Johnson & Johnson Reveals Promising Results for JNJ-2113 in FRONTIER 2 Study

Johnson & Johnson has unveiled findings from the FRONTIER 2 study at the 2024 American Academy of Dermatology Meeting in San Diego, California. It served as a long-term extension of the phase 2b FRONTIER 1 clinical trial assessing JNJ-2113, a targeted oral peptide designed to block the IL-23 receptor. IL-23 plays a crucial role in pathogenic T-cell activation in moderate to severe plaque psoriasis and is implicated in various IL-23-mediated diseases.¹

In FRONTIER 2, JNJ-2113 demonstrated sustained high rates of skin clearance over 52 weeks in adults with moderate to severe plaque psoriasis. The study measured response rates using the Psoriasis Area and Severity Index (PASI), with the highest PASI 75 response observed in the 100 mg twice-daily group. Response maintenance was consistent across key secondary endpoints, including PASI 90, PASI 100, Investigator's Global Assessment (IGA) 0/1, and IGA 0.

Safety data from the long-term extension study (Week 16 through Week 52) showed consistency with FRONTIER 1, with 58.6 percent of patients experiencing adverse events (AEs). Notably, there was no evidence of a dose-dependent increase in AEs, including gastrointestinal disorders. Commonly reported AEs included nasopharyngitis, upper respiratory tract infection, and COVID-19, the latter accounting for 5.3 percent of cases. Serious AEs were uncommon, occurring in 4 percent of combined JNJ-2113 patients through Week 52, and were considered unrelated to study treatment.

Lloyd Miller, MD, PhD

Lloyd Miller, MD, PhD, vice president of immunodermatology disease area leader at Johnson & Johnson shared insights with Dermatology Times during an interview at AAD on new data since our last interview about FRONTIER 1 data.²

Dermatology Times: Can you elaborate on the significance of the maintenance of high rates of skin clearance with JNJ-2113 through 52 weeks, particularly in terms of the PASI responses, and how these results compare to other available treatments for moderate-to-severe plaque psoriasis?

Miller: Data from the JNJ-2113 FRONTIER 2 study showed unprecedented maintenance of response through week 52 that sets a new efficacy standard for oral therapies and delivers competitive PASI and IGA results compared with the leading advanced biologic therapies for moderate to severe plaque psoriasis. Skin clearance as measured by PASI 75 and higher-bar PASI 90 and 100 responses at 16 weeks were maintained at 52 weeks with no new safety signals across all JNJ-2113 treatment groups. These findings suggest the potential for JNJ-2113 to continue delivering clinically meaningful results, and addresses the high unmet need for a novel, durable, and convenient oral therapeutic option for people living with moderate to severe plaque psoriasis.

We also saw maintained improvement in patient reported outcomes, including the Psoriasis Symptoms and Signs Diary (PSSD) and the Dermatology Life Quality Index (DLQI). These continued improvements are very important because living with plaque psoriasis can be a challenge and impact life beyond a person’s physical health, including emotional health, relationships, and handling the stressors of life.

Dermatology Times: The safety profile of JNJ-2113 in FRONTIER 2 appears consistent with FRONTIER 1, with a low incidence of adverse events and no evidence of dose-dependent increase. However, COVID-19 was reported in 5.3 percent of patients. Could you provide more insight into the implications of this finding and any considerations for patients receiving JNJ-2113 in the context of the ongoing pandemic?

Miller: The safety profile of JNJ-2113 in FRONTIER 1 and FRONTIER 2 were consistent, with no trends of any dose-related adverse events. The most common adverse events were nasopharyngitis, upper respiratory tract infections and COVID-19 infection. In FRONTIER 1, the percentages of COVID-19 infections were similar between JNJ-2113 treated groups and placebo. In FRONTIER 2, there was no placebo group as all patients crossed over to JNJ-2113 and the 5.3 percent of patients that developed a COVID-19 infection was likely due to the normal rates of COVID-19 infection that occurred when the trial were conducted. We will continue to monitor for adverse events and safety in the larger number of patients in the Phase 3 ICONIC Trials with JNJ-2113.

