In an interview with PharmaShots, Jan Wehkamp, M.D., Vice President, Disease Area Leader, Gastroenterology at Janssen Research & Development shared his views on the data regarding the safety & efficacy of Stelara (ustekinumab) for UC patients, including long-term symptomatic & corticosteroid-free remission rates from the UNIFI study.

Shots:

• The P-III UNIFI study evaluates the safety & efficacy of Stelara induction and maintenance dosing for the treatment of mod. to sev. active UC in adults who demonstrated an inadequate response to or were unable to tolerate conventional therapies
• Results:  55.2% of patients were in symptomatic remission @152wks. and 96.4% of patients in symptomatic remission @152wks. were corticosteroid-free
• Janssen continues to conduct research & development efforts to advance the treatment of gastroenterological disorders such as UC and CD

Tuba: Discuss the key points of the data of Stelara presented at ECCO.

Dr. Jan Wehkamp: Most importantly, we perform long-term studies of medications like this because we know patients living with ulcerative colitis (UC) deserve therapies that can provide long-lasting efficacy, rapid response, and sustained remission without the need for long-term use of steroids. Study results from our new Phase 3 UNIFI long-term extension (LTE) show STELARA (ustekinumab) delivered sustained symptomatic remission rates among the majority of adult patients with moderately to severely active UC with no new safety signals present through nearly three years. Among patients who achieved clinical response at maintenance baseline and were randomized to STELARA 90mg, every eight weeks (q8w) or every 12 weeks (q12w), 55.2 percent of patients were in symptomatic remission at week 152.

Among patients who had achieved clinical response at maintenance baseline and were randomized to STELARA 90mg every q8w or q12w, 96.4 percent (185/192) of patients in symptomatic remission at week 152 were corticosteroid-free. This is important because while short-term steroid use is very common for the treatment of inflammatory bowel disease (IBD) to help address inflammation, it is not advisable for the long-term management of the disease, as it can be associated with several debilitating side effects and comorbidities including increased blood pressure, the onset of diabetes, and decrease of bone strength. Results from the UNIFI study underscore not only the potential STELARA has in treating UC symptoms in the long term, but the importance of delivering treatment options that do not require the long-term use of corticosteroids. 

In terms of safety findings, safety was evaluated at week 156 for all patients (n=588) who were treated in the LTE. Findings showed no new safety signals were present. 

Tuba: What does long term extension study depict?

Dr. Jan Wehkamp: A long-term extension study allows researchers to better understand the safety, efficacy, and tolerability of medications in a clinical setting over at least 5 years. In the UNIFI study, results showed 55.2 percent of patients treated with STELARA were in symptomatic remission at week 152 and 96.4 percent (185/192) of patients in symptomatic remission at week 152 were corticosteroid-free.  

Tuba: Will these long-term data of the drug bring change for patients who are still struggling to manage their disease and achieve remission?

Dr. Jan Wehkamp: Despite recent substantial therapeutic gains, many patients living with UC still struggle to find lasting relief from their disease symptoms in the long term. We are hopeful that the results of the UNIFI study can inform physicians and their patients about the potential role that STELARA has as a long-term treatment option in adults with moderately to severely active UC.

Tuba: Discuss the study design of the P-III UNIFI Trial.

Dr. Jan Wehkamp: UNIFI is a Phase 3 study designed to evaluate the safety and efficacy of STELARA induction and maintenance dosing for the treatment of moderately to severely active UC in adults who demonstrated an inadequate response to or were unable to tolerate conventional (i.e., corticosteroids, immunomodulators) or biologic (i.e., one or more TNF blockers or vedolizumab) therapies.

The induction study was of at least eight weeks duration for each participant. 523 intravenous induction responders were then randomized to subcutaneous maintenance therapy through 44 weeks: 175 patients on placebo, 172 patients treated with STELARA 90mg every 12 weeks, and 176 patients treated with STELARA 90mg every 8 weeks. 284 STELARA patients who completed week 44 entered the LTE. Placebo patients were discontinued after week 44 unblinding.

