In an interview with PharmaShots, Lloyd Miller, MD, Ph.D., Vice President, Immunodermatology Disease Area Leader at Janssen shares his views on the data presented at EADV 2021 about patients who switch to Tremfya (guselkumab) from Humira (adalimumab) in P-III VOYAGE 1 & 2 trials for PsO & also highlighting the P-III DISCOVER-1 & 2 trial for PsA

Shots:

• The P-III VOYAGE 1 & 2 evaluates Tremfya vs PBO and adalimumab in ~825 patients with mod. to sev. PsO who were candidates for systemic therapy or phototherapy
• The results showed that patients treated with Tremfya had greater improvements in the signs and symptoms based on PASI 90 response & IGA 0/1 @16wks. Additionally, post-hoc analyses also showed durable skin clearance responses and were well-tolerated for 5yrs.
• In P-III DISCOVER-1 & 2, the results showed that patients treated with Tremfya had greater improvements in the signs and symptoms of active PsA, including joint and axial symptoms based on ACR 20 response compared to PBO @24wks.

Tuba: Can we discuss the trial design & results of VOYAGE in detail?

Dr. Miller: VOYAGE 1 and VOYAGE 2 are important P-III, randomized, double-blind trials comparing TREMFYA® (guselkumab) with placebo and adalimumab in over 825 adults with moderate to severe plaque psoriasis (PsO) who were candidates for systemic therapy or phototherapy. The results showed patients treated with TREMFYA, a selective interleukin (IL)-23 inhibitor therapy, had greater improvements in the signs and symptoms of moderate to severe plaque PsO versus placebo and adalimumab based on Psoriasis Area Severity Index (PASI) 90 response and Investigator Global Assessment (IGA) 0/1 at week 16. The post-hoc analyses we presented at the European Academy of Dermatology and Venereology (EADV) also show that TREMFYA provided durable skin clearance responses and was well-tolerated for up to five years (week 252). With TREMFYA, the mean percentage improvement from baseline in PASI response at week 48 was 94% compared to 73.4% with adalimumab. At week 252, the mean percentage improvement from baseline in PASI response was 92.9% among patients who crossed over at week 48 from adalimumab to TREMFYA.

In the trial design, patients were randomized to receive either placebo, TREMFYA, or adalimumab, with crossover from placebo taking place at weeks 16 and 20, and crossover from adalimumab occurring at week 52 in VOYAGE 1, and weeks 28-72 in VOYAGE 2. PASI 90 and IGA 0/1 were the co-primary endpoints of both studies. In VOYAGE 2, we conducted additional efficacy assessments that included proportions of patients achieving PASI 75, PASI 100, and IGA 0 (clear skin) responses, a Dermatology Life Quality Index (DLQI) score of 0/1, and a Psoriasis Signs and Symptoms Diary score of 0, as well as changes in baseline in SF-36, Hospital Anxiety, and Depression Scale, and the Work Limitations Questionnaire scores.

Tuba: Let's also discuss the trial design and results of the DISCOVER study in depth.

Dr. Miller: DISCOVER-1 and -2 are Phase 3, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of TREMFYA in over 1,900 adult patients with active psoriatic arthritis (PsA). The results showed that patients treated with TREMFYA had greater improvements in the signs and symptoms of active PsA, including joint and axial symptoms based on the American College of Rheumatology 20 (ACR 20) response compared with placebo at week 24. TREMFYA treatment also resulted in lower mean scores for all six Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) components and greater improvements in Ankylosing Spondylitis Disease Activity Score (ASDAS) compared with placebo through week 24 and as early as week 8, with similar mean scores at week 52 in patients with axial symptoms and sacroiliitis. TREMFYA was shown to have improved the signs and symptoms of active PsA regardless of patient baseline characteristics. TREMFYA treatment was well-tolerated through one year, with a safety profile in PsA that is consistent with the one established in the five-year Voyage 1 and 2 trials in PsO.

Both DISCOVER studies consisted of a screening phase of up to six weeks, a blinded treatment phase of 52 weeks in DISCOVER-1, and approximately 100 weeks in DISCOVER-2 that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period in the weeks following. They also included a safety follow-up phase through weeks 60 and 112, respectively. In each study, multiple other clinical outcomes were assessed in addition to ACR20, including ACR50/70, resolution of soft tissue inflammation, enthesitis and dactylitis, improvement in physical function, skin clearance (IGA score), and general health outcomes (SF-36 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores).

