Psoriasis is a chronic inflammatory skin condition affecting millions globally, characterized by patches of red, itchy, and scaly skin known as plaques. This immune-mediated disease can manifest on various body parts, including elbows, knees, scalp, and lower back, causing physical discomfort and sometimes pain. Beyond the physical symptoms, psoriasis can significantly impact an individual’s emotional well-being, leading to feelings of isolation or self-consciousness. It can also increase the risk of associated health conditions, such as psoriatic arthritis.
The development of new medicines involves a multi-stage process, known as the drug pipeline, encompassing all drug candidates under discovery or development. This article explores this journey and highlights innovative new treatments for psoriasis currently under investigation.
Navigating the Psoriasis Drug Pipeline
Preclinical research involves laboratory and animal studies to assess a potential drug’s safety, efficacy, and toxicity. The primary goals are to identify a safe starting dose for human trials and understand potential adverse effects. This initial stage is challenging, with a significant attrition rate.
If a drug candidate proves promising, it progresses to human testing through clinical trials. Phase 1 trials involve a small group of 20 to 100 healthy volunteers or patients to evaluate the drug’s safety, determine a safe dosage range, and identify common side effects. These early studies also assess how the human body absorbs, distributes, metabolizes, and excretes the drug. Most experimental drugs successfully complete this initial phase.
Following Phase 1, Phase 2 trials expand testing to several hundred patients with the target disease, focusing on the drug’s effectiveness and further monitoring its side effects. This phase gathers more detailed information on how the drug performs in a patient population. A portion of drug candidates advance from Phase 2 to the next stage.
Phase 3 trials involve hundreds to several thousand patients across multiple locations. The aim is to confirm the drug’s effectiveness, monitor for less common side effects, and compare its benefits and risks against existing treatments. Successful completion of Phase 3 provides the comprehensive data required for regulatory submission. A smaller percentage of drugs that enter Phase 3 trials proceed to the final regulatory review.
Upon successful completion of all clinical trial phases, the drug sponsor submits an application to regulatory authorities, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), for approval. This submission, known as a New Drug Application (NDA) in the U.S. or a Marketing Authorization Application (MAA) in Europe, undergoes a thorough review process to ensure the drug meets strict safety and efficacy standards. The review process can extend significantly if additional information is requested. The entire drug development process, from discovery to market, is lengthy, with few drug candidates ultimately reaching the market due to stringent requirements and high attrition rates.
Diverse Approaches in Psoriasis Treatment Research
Research into new psoriasis treatments explores a range of therapeutic strategies, moving beyond conventional methods to target the disease through various mechanisms and delivery forms. These diverse approaches aim to offer more effective, convenient, and personalized options for patients. One significant area involves next-generation biologics, complex protein-based drugs derived from living organisms. These therapies build upon existing biologics by exploring new molecular targets or improving drug delivery to enhance efficacy and reduce treatment burden.
Another promising category includes small molecule oral therapies. Unlike biologics, these are chemically synthesized compounds taken as pills, offering a convenient alternative to injectable treatments. These small molecules target specific pathways inside cells that contribute to inflammatory processes in psoriasis. Their oral administration can improve patient adherence and accessibility.
Novel topical treatments represent another important area of innovation, focusing on new creams, gels, or foams applied directly to the skin. These advanced formulations often incorporate active ingredients with new mechanisms of action, aiming for better penetration and localized effects. They also minimize systemic side effects. Such treatments are particularly beneficial for patients with milder forms of psoriasis or those seeking to complement systemic therapies.
Beyond these, emerging therapies investigate more experimental approaches, such as gene therapies or cell-based treatments. While still in early developmental stages, these modalities aim to address underlying genetic or cellular dysfunctions that contribute to psoriasis. These highly specialized treatments could potentially offer long-term or even curative solutions for a subset of patients.
Notable Advances in Psoriasis Drug Development
Recent breakthroughs in understanding specific inflammatory pathways in psoriasis have led to highly targeted therapies. These advancements focus on interrupting the immune processes that drive the disease, offering improved efficacy and new administration options. Among the most impactful developments are novel inhibitors of specific interleukins, which are signaling proteins in the immune system.
Targeting interleukin-17 (IL-17) has yielded several effective treatments. These inhibitors block either the IL-17A protein or its receptor, disrupting a key pathway in psoriasis pathogenesis. Bimekizumab, for instance, blocks both IL-17A and IL-17F, demonstrating superior efficacy and faster onset of action compared to agents targeting IL-17A alone. Other established IL-17 inhibitors like secukinumab, ixekizumab, and brodalumab also offer rapid and robust responses for patients with moderate to severe psoriasis.
Similarly, interleukin-23 (IL-23) inhibitors represent a significant advance, targeting an upstream cytokine central to the inflammatory cascade. Risankizumab, guselkumab, and tildrakizumab are examples of these biologics, specifically targeting the p19 subunit of IL-23. These therapies have shown superior efficacy in clearing skin lesions compared to some older biologic treatments. An oral IL-23 receptor antagonist peptide, JNJ-2113, is also in development, showing promise for achieving biologic-level activity through a convenient oral form.
Research is also exploring newer cytokine targets, such as interleukin-21 (IL-21). This cytokine plays a role in the differentiation of T helper 17 (Th17) cells, central to psoriasis development. Inhibitors of IL-21 are being investigated, holding potential for patients who may not respond adequately to existing IL-17 or IL-23 inhibitors. This broadens the therapeutic landscape, offering alternative mechanisms for managing the disease.
Another area of innovation involves Tyrosine Kinase 2 (TYK2) inhibitors, which are oral small molecules. TYK2 is a member of the Janus kinase (JAK) family and mediates several cytokine pathways, including those involving IL-23 and subsequent IL-17 production. Deucravacitinib (Sotyktu) is an FDA-approved TYK2 inhibitor that works by allosterically blocking TYK2, providing an oral option for moderate to severe plaque psoriasis. Its once-daily oral dosing and favorable safety profile often avoid the need for routine laboratory monitoring, representing a significant advantage for patient convenience.
The broader class of JAK inhibitors also continues to evolve. These oral medications block the JAK-STAT signaling pathway, inhibiting the production of various proinflammatory cytokines. While some JAK inhibitors, like tofacitinib, are approved for related conditions like psoriatic arthritis, newer, more selective JAK inhibitors are emerging. The advantage of oral administration combined with strong efficacy profiles makes these treatments attractive options, particularly for patients seeking alternatives to injectable biologics.
Additional novel targets are under investigation, including inhibitors of IL-1 alpha/beta or IL-36, and new phosphodiesterase-4 (PDE4) inhibitors. Researchers are also exploring compounds that target the aryl hydrocarbon receptor (AHR) pathway, such as topical tapinarof, offering steroid-free options for direct skin application.