Starting at week 56, randomized patients with UC worsening could adjust to STELARA treatment every 8 weeks. Efficacy was evaluated in randomized patients using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0).

Safety was evaluated for all 588 patients who were treated in the LTE, including the randomized and nonrandomized populations. Through week 156, 131 patients continued on placebo and 457 patients received STELARA. The nonrandomized population included STELARA induction nonresponders at week 8 who received subcutaneous STELARA and responded 8 weeks later and responders to placebo induction.

Tuba: Do you think your competition in this space (for example Humira) would have similar power to treat UC?

Dr. Jan Wehkamp:  There are many different treatment options available for patients living with moderately to severely active UC. Every patient is different, so there are several factors that go into choosing the best treatment option, some of which can include the severity of disease, symptoms, and quality of life. Ultimately, the treatment decision is up to a physician and their patient. We hope that these long-term STELARA data can help inform these decisions.

Tuba: What are the company's other efforts in treating gastroenterological disorders?

Dr. Jan Wehkamp: Janssen continues to conduct research and development efforts to advance the treatment of gastroenterological disorders such as UC and Crohn's disease (CD). In addition to UC, STELARA is approved for the treatment of adult patients (18 years and older) with moderately to severely active CD. We are also studying STELARA in treat-to-target settings in the STARDUST study, which is the first study to compare treat-to-target and standard care treatment strategies using endoscopy to guide dose adjustment in the treat-to-target group to help inform future treatment strategies. STARDUST is also the first to evaluate non-invasive intestinal ultrasound in an interventional setting.

Additionally, we are studying the efficacy and safety of TREMFYA(guselkumab) as a potential treatment option in adult patients with moderately to severely active CD with inadequate response or intolerance to conventional therapies and/or biologics in the Phase 2 GALAXI study. TREMFYA is also being studied in a Phase 2b/3 program in UC and in Phase 1 clinical trial in celiac disease. There are also other compounds in earlier-stage clinical studies, including an oral gut-selective pan-JAK inhibitor and an oral gut-restricted IL-23 receptor antagonist in Phase 2 development, and two oral IL-23 receptor antagonists candidates currently in Phase 1 clinical development.

Tuba: What makes Stelara unique from its other competitors? Discuss it in terms of its MOA.

Dr. Jan Wehkamp: STELARA is a fully human monoclonal antibody and is the first biologic treatment to selectively inhibit the interleukin (IL)-12 and IL-23 pathways. In targeting both IL-12/23 pathways, STELARA has been approved to treat a range of autoimmune diseases in various patient groups including adults and children six years and older with moderate to severe plaque psoriasis, adult patients (18 years or older) with active psoriatic arthritis, adult patients (18 years and older) with moderately to severely active CD and adult patients (18 years and older) with moderately to severely active UC.

 Tuba: Janssen planning any digital initiatives to attract more patients and for better patient adherence.

Dr. Jan Wehkamp: At Janssen, we recognize the importance of understanding patient needs and raising awareness of gastroenterological diseases. Currently, our teams are leading two patient-driven initiatives, 'Peace Within', intended to showcase Janssen's commitment to supporting people living with immune-mediated diseases such as IBD and the 'My IBD Journey' animation series, an online resource created by Janssen Immunology in collaboration with The European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) for IBD patients containing important information, hints, and tips on managing IBDs like UC and CD.

Additional Janssen digital patient initiatives include a podcast called 'Gutcast,' the first IBD podcast in Ireland with the mission of informing and empowering patients to manage their condition, and Janssen Italy's digital initiative 'Fatti Più In Là' ("Go further - Let's move away from Crohn's disease and ulcerative colitis") in collaboration with the National Association for Chronic Inflammatory Bowel Diseases.

Readers can also learn more about our commitment to gastroenterology here: https://www.janssen.com/gastroenterology

Source: Self Hacked

About Jan:

Jan Wehkamp is the Vice President, Gastroenterology Disease Area Leader at Janssen Research & Development 

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