Dermatology Times: The continuation of the dosing regimen for patients who originally received JNJ-2113 in FRONTIER 1 and the switch to JNJ-2113 100 mg once daily for those in the placebo group were noted in FRONTIER 2. How do these dosing decisions impact the interpretation of the study results, and what rationale guided these choices?

Miller: In FRONTIER 2, patients who originally received JNJ-2113 in FRONTIER 1 continued with the same dosing regimen they received in the earlier part of the trial. The protocol for FRONTIER 2, also included a cross over design in which patients who were originally in the placebo group received JNJ-2113 100 mg once daily. We were pleased to see that these placebo patients who were switched to JNJ-2113 at the 100 mg dose achieved virtually the same level of improvements as patients in FRONTIER 1 on that same dose.

Based on the pharmacokinetic and pharmacodynamic data from the five different once-daily and twice-daily dosing regiments in FRONTIER 1, we believe that the 200 mg dose that we are using for the Phase 3 ICONIC Trials will have the maximal degree of efficacy of JNJ-2113 in a once-daily dosing regimen. 

Dermatology Times: Laura Ferris, MD, PhD, professor of dermatology at the University of Pittsburgh, mentioned the potential for JNJ-2113 to address the high unmet need for a durable and convenient oral therapeutic option in moderate to severe plaque psoriasis. In your opinion, based on the FRONTIER 2 results, how does JNJ-2113 stand out in terms of its clinical meaningfulness and convenience compared to existing treatment options?

Miller: Despite advances in therapy and multiple approved treatment options, many patients with moderatetosevere plaque psoriasis are eligible for but are not currently receiving advanced therapies; in part, they may not be comfortable with or able to use injected or infused treatments, and there remains an unmet need for an effective, safe oral therapeutic option. An oral therapy that can inhibit the IL-23 pathway by directly targeting the IL-23 receptor could help address the needs and preferences of patients, and may offer greater freedom, with the aim of driving greater adoption of advanced treatment.

With these promising longer-term results for JNJ-2113, we are excited by the possibility of unlocking a new and potentially differentiated oral treatment option that specifically and uniquely targets the well-established IL-23 pathway, which underpins the inflammatory response in psoriasis disease pathogenesis. Our focus is on developing novel, effective therapies to ensure patients with immune-mediated conditions can one day achieve remission, and we are pleased that this data suggests we are moving in that direction.

Dermatology Times: The announcement mentions the initiation of the Phase 2b ANTHEM-UC study to evaluate JNJ-2113 in participants with ulcerative colitis. What led to the decision to explore the potential of JNJ-2113 in this condition, and are there any insights from the IL-23-mediated diseases spectrum that could inform expectations for JNJ-2113 in ulcerative colitis?

Miller: Findings from the FRONTIER 1 and 2 clinical trials suggest the potential of JNJ-2113 across the spectrum of additional IL-23-mediated diseases. Accordingly, J&J has initiated the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis (UC). It is a prospective randomized placebo controlled blinded study in which we will evaluate the efficacy and safety of different doses of JNJ-2113. We are eagerly awaiting the results from that study to better understand the potential of JNJ-2113 in UC.

Drawing from a 2-decades-long legacy of immunology innovation, J&J is focused on developing novel, effective therapies to ensure patients with immune-mediated conditions can one day achieve remission. We are committed to using our immunology expertise to advance understanding of the IL-23 pathway and unlock new treatments for patients with immune-mediated conditions, including UC.

References

1. New data shows JNJ-2113, the first and only investigational targeted oral peptide, maintained skin clearance in moderate-to-severe plaque psoriasis through one year. Johnson & Johnson. March 9, 2024. Accessed March 9, 2024. https://www.prnewswire.com/news-releases/new-data-shows-jnj-2113-the-first-and-only-investigational-targeted-oral-peptide-maintained-skin-clearance-in-moderate-to-severe-plaque-psoriasis-through-one-year-302084693.html
2. Andrus E, Miller L. Lloyd Miller, MD, PhD: Delving Into JNJ-2113 Data for Plaque Psoriasis. Dermatology Times. February 19, 2024. Accessed March 10, 2024. https://www.dermatologytimes.com/view/lloyd-miller-md-phd-delving-into-jnj-2113-data-for-plaque-psoriasis