Alumis's ONWARD Program: A Promising Step Forward in Psoriasis Treatment
Psoriasis is a chronic autoimmune disease affecting millions worldwide, characterized by raised, red, scaly patches on the skin. These patches, often itchy and painful, can significantly impact a person's quality of life, both physically and emotionally. Moderate-to-severe plaque psoriasis, the most common form of the disease, presents a significant challenge for patients and healthcare providers alike. Recent advancements in targeted therapies have offered new hope for individuals living with this condition, and among these, the development and clinical trials of novel drugs like ESK-001 by Alumis represent a significant stride forward.
Alumis, a biopharmaceutical company dedicated to developing innovative treatments for immune-mediated diseases, has recently announced the completion of patient enrollment in its pivotal Phase III ONWARD program. This program aims to evaluate the safety and efficacy of ESK-001, an oral tyrosine kinase 2 (TYK2) inhibitor, for treating adults with moderate-to-severe plaque psoriasis. The ONWARD program comprises two global, parallel Phase III trials, ONWARD1 and ONWARD2, and an optional long-term extension trial, ONWARD3. The culmination of patient enrollment in these trials marks a critical milestone in the ongoing quest for more effective psoriasis treatments.
The ONWARD1 and ONWARD2 trials are placebo-controlled, randomized, double-blind, 24-week, multi-center studies. More than 1,700 subjects have been enrolled, reflecting the extensive scale and rigor of the program. Participants were randomized into a 2:1:1 ratio, receiving either 40mg of ESK-001 twice daily, a placebo, or apremilast, an existing oral therapy for psoriasis. This randomization approach allows for a robust comparative analysis, crucial in determining the true efficacy and safety profile of ESK-001.
The co-primary efficacy endpoints of these trials are significant clinical measures: the proportion of subjects achieving a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) and a score of 0/1 on the static Physician's Global Assessment (sPGA) at week 16. PASI 75 is a widely recognized benchmark for assessing the improvement in psoriasis severity, while sPGA provides a clinical assessment of the overall disease state. Achieving these endpoints would signify a substantial therapeutic benefit for patients. Following the initial 24-week period, subjects have the option to join the ONWARD3 trial, designed to assess the treatment's durability and long-term safety, essential for understanding the long-term implications of ESK-001 use.
Martin Babler, CEO and President of Alumis, expressed enthusiasm about the completion of patient enrollment. He highlighted the dedication of patients, investigators, and the Alumis team in achieving this milestone. With over 1,700 patients enrolled across the two trials, the sheer scale of the ONWARD program underscores the urgency and importance of developing more effective psoriasis treatments. Babler also noted that the company is on track to report topline results in early Q1 2026, which would bring them closer to delivering potentially transformative treatment solutions for patients in need.
The development of ESK-001 is supported by positive data from the Phase II STRIDE trial and an ongoing open-label extension. These earlier trials provide a foundation of evidence suggesting that ESK-001 is both effective and generally well-tolerated. Furthermore, Alumis is actively developing a once-a-day, modified-release oral formulation of ESK-001 to replace the current immediate-release formulation. This improvement in formulation could significantly enhance patient adherence and convenience, further bolstering the potential impact of ESK-001.
Beyond plaque psoriasis, Alumis is investigating ESK-001 in other immune-mediated conditions. The Phase IIb LUMUS trial is evaluating ESK-001 for systemic lupus erythematosus, a chronic autoimmune disease that can affect multiple organs. This expansion of ESK-001’s potential therapeutic range demonstrates Alumis’s commitment to addressing a wider spectrum of autoimmune diseases. The company’s use of a precision data analytics platform to explore ESK-001 in other immune-mediated conditions further highlights its innovative approach to drug development.
Last December, Alumis reported positive outcomes from a Phase I trial of another selective TYK2 inhibitor, A-005, in healthy subjects. This ongoing exploration of TYK2 inhibition underscores the potential of this therapeutic class in treating various immune-mediated diseases. TYK2 inhibitors work by targeting a specific enzyme involved in the inflammatory pathways that drive psoriasis and other autoimmune conditions. By selectively inhibiting TYK2, these drugs aim to modulate the immune system and reduce inflammation without causing broad immunosuppression, a common issue with older, less targeted therapies.
The significance of Alumis's ONWARD program cannot be overstated. For individuals living with moderate-to-severe plaque psoriasis, effective treatments can mean the difference between a life limited by their condition and one where they can fully engage in their daily activities and enjoy a higher quality of life. Current treatments, while helpful, do not work for everyone, and some come with significant side effects. The potential for a new, oral therapy like ESK-001 to offer significant relief with a manageable side effect profile is tremendously exciting.
The rigorous nature of the ONWARD trials, including the large sample size, placebo and active comparator arms, and clearly defined endpoints, will provide high-quality data on ESK-001’s effectiveness and safety. If the results are positive, ESK-001 could become a valuable addition to the treatment arsenal for psoriasis, offering patients and clinicians another option for managing this challenging condition. The development of a modified-release formulation further enhances its potential, making treatment more convenient and potentially improving adherence.
In conclusion, Alumis's completion of patient enrollment in the Phase III ONWARD program is a significant milestone in the development of ESK-001 as a potential treatment for moderate-to-severe plaque psoriasis. With robust clinical trials underway and promising data from earlier phases, there is reason for optimism. The potential for a new, oral therapy that effectively manages psoriasis with minimal side effects could profoundly impact the lives of many individuals. As the biopharmaceutical industry continues to innovate, the hope for more effective, targeted therapies grows, offering renewed hope and a brighter future for those living with chronic immune-mediated diseases like psoriasis.
List of 5 Psoriasis Researchers:
Dr. Alan Menter: A leading dermatologist and psoriasis researcher known for his extensive work in clinical trials and treatment guidelines.
Dr. Kristina Callis Duffin: A dermatologist and researcher focusing on psoriasis genetics, comorbidities, and quality of life.
Dr. James Krueger: A prominent figure in psoriasis research, particularly in understanding the immunopathogenesis of the disease.
Dr. Mark Lebwohl: A renowned dermatologist and researcher specializing in psoriasis, eczema, and other skin conditions.
Dr. Alice Gottlieb: A leading dermatologist known for her research on the immunologic mechanisms of psoriasis and the development of biologic therapies.
