PharmaShots Interview: Eli Lilly's Dr. Lotus Mallbris Shares Insights on Mirikizumab

In a recent interview with PharmaShots, Dr. Lotus Mallbris, the Vice President of Immunology Development at Eli Lilly shares her insights and highlights on Mirikizumab.

Shots:

@52wks. ~60% achieved endoscopic responses (58.5% in IV dosing group and 58.7% in the SC group) while 45% + achieved PRO remission (46.3% in the IV group and 45.6% in the SC group)
If approved for IBD indications, mirikizumab a biologic entity that blocks the activity of the IL-23 cytokine could be one of the first IL-23s approved for ulcerative colitis, a disease state with fewer biologic treatment options, as well as one of the first of this class to be approved for Crohn's disease
Lilly is currently investigating mirikizumab in P-III clinical trials. Lilly expects topline results for the P-III induction data in UC in the spring of 2021 and for the P-III Crohn's data in 2022.

Tuba: How was your virtual experience at UEG week? Can we have a quick highlight on the data of mirikizumab presented at UEG Week?

Lotus: I was very pleased with my experience at UEG Week; although the format was different than previous years considering the meeting was entirely virtual, it was a great opportunity to learn about the latest innovation in the gastroenterology space. Lilly had the opportunity to present new efficacy and safety data from the Phase 2 SERENITY study evaluating mirikizumab in patients with moderately to severely active Crohn's disease at this year's virtual UEG Week. These are the first 52-week data for mirikizumab in Crohn's disease (CD) and the results continue to build upon the data already presented in ulcerative colitis (UC). These results are an important part of the clinical development program for mirikizumab, and Lilly hopes these data can provide optimism for those living with Crohn's disease.

At 52 weeks, patients who showed endoscopic improvement at 12 weeks and continued treatment with mirikizumab achieved the following results:

Endoscopic response: Nearly 60% of patients achieved endoscopic response (58.5% in the randomized IV dosing group and 58.7% in the SC group).
Patient-Reported Outcomes (PRO) remission: More than 45% of patients achieved PRO remission (46.3% in the IV group and 45.6% in the SC group).

Among the subset of patients who achieved an endoscopic response at Week 12, 69.6% and 66.7% in the IV (n=23) and SC (n=24) groups, respectively, also had endoscopic response at Week 52. Additionally, among those with endoscopic remission at Week 12, 50.0% and 64.3% in the IV (n=6) and SC (n=14) groups, respectively, also had endoscopic remission at Week 52. These Phase 2 data support and reinforce the potential for mirikizumab in the ongoing, pivotal VIVID Phase 3 program as a potential treatment for patients with Crohn's disease.

Tuba: What are the other treatments across Lilly's immunology portfolio for transforming the treatment experience of patients with autoimmune diseases?

Lotus: We recognize there are still significant unmet needs, as well as personal and societal costs, for people living with autoimmune diseases and our goal is to minimize the burden of disease and help patients find treatments that offer meaningful improvements. Our immunology portfolio includes first in class or first in disease molecules and we're investing in leading-edge clinical approaches across our deep pipeline, which also includes early candidates currently in Phase 1 and Phase 2 development. Through these treatments, we hope to one day offer therapeutic options for patients across ten disease areas:

Mirikizumab is an investigational treatment that is being studied for the treatment of adults with Crohn's disease, ulcerative colitis and moderate to severe plaque psoriasis.
Taltz® (ixekizumab) is approved for moderate to severe plaque psoriasis in adults and children, as well as active psoriatic arthritis, active non-radiographic axial and active ankylosing spondylitis in adults.
Olumiant® (baricitinib) is indicated for adults with moderately to severely active rheumatoid arthritis, and is being studied for moderate to severe atopic dermatitis (AD); systemic lupus erythematosus (SLE), which received Fast Track designation from the Food and Drug Administration (FDA); and alopecia areata (AA), which received Breakthrough Therapy designation from the FDA earlier this year.
Lilly recently announced a positive CHMP opinion by the European Medicines Agency's (EMA) for Olumiant in AD, and if approved, Olumiant could become the first oral JAK inhibitor available in the EU.
Lebrikizumab is a novel, investigational, a monoclonal antibody in Phase 3 studies to evaluate its safety and efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis.

Mirikizumab is an investigational treatment that is being studied for the treatment of adults with Crohn's disease, ulcerative colitis and moderate to severe plaque psoriasis.

Tuba: Are there any specific population or any group in which mirikizumab shows its higher and lower efficacy & safety?

Lotus: In addition to IBD, mirikizumab is also being studied in adults with moderate to severe psoriasis. Earlier this year, Lilly presented results from the Phase 3 OASIS-2 study, which showed mirikizumab met the primary and all key secondary endpoints versus placebo at Week 16 (superiority), as well as all key secondary endpoints versus Cosentyx® (secukinumab) at Week 16 (non-inferiority) and Week 52, including superiority in skin clearance at Week 52.