Tuba: Is Janssen assessing Tremfya in H2H comparison with other competitors like Cosentyx, Humira?

Dr. Miller: We are focused on capturing the most useful data for our therapies in PsO and PsA that can help providers understand how treatment can work for patients. In addition to the head-to-head data from the VOYAGE study with adalimumab, we have also conducted ECLIPSE, a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of TREMFYA versus secukinumab in 1,048 patients with moderate to severe PsO. At week 48, numerically greater proportions of patients achieved PASI 90 or PASI 100 and an IGA score of 0 or 0/1 with TREMFYA versus secukinumab, indicating completely clear or almost clear skin. These responses with TREMFYA were seen regardless of baseline age, body weight, body mass index, disease severity, body region, and prior medication, all of which are important to understand, as varying characteristics might affect a patient's response to treatment.

Tuba: Why did Janssen choose to do an H2H study with Humira only? Is there any specific reason?

Dr. Miller: Following our approach to investigate the underlying pathways of immune disease, we are continuing to evaluate TREMFYA as a first-in-class IL-23 inhibitor therapy so that we can work to bring more effective treatments to patients with immune-mediated diseases. In this process, we evaluated TREMFYA against an anti-tumor necrosis factor (TNF)-alpha agent. We will continue to conduct comparative and head-to-head studies to help provide a clear data picture of available options to prescribers and patients.

Tuba: Can you please tell our readers about PASI score? What is it and its significance?

Dr. Miller: The Psoriasis Area Severity Index (PASI) score is a measure of the amount of surface area covered by PsO plaques in each body region, as well as the degree of plaque redness, thickness, and scaliness. It is a way for physicians to assess the severity of a patient's PsO, as well as the efficacy of a treatment in reducing these difficult symptoms. PASI 75/90/100 responses are defined as at least 75/90/100 percent improvement in the PASI score from baseline. Clinicians also use Absolute PASI as a reference for symptom assessment, with the achievement of an absolute PASI score lower than 2 or 3 as a proposed indication of treatment success. A score greater than 5 usually indicates that an alteration of treatment is needed. TREMFYA is the first-in-class IL-23 inhibitor to establish efficacy and safety through five years in PsO, with complete skin clearance rates maintained at five years in a majority of patients.

Tuba: How is Tremfya better than Humira in terms of providing a better quality of life?

Dr. Miller: PsO can have a significant impact on a patient's health-related quality of life (HRQoL). Data from an analysis of VOYAGE 1 presented at EADV demonstrated the correlation between skin clearance and improved HRQoL measures among people living with moderate to severe PsO. The data showed that the Dermatology Life Quality Index (DLQI) response mirrored PASI improvement, with 87.5% of TREMFYA patients with sustained skin clearance (PASI 0 for three years or more) reporting a DLQI score of 0 or 1 after 76 weeks of treatment. Overall, these VOYAGE data show TREMFYA is seen to improve both clinical and QoL scores and to maintain these improvements over time.

Tuba: How does this new data change the market dynamics in PsO & PsA therapy area?

Dr. Miller: TREMFYA is the first and only selective IL-23 inhibitor therapy approved in the U.S. to treat both adults with moderate to severe plaque PsO who are candidates for systemic therapy or phototherapy, as well as adults with active PsA. These data reinforce TREMFYA as a therapeutic option that targets a central disease-driving mechanism of action for patients impacted by PsO and PsA.

Source: Medicine

About Author: Lloyd Miller is the Vice President, Immunodermatology Disease Area Leader at Janssen. He earned his BA in biology at Johns Hopkins University and received his MD and Ph.D. degrees from the State University of New York Downstate Medical Center in Brooklyn. He completed his dermatology residency and post-doctoral research fellowship in the specialty training and advanced research (STAR) program at the University of California Los Angeles

Related Post: PharmaShots Interview: Thermo Fisher Scientific Garret Hampton Shares Insight on the Multiyear Agreement with AstraZeneca for NGS-based CDx