Mount Sinai researcher shows novel drug significantly improves signs and symptoms of generalized pustular psoriasis—a rare and life-threatening disease

Journal:   The New England Journal of Medicine

Paper Title:  Trial of Spesolimab for Generalized Pustular Psoriasis

Senior Author: Mark Lebwohl, MD, Dean for Clinical Therapeutics, Professor and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai in New York

Background about the condition:  Generalized pustular psoriasis (GPP) is a rare, life-threatening skin condition for which there are no approved treatments. It is characterized by episodes of widespread eruptions of painful, sterile pustules (blisters of non-infectious pus). There is a high unmet need for treatments that can rapidly and completely resolve the signs and symptoms of GPP flares. Flares greatly affect a person’s quality of life and can lead to hospitalization with serious complications, including heart failure, renal failure, sepsis, and death.

What is the paper about:  A clinical trial showed that spesolimab is a novel, humanized, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogeneses of several autoimmune diseases, including generalized pustula psoriasis. The novel drug demonstrated rapid clearance of pustules in adult patients with generalized pustular psoriasis (GPP) experiencing a flare.

The study met the primary endpoint, 54% of patients had no visible pustules after a single dose of spesolimab, compared to 6% receiving a placebo at week one

Bottom Line:  Spesolimab is rapidly effective in the majority of patients within one week of its first intravenous infusion for patients suffering from generalized pustular psoriasis.

Why the research is important:  Generalized pustular psoriasis is a life-threatening condition that compromises the integrity of the skin.  Patients are frequently hospitalized and often die from sepsis or other complications, including renal failure, high output cardiac failure, and electrolyte balances.

Mark Lebwohl, MD, said about the studyGeneralized pustular psoriasis is a rare life-threatening condition in which the protective functions of the skin are lost, leaving patients vulnerable to loss of electrolytes, nutrients, and fluids for the skin, causing high output cardiac failure, sepsis, and even death.  Until now, other treatments used for this condition have not been reliably effective and are often too slow for a condition that is so dangerous.  Spesolimab will hopefully be the first approved treatment in the United States for generalized pustular psoriasis, and we will finally have a reliable, rapidly effective treatment for this devastating disease. 

Note: FDA has already granted Priority Review, Breakthrough Therapy Designation, and Orphan Drug Designation for spesolimab.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

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