Galderma announced the initiation of two new phase II clinical trials investigating nemolizumab in patients with systemic sclerosis (SSc) and chronic pruritus of unknown origin (CPUO), two chronic conditions with high unmet medical need. The trials represent a significant expansion of the monoclonal antibody's therapeutic applications beyond its current approved indications for moderate-to-severe atopic dermatitis and prurigo nodularis.
Targeting IL-31 Pathway in Autoimmune Disease
Nemolizumab is the first approved monoclonal antibody that specifically targets the IL-31 receptor alpha, inhibiting the signaling of IL-31, a neuroimmune cytokine involved in inflammation and fibrosis. These mechanisms are both hallmarks of systemic sclerosis and drive itch, a key symptom of chronic pruritus of unknown origin.
The systemic sclerosis trial will be a multicenter, randomized, double-blind, placebo-controlled proof-of-concept study investigating the pharmacokinetics and pharmacodynamics of nemolizumab in adults with SSc. Patient enrollment is planned to begin in H2 2025, with completion anticipated in 2028.
"Systemic Sclerosis can have a profound impact on both the quality and length of a person's life. It causes the skin to harden, damages blood vessels, leads to joint pain, and can result in serious fibrosis in multiple internal organs, sometimes with life-threatening consequences," said Professor Oliver Distler, M.D., lead investigator for the systemic sclerosis phase II study in Zürich, Switzerland. "With no currently approved treatments that are indicated to treat the several symptoms this autoimmune disease presents, I look forward to investigating the role that nemolizumab could potentially play in this condition."
Addressing Rare Autoimmune Disease
Systemic sclerosis is a rare, potentially fatal autoimmune disease that causes inflammation and fibrosis (hardening) of the skin and internal organs. It most commonly affects women between the ages of 30 and 50 years old, often leading to a lower quality of life and a much higher risk of death compared to healthy people of the same age. Currently, there are no approved therapies that address the disease as a whole, highlighting the urgent need for effective treatments.
The study was designed in collaboration with a Steering Committee of world-leading rheumatology and dermatology experts, including Professor Dinesh Khanna, M.D., Director of the Scleroderma Program, University of Michigan; Professor Robert Spiera, M.D., Director of the Scleroderma, Vasculitis and Myositis Center, Hospital for Special Surgery, New York; and Professor Johann Gudjonsson, M.D., PhD, Dermatologist, University Hospital Michigan. The trial is expected to be conducted in several countries in North America, Europe and South America.
Exploring Treatment for Chronic Itch
The chronic pruritus of unknown origin trial will be a randomized, double-blind, placebo-controlled proof-of-concept study exploring the pharmacokinetics and pharmacodynamics of nemolizumab in adults. Enrollment is expected to start in H2 2025 in the U.S., with completion anticipated in 2026.
CPUO is an underdiagnosed condition defined as itch lasting for more than six weeks without an identified cause and mostly affects the elderly. The chronic and persistent itch is often described as being as debilitating as chronic pain, leading to reduced quality of life and affecting sleep patterns and mood. There are currently no approved treatments for this condition.
"It is challenging to treat Chronic Pruritus of Unknown Origin as physicians have limited therapeutic options specifically targeting the underlying cause of itch," said Dr. Shawn Kwatra, M.D., PhD, lead investigator and Joseph W. Burnett Endowed Professor, Chairman of Dermatology, University of Maryland School of Medicine. "With the extensive data showing that IL-31 is a key driver of itch, I'm excited to explore whether nemolizumab's inhibition of IL-31 signaling might effectively reduce the intractable itch experienced by patients with Chronic Pruritus of Unknown Origin."
Expanding Therapeutic Portfolio
"Investigating nemolizumab in two new trials in Systemic Sclerosis and Chronic Pruritus of Unknown Origin, both of which are associated with poor patient outcomes and low quality of life, underscores our commitment to addressing skin conditions with high unmet needs," said Baldo Scassellati Sforzolini, M.D., Ph.D., Global Head of R&D at Galderma. "These trials may help us better understand these complex diseases and offer hope for patients seeking relief from these severe and potentially life-threatening conditions."
Nemolizumab was approved in August 2024 by the U.S. Food and Drug Administration for the treatment of adults with prurigo nodularis and in December 2024 for patients 12 years and older with moderate-to-severe atopic dermatitis. The drug is approved for both indications by multiple regulatory authorities worldwide, including in the European Union, Australia, Singapore, Switzerland and the United Kingdom.
The study for chronic pruritus of unknown origin was designed in collaboration with Dr. Sarina Elmariah, MD, PhD, MPH, Associate Professor and Dermatology Director at the Center for Itch and Neurosensory Disorders at the University of California in San Francisco. More information about both studies will be made available on the clinicaltrials.gov website.