In the data presented at UEGW, mirikizumab demonstrated efficacy in adults with Crohns disease over 52 weeks of treatment. Additional studies in adults are ongoing, and Lilly expects Phase 3 Crohn's data in 2022.

Tuba: As Lilly is evaluating mirikizumab in three different indications i.e. psoriasis, UC & CD. Can we have a quick review on the clinical data related to the targeted disease?

Lotus: Mirikizumab is being studied for the treatment of immune diseases, including psoriasis, ulcerative colitis and Crohn's disease:

In psoriasis, Lilly presented results in July 2020 from the Phase 3 OASIS-2 study, which showed mirikizumab met the primary and all key secondary endpoints versus placebo at Week 16 and all key secondary endpoints versus Cosentyx® (secukinumab) at Week 16 and Week 52, including superiority in skin clearance at Week 52.
In addition to the data presented at UEGW this year, Lilly also expects topline results for Phase 3 Crohn's data in 2022, following positive endpoints being met at 12 weeks in its Phase 2 trial.
Lilly expects topline results for the Phase 3 induction data in ulcerative colitis in the spring of 2021.

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Tuba: As the market is flooded with multiple biologics in IBD, what is Lilly's strategy to position its therapy in CD?

Lotus: Inflammatory bowel disease (IBD), which included Crohn's disease and ulcerative colitis, affects more than 10 million people worldwide. Crohn's disease is a serious and difficult-to-treat condition, and there is a significant need for additional treatments that can address the challenging and painful symptoms of people living with Crohn's disease experience. In the study presented at UEG Week, patients treated with mirikizumab showed a response in both symptom relief and endoscopic response and remission at 52 weeks. Based on these Phase 2 data, we're optimistic Lilly is one step closer to providing relief for patients.

Tuba: AbbVie's Skyrizi, Johnson & Johnson's Tremfya and Allergan's Brazikumab, and Novartis Cosentyx are some competitors of mirikizumab. What are other potential threats to the therapy?

Lotus: Lilly does not comment on competitors or data/trials conducted by other companies.

Tuba: What are your major steps in the digital world to transform inflammatory bowel disease (IBD) care?

Lotus: Through key partnerships, we are investigating several different approaches to enhance patient care, including the use of wearable sensors to collect biometric data and help us understand how patients respond to medications. We're also leveraging artificial intelligence to better diagnose certain GI issues. Lastly, we're conducting research to determine how digital disease management tools can provide a better understanding of ones condition, so patients can have better discussions with their healthcare professional.

Tuba: As you select HealthVoyager as a winner of the digital health innovation challenge for inflammatory bowel disease. Can you highlight the specification of the digital tool you are working on and when can we expect its availability?

Lotus: HealthVoyager, an application developed by Boston Children's Hospital and Klick Health, was named the winner of Lilly's 2019 digital health open innovation challenge. The idea leverages a highly customizable software platform for doctors to create a personalized and immersive educational experience for patients living with inflammatory bowel disease (IBD). We are confident in the application's success and support the team in their pursuit of its development, as Lilly focuses on other priorities for people living with inflammatory bowel disease. For additional updates about HealthVoyager, please contact Sheryl Steinberg at Klick Health (ssteinberg@klick.com).

Tuba: How do you think mirikizumab will raise the standard of Lilly in the field of immunology?

Lotus: If approved for IBD indications, mirikizumab a biologic entity that blocks the activity of the interleukin 23 (IL-23) cytokine could be one of the first IL-23s approved for ulcerative colitis, a disease state with fewer biologic treatment options, as well as one of the first of this class to be approved for Crohn's disease.

We are excited about the data presented at UEG Week and are encouraged by these Phase 2 results. We look forwarding to continuing our clinical program for mirikizumab, and hope it, along with our already robust pipeline in immunology, will help raise the standard of care for those living with Crohn's disease.

Tuba: What would be the pricing of the mirikizumab to compete with the emerging threats of lower-priced biosimilars in the space?

Lotus: Lilly does not comment on future pricing strategy.

Tuba: When can we expect the availability of mirikizumab in the US & EU?

Lotus: We are currently investigating mirikizumab in Phase 3 clinical trials. Lilly expects topline results for the Phase 3 induction data in ulcerative colitis in the spring of 2021 and for the Phase 3 Crohn's data in 2022.

About Dr. Lotus Mallbris:

Lotus Mallbris, M.D., Ph.D., is the Vice President and Global Head of Immunology Product Development at Eli Lilly. She has joined Lilly in 2015 and leads the company's global clinical development and global medical affairs teams across the dermatology, rheumatology, and gastroenterology fields.