Lloyd Miller, MD, PhD: Delving Into JNJ-2113 Data for Plaque Psoriasis

Protagonist Therapeutics, Inc. and Johnson & Johnson recently announced the publication of data and findings from the phase 2b FRONTIER 1 trial (NCT05223868) investigating JNJ-2113 in adults with moderate-to-severe plaque psoriasis (PsO) in the New England Journal of Medicine.

In the study, patients receiving 100 mg of JNJ-2113 twice daily showed significant improvements in plaque psoriasis symptoms. Additionally, 79% of patients achieved a PASI-75 response, indicating a 75% or more reduction in Psoriasis Area and Severity Index score, and 64.3% achieved an IGA score of 0/1, suggesting minimal skin lesions. Patient-reported outcomes also improved, with better symptom severity and quality of life reported by week 16.

Read more from Dermatology Times here.

Lloyd Miller, MD, PhD, is vice president and the disease area lead for immunodermatology for Johnson & Johnson Innovative Medicine. Lloyd, a clinician scientist and board-certified dermatologist, recently spoke with Dermatology Times to discuss the significance and future implications of the positive data.

Transcript

Lloyd Miller, MD, PhD: My name is Lloyd Miller. I am the vice president and the disease area lead for immunodermatology for Johnson & Johnson Innovative Medicine. I'm a clinician scientist by training and a board-certified dermatologist.

Dermatology Times: Can you elaborate on the significance of these published findings in regard to treating plaque psoriasis?

Miller: First, let me state that the investigational JNJ-2113 is the first and only targeted all peptide that's designed to block the IL-23 receptor. We really understand through science and years of studying these diseases: IL-23 underpins the inflammatory response in psoriasis as well as other inflammatory diseases such as ulcerative colitis. JNJ-2113 is the only investigational oral therapy specifically targeting the IL-23 receptor, and and we believe that it will deliver the unprecedented combination of efficacy, safety, and convenience of an oral pill to people living with psoriasis, which will redefine expectations of what is possible.

I just think this is so important because the majority of patients living with moderate to severe plaque psoriasis or even ulcerative colitis either do not respond to their first line of therapy, or are eligible for but not receiving any advanced therapy. An oral therapy that can uniquely inhibit the underpinnings of the disease could help address the needs and preferences for patients and may offer greater freedom with the aim of driving greater adoption of advanced therapies, so getting many patients in remission. Johnson & Johnson has advanced JNJ-2113. In addition to the FRONTIER trial, we've moved into phase 3 development for moderate to severe plaque psoriasis as a once daily regimen, and we have initiated a phase 2b trial, a clinical trial for adults living with ulcerative colitis and other IL-23 mediated disease.

Dermatology Times: What makes JNJ-2113 unique when comparing it to existing treatments for plaque psoriasis regarding its method of action and more?

Miller: We're excited for a number of reasons about JNJ-2113. First of all, the phase 2b FRONTIER-1 was a dose-ranging study in which we tested multiple doses of JNJ-2113, and they were daily or twice daily doses. We tested 25 milligrams daily, 25 milligrams twice daily, 50 milligrams, and 100 milligrams once a day, and 100 milligrams twice daily. Coming out of the study, some of the results gave us, I would say, a lot of excitement about the molecule and what it can deliver for patients.

First of all, the primary endpoint of the study was the PASI-75 response, which is the Psoriasis Area and Severity Index, of 75% improvement. At the highest dose, 200 milligrams twice daily, 79% of patients achieved that [endpoint]. If you look at even higher bar efficacy, like patients getting a PASI-90 response, 90% better, that number goes up to almost 60% of patients reaching PASI-90. If you look at PASI-100, the highest bar, so 100% improvement, basically clear skin, 40.5% of patients reached that level of efficacy. We're very excited about the clinical efficacy as measured by the investigator a scoring system of the PASI.

We're also excited about that we saw similar responses in patient reported outcomes, such as the Psoriasis Symptoms and Signs Diary, the PSSD, or in the Dermatology Life Quality Index, we saw really good responses there, and patients are reporting that they're feeling better. I'll give you just one example with the Dermatology Life Quality Index. We saw significant [number of] patients that after 16 weeks of treatment on JNJ-2113, they reported scores of 0/1, which means that their psoriasis had either little or no impact on their quality of life. We're not just treating the skin and making the skin better; the patients are actually actually feeling better. Johnson & Johnson, we're just so focused on getting patients in remission, and having not just their their clinical disease get better in their skin, but also knowing that their symptoms and signs of the disease are also getting better. It's nice seeing that consistency across all those endpoints.

