‘Zeposia best for ulcerative colitis patients with failed treatment experience’

There are people experiencing difficulty in everyday life due to unspeakable pains, such as diarrhea, bloody stool, fecal urgency, and stomachache. They are patients with ulcerative colitis.

Ulcerative colitis is a severe disease that not only gives pain to patients in everyday life but accompanies a high risk of developing asthma, anemia, connective tissue-related diseases, coronary artery disease, and colon cancer compared to healthy people.

However, it is difficult to cure completely, and symptoms improve and worsen repeatedly.

Recently, treatment options with various mechanisms have been developed, including TNF (tumor necrosis factor) inhibitors, integrin inhibitors, interleukin inhibitors, and JAK (Janus kinase) inhibitors, for moderate-to-severe ulcerative colitis patients who cannot be treated fully by existing general treatments, such as 5-ASA, immune controllers, and corticosteroid.

Among them, BMS provides a new oral treatment option by releasing Zeposia (ozanimod), the first sphingoshine 1P (S1P) receptor controller in inflammatory bowel disease (IBD), for patients who have to receive conventional therapy for a long time.

Against this backdrop, Korea Biomedical Review met with Diego Silva, vice president for global medical at BMS, who recently visited Korea, to learn about the development history of Zeposia and the drug’s advantages, as well as BMS’s plan in immunological diseases.

Question: The market for treating ulcerative colitis has already been filled with treatments with various mechanisms. We are curious why you jumped into the almost saturated market.

Answer: If there are many drugs available, there is also a lot of room for different families of drugs to suit each patient's characteristics. But various existing treatments are often biological drugs and injections. From the patient's standpoint, it is characterized by the burden of using (injections). Patients need to control their symptoms at the beginning of treatment and use the medication for up to 50 years, so they have no choice but to consider whether it is a drug that manages risks well, such as safety.

As a result of the BMS survey, many patients are hesitant to move on to other biological drugs, including anti-TNF drugs, or they feel burdened with injections, using drugs developed previously, including 5-ASA and corticosteroids.

Besides, inflammatory bowel diseases like Crohn’s disease and ulcerative colitis are ailments with an increasing prevalence worldwide, including in the United States, Europe, and Korea. BMS thinks there are huge unmet needs in this area. Some people in their 20s have inflammatory bowel disease. In this case, it deals a heavy blow to them in building their lives and in the productive activities of supporting themselves and their families.

Notably, ulcerative colitis and other inflammatory bowel diseases have symptoms like diarrhea, gastrointestinal problems, and bloody stool, and patients find it hard to discuss them openly, even with doctors. So, naturally, they experience difficulties maintaining interpersonal relationships and developing careers. Therefore, BMS judged it to be an area with enormous unmet needs and has invested much in providing solutions for inflammatory bowel disease patients.

Q: Could you explain the background for developing Zeposia?

A: Zeposia is an agonist that activates sphingoshine 1P receptors (S1P 1R and S1P 5R), suppressing immune function by reducing the number of peripheral lymphocytes. The concept of trying to control S1P has been around for quite a while. The first idea was presented in Japan 20 years ago.

It was first developed and licensed for multiple sclerosis in neurology. In the field of neurology, this mechanism has already been used for 13 years, from 2010 to the present. Therefore, we have come to develop the drug as it would provide another excellent treatment option if young patients, who find it burdensome to move to injections, can use an established and effective oral medication with excellent drug resistance in inflammatory bowel disease.

To sum up, we have come to develop Zeposia, considering a safe and effective oral treatment with good drug resistance can become an attractive treatment option for young people with inflammatory bowel diseases.

Q: What are the special features of Zeposia?

A: Zeposia showed good results for both early and late-phase patients. Doctors need to find the best solution for patients. When physicians find it challenging to find the most optimal solutions for their patients, Zeposia proved it could be the “best” option for patients who have failed after existing conventional treatments with various persuasive data.

The True North study, which compared and evaluated Zeposia and placebo in moderate-to-serve ulcerative colitis patients, included patients both with and without records of using biological drugs, and the former group outnumbered the latter. As a result of the study, Zeposia’s effects were twice higher in patients without records of using biological treatments than those with such records.

Zeposia is competitive because it works far faster than existing treatments. In the True North study, they analyzed patients every week during the inducing period. They found the gap in efficacy widen between the Zeposia group and the placebo group from the second week of treatment. Such differences appeared even before the second week if they had expanded the dose sufficiently.

For doctors, it's also important to know how consistently they can use the treatment. Ideally, they need a treatment they can use as quickly and consistently as possible for a long time. Zeposia is one such treatment.

Q: What kind of treatment do you want Zeposia to establish itself in the treatment of ulcerative colitis?

A: From the medical director’s viewpoint, Zeposia is suitable for patients who simultaneously feel the burden of disease and treatment. These patients find it quite burdensome to proceed with advanced treatments or those using injections. Accordingly, they are in a difficult situation where they must use steroids and suffer side effects.

This notwithstanding, they have a sense of rejection toward moving to injections and barely endure symptoms without dissolving symptoms. Unfortunately, these are one of the groups that need Zeposia most.

Q: What are your next pipelines in inflammatory bowel disease?

A: BMS is investing heavily in the gastrointestinal area and thinks it has sufficient capacity to become a leader in this field with existing pipelines alone. We are conducting various clinical trials in the inflammatory field, such as ulcerative colitis and Crohn’s disease.

Besides, we are gathering participants in the phase 3 clinical trial of cendakimab, an interleukin inhibitor related to eosinophilic esophagitis.

Q: What is your company’s plan concerning immunology?

A: BMS thinks it could be a global leader in the immunological area in the next 10-15 years. We are conducting various clinical trials in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and eosinophilic esophagitis. In the pipelines in the immunological area alone, it is developing 15 products ranging from preclinical stage to phase 1 to 3 clinical trials.

BMS is investing heavily in immunological diseases because they have huge unmet demands. Because we are a company with the capacity and talent to develop innovative new drugs for immunological diseases, we would like to be helpful in this area by making the most of them. BMS is confident it can be a powerful leader in treating immunological diseases.