Guselkumab

Recently, Johnson & Johnson (J&J) announced an agreement with Kaken Pharmaceutical of Japan to acquire the global exclusive rights (excluding Japan) to KP-723, a preclinical STAT6 inhibitor. Under the agreement, J&J will pay $30 million upfront, with potential milestone payments of up to $1.2175 billion, and will receive single-digit to low double-digit percentage royalties on future sales of the drug. Kaken Pharmaceutical plans to initiate Phase 1 clinical trials for atopic dermatitis (AD) next year and intends to explore its application in other Th2-mediated diseases, such as asthma. J&J will be responsible for the global clinical development and commercialization of the drug. The significant investment in STAT6 inhibitors stems from their critical role in the JAK/STAT signaling pathway. STAT6, as a downstream target, primarily responds to the stimulation of cytokines IL-4 and IL-13, promoting the expression of Th2-related genes and enhancing immune responses. In diseases such as asthma and AD, the abnormal activation of STAT6 can exacerbate inflammation and worsen disease progression. STAT6 represents a "first-in-class" target for developing novel oral therapies against these diseases. However, as a transcription factor, STAT6 lacks deep binding pockets, making it challenging to develop drugs against. While early attempts at STAT6 inhibitors for autoimmune diseases often failed due to insufficient affinity, the application of PROTAC technology has provided a promising solution. Currently, the most advanced STAT6 inhibitor project is Kymera Therapeutics' KT-621, whose IND application was approved by the U.S. FDA in October this year. In vitro models have shown that KT-621 can completely block the IL-4/IL-13 pathway by degrading STAT6, with efficacy comparable to or better than the monoclonal antibody Dupilumab. Moreover, KT-621 has demonstrated nearly complete degradation of STAT6 at low oral doses and has shown good tolerability in multiple preclinical toxicity studies. Meanwhile, Sanofi is also actively investing in STAT6 inhibitors to protect its Dupilumab market share. Through partnerships with Nurix and Recludix, Sanofi is developing STAT6 protein degraders and small-molecule inhibitors, both in the preclinical stage. The STAT6 inhibitor space has become a hotspot for heavy investment by multinational pharmaceutical companies in the autoimmune field. According to Frost & Sullivan, the global autoimmune drug market is expected to reach $176 billion by 2030, with a compound annual growth rate of 3.6% from 2022 to 2030. In China, the market size is projected to reach $23.1 billion by 2030, with the share of biologics increasing from 32.9% in 2021 to 71.8% by 2030, making it a major growth driver in the global market. J&J has a rich history and extensive product portfolio in the autoimmune drug space, with flagship products like Remicade (Infliximab), Stelara (Ustekinumab), Tremfya (Guselkumab), and Simponi/Simponi Aria (Golimumab). Despite the declining sales of Remicade due to competition from biosimilars (2023 revenue: $1.839 billion), Stelara's 2023 sales exceeded $10 billion for the first time, reaching $10.858 billion, making it the core pillar of J&J's pharmaceutical business. However, Stelara faces patent expiration, with its U.S. patent expiring in September 2023, leading to a 6.6% revenue decline in Q3 2024 to $2.6 billion. Nevertheless, Tremfya, approved for treating psoriasis, received additional approval on September 11 this year for moderate-to-severe active ulcerative colitis (UC), showing potential to succeed Stelara. To solidify its leadership in the autoimmune field, J&J continues to aggressively pursue new products to replace its existing lineup. In the AD field, J&J has made two acquisitions this year, both targeting bispecific antibodies for AD treatment. It acquired Proteologix for $850 million, securing candidates like PX128 and PX130. PX128, a bispecific antibody targeting IL-13/TSLP, is about to enter Phase 1 clinical development, while PX130, targeting IL-13/IL-22, is in preclinical development for moderate-to-severe AD. J&J also entered an agreement with Numab Therapeutics to acquire Yellow Jersey Therapeutics for approximately $1.25 billion, gaining global rights to NM26, a bispecific antibody targeting IL-4Rα and IL-31 for AD. NM26 is currently in Phase 1 trials and about to enter Phase 2 development. In the psoriasis space, J&J has consistently led the way, offering products like Infliximab, Golimumab, Ustekinumab, and Guselkumab. The recent introduction of Icotrokinra (JNJ-2113), an oral IL-23R-targeting peptide licensed from Protagonist, has achieved positive results in pivotal Phase 3 trials for plaque psoriasis, marking the potential launch of the world's first selective oral IL-23 receptor inhibitor, further cementing J&J’s dominance in this space. Additionally, Nipocalimab, an FcRn-targeting monoclonal antibody acquired for $6.5 billion from Momenta, has shown breakthrough potential across various autoimmune diseases. In August 2023, J&J submitted a BLA to the FDA for treating generalized myasthenia gravis (gMG) and received BTD designation for treating Sjögren's syndrome based on the DAHLIAS Phase 2 study. Nipocalimab is projected to have a peak sales potential exceeding $5 billion, despite existing competition from Argenx and UCB in the FcRn space. As a leader in autoimmune disease therapies, J&J faces challenges such as patent expirations for key products and head-to-head competition from first-in-class rivals. However, its proactive acquisitions and investments reflect its determination to open new pathways in the autoimmune space. Whether J&J can maintain its dominant position in the coming decade remains highly anticipated.

The company seeks approval of TREMFYA to treat plaque psoriasis and active juvenile psoriatic arthritis in children. Credit: marishkaSm/Shutterstock. Johnson & Johnson (J&J) has sought approval for TREMFYA (guselkumab) for paediatric conditions with the submission of two supplemental biologics licence applications (sBLA) to the US Food and Drug Administration (FDA). The applications are intended for the use of the monoclonal antibody to treat paediatric patients aged six years and above with moderate-to-severe plaque psoriasis (PsO), and those five years and older with active juvenile psoriatic arthritis (jPsA). The submission for treating paediatric plaque psoriasis is supported by results from the Phase III PROTOSTAR study in children. It is based on the bridging pharmacokinetic outcomes from the VOYAGE 1 and 2 studies in adults with the same condition. For jPsA, the application utilised pharmacokinetic extrapolation analyses from adult psoriatic arthritis studies, DISCOVER 1 and 2, alongside data from the PROTOSTAR study. Johnson & Johnson innovative medicine immunodermatology disease area leader and vice-president Liza O’Dowd stated: “This milestone underscores our commitment to transform the standard of care for patients of all ages and builds on our expertise and legacy in IL-23 and immune-mediated diseases. “There is a critical gap in the treatment of children and adolescents with these skin and joint conditions, where debilitating symptoms can present challenges related to physical appearance and ability to function. “At Johnson & Johnson, we are working to address this gap by investigating the efficacy and well-characterised safety profile of TREMFYA for paediatric patients.” TREMFYA, which attaches to the p19 subunit of IL-23 and prevents its interaction with the receptor, is already approved for adult indications in the US, including moderate-to-severe plaque psoriasis, active psoriatic arthritis and ulcerative colitis. It is also approved in Canada, Europe and Japan, among other countries, for treating the adult population with moderate-to-severe plaque psoriasis and active psoriatic arthritis. In November 2024, the company sought approval from the US regulator for a new initiation regimen of the antibody in adults with ulcerative colitis .