I'll make one more point: We also looked at objective biomarkers in the study, the most significant one of being beta-defensin-2, which is a marker of psoriasis disease. It's a serum biomarker, so it goes down if disease gets better, and it also is particularly gets better in patients being treated on IL-23 and IL-7 therapies. We saw a really great decrease, very, very low levels and the highest level of decrease of the lowest levels of beta-defensin-2 were seen at that highest dose of JNJ-2113 of 100 milligrams twice a day. So again, the consistency across the clinician or investigator reported outcomes, the patient reported outcomes, and the objective biomarkers, when we see all those lined up a line up, we have a lot of confidence in this mechanism as being a real good way to treat patients going forward.

Dermatology Times: Can you provide insights into the regulatory pathway and timeline for not only potential future approval, but future studies for JNJ-2113 in plaque psoriasis?

Miller: We've already launched our phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients. I do want to highlight that this is the first pivotal study that we know about that has included adolescents in the pivotal phase 3 studies. We're very excited about that and worked very closely with regulators. We cannot just include adults, but also include adolescents, in our pivotal programs for registration and submission and eventual approval.

Two of these trials have launched already in 2023. One of them is the ICONIC-LEAD, which is a randomized control trial that will evaluate the safety and efficacy of JNJ-2113 compared to placebo with moderate to severe plaque psoriasis, and we're using a higher bar efficacy of PASI-90, as well as an Investigator Global Assessment score of 0/1. We want to see at least a 2 great improvements, and those are our 2 coprimary endpoints.

We have another study that was launched as part of our phase 3 ICONIC program called ICONIC TOTAL, another randomized control trial where we're evaluating again, the efficacy and safety of JNJ-2113 compared to placebo, but this is for psoriasis patients that have at least moderate severity of psoriasis in special sites, special areas, such as the scalp, the genital region, or the palms of the hands or soles of the feet. Overall, we want to see an IGA score of 0/1, or at least a 2-grade improvement as the primary endpoint in that study.

Our other plans are 2 other studies that will be available on clinicaltrials.gov which are comparator studies. We're comparing JNJ-2113 with another drug, a TYK2 inhibitor called deucravacitinib as well as placebo in a head-to-head manner. We're looking to see how well the efficacy and safety of JNJ-2113 will compare with placebo and deucravacitinib. That's basically our overall, right now, plans for our phase 3 development to this date that I can announce in psoriasis.

For the regulatory path, we are going for that higher bar efficacy, again, as I mentioned, a PASI-90, where there are patients with moderate to severe plaque psoriasis and an IGA score of 0/1. That's because that's the efficacy we've already seen with the FRONTIER data suggesting that we are in that range of efficacy.

Dermatology Times: In what ways do you anticipate JNJ-2113 impacting the landscape of treatment options for plaque psoriasis, both in the United States and globally?

Miller: We're just very excited about it as a treatment for patients and even as me as a dermatologist, how patients would view this therapy. First of all, it's an oral pill, so that gives the patients a lot of freedom of when they can take that pill, and they know if any side effect was to develop, they can stop that pill and not take another pill the next day.

I would say patients right now, the treatment of psoriasis has mostly been with injectable biologic type therapies. Those patients have to carry around needles, they have to be stored in the refrigerator. They often have to inject themselves, sometimes once a week, every other week, could be every month, every few months. Again, a lot of patients have a fear of needles; a lot of patients don't like taking something as strong. They just don't want to take a drug that's delivered with the needle. Some actually have a needle phobia. We also think in children, needles might be a very difficult proposition, and for children, taking an oral pill might be a better option for children. Having a drug like JNJ-2113, we think, has a lot of potential and could really change the paradigm of how we treat psoriasis.

I'll also mention that in our FRONTIER study, there were no trends in any adverse events seen with JNJ-2113 with any of the doses as well as with placebo, so they were basically comparable. The highest rates of adverse events we saw, which were basically equivalent between JNJ-2113 and placebo, were with COVID-19 infections nasopharyngitis. There were some cases of gastrointestinal problems, but very, very low levels, and again, no difference between placebo and JNJ-2113. From a safety perspective, we also think this will also be a very safe and hopefully effective option for patients.

Dermatology Times: What else would you like clinicians and those in the dermatology space to be aware of or know?

Miller: J&J, I do want to just cover again, that we are focused on the overall well being of patients. In many of our studies, and actually in all of our studies, we are going to not just focus on the signs, and I would say how the psoriasis looks, but we're also asking a lot of questions about how patients are functioning in many different aspects of their lives. We are doing a lot of patient reported outcomes in addition to our looking at the disease itself. We also are excited to have that special site study in the pivotal study. We are measuring patients that are really bothered by scalp psoriasis, or hand and foot psoriasis, or psoriasis in the sensitive areas, as in the genitals. That's just so important for patients. So I think that level of focus, and then the comparator study, again, showing that this could be a transformational therapy for patients. I do want to focus on the how big the oral focus is, and we're seeing that there's a strong provider and patient preference for orals for the reasons I mentioned earlier. So together, we really see the JNJ-2113 answers or provides a solution for patients with psoriasis that they don't currently have and we hope will be a good option for patients in the future.

[Transcript has been edited for clarity.]