing issues pertaining to the proposed manufacturing of mirikizumab, the regulator raised no concerns about the clinical data package or label for the medicine. The recent setback dents mirikizumab’s chances to be the first among the IL-23 inhibitors to launch in the US for UC.

Anti-interleukin therapies are generally prescribed as second-line or third-line treatment in UC patients who have failed a biological drug. While Janssen’s Stelara is currently the only approved anti-interleukin therapy approved for UC in the US, this therapy’s mechanism of action, targeting both IL-12 and IL-23, means it is associated with a higher risk of immunosuppression compared to selective IL-23 inhibitor agents such as mirikizumab. The selective inhibition of the latter set of agents is seen as a key advantage over Stelara, and one that will help these agents to differentiate themselves in the crowded biologics space for UC. Other anti-IL-23 agents that are in late-stage development for UC include AbbVie’s Skyrizi (ustekinumab), Janssen’s Tremfya (guselkumab), and Boehringer Ingelheim’s Spevigo (spesolimab).

GlobalData anticipated mirikizumab to be approved in the US in 2023, but this recent development may push mirikizumab back behind other agents such as Skyrizi and Tremfya, which are anticipated to enter the US market in 2024 and 2025, respectively. According to GlobalData’s patient-based forecast model, Stelara is anticipated to have US sales of $525.5m in 2031 while mirikizumab is expected to reach US sales of $318.2m in 2031. Key opinion leaders (KOLs) interviewed by GlobalData mentioned that mirikizumab did have potential; many of them highlighted the selectivity it offers and the option it provides for patients who do not respond to Stelara.

Despite the recent setback, it is worth noting that mirikizumab has already been approved in Japan for the treatment of adults with moderate-to-severe UC. Additionally, the IL-23 inhibitor also received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) as a first-in-class treatment for adults with moderately to severely active UC. As the FDA has raised no concerns with the clinical profile of mirikizumab, Lilly could still stage a comeback with this agent as the first-to-market IL-23 inhibitor therapy for UC in the US. However, that will depend on how quickly Lilly can address the regulator’s manufacturing concerns. Lilly is also investigating mirikizumab in Crohn’s disease, so this holdup could help inform Lilly of future decisions to avoid further delays in the approval process.