Alport’s syndrome is an inherited kidney disease meaning it runs in families and is caused by a genetic mutation. Men are more severely affected than women and it can lead to deafness as well as kidney failure. It was named after a doctor called Cecil Alport who recognized families with the syndrome in 1927.
Swedish biopharma, Calliditas is a company that focuses on developing and commercializing treatments in rare diseases, particularly those with significant unmet diseases. Its randomized double-blind, placebo-controlled study will evaluate small molecule setanaxib in around 20 patients with a genetic diagnosis of Alport syndrome and significant proteinuria despite treatment with a renin-angiotensin system (RAS) blocker.
The treatment will last 24 weeks, and the objective is to evaluate the safety and tolerability of setanaxib in patients with Alport syndrome, as well as the effect of setanaxib on urine protein creatinine ratio (UPCR) and eGFR (estimated glomerular filtration rate) - a measure of how well your kidneys are working - compared to placebo.
Dr Rachel Lennon is professor of nephrology and honorary consultant pediatric nephrologist, at the University of Manchester (UK), and coordinating investigator for the study.
Urgent need in Alport syndrome
She said: “There is an urgent clinical need in Alport syndrome for treatments that delay the progression to kidney failure.
“Alport syndrome can occur as early as the teenage years, when it causes major disruption to learning and education. Clinical trials allow new treatments such as setanaxib to be evaluated for safety and effectiveness in Alport syndrome.”
Setanaxib is also being evaluated in phase 2 studies in squamous cell carcinoma of the head and neck, primary biliary cholangitis, and idiopathic pulmonary fibrosis.
Alport’s syndrome is caused by an abnormality in collagen in the body. Collagen gives parts of the body not supported by bone their shape and strength. There is one particular type of collagen found mostly in the kidney and the ear, and this is affected in Alport’s syndrome, leading to kidney failure and partial deafness.
Women with Alport’s syndrome can produce more normal collagen than men and usually have mild disease. However, they can pass Alport’s syndrome with kidney failure to their sons.
The syndrome can be diagnosed in several ways - if it is known to run in the family, a simple test for blood in the urine may be enough to be fairly sure of the diagnosis. Alternatively, a patient with existing kidney disease might have a kidney biopsy, and as it has a particular appearance in the kidney when examined under the microscope, this is another way it can be identified. Lastly, testing for the abnormal gene in Alport’s syndrome is sometimes possible.
Calliditas Therapeutics is focused on identifying, developing, and commercializing treatments in orphan indications, with an initial focus on renal and hepatic diseases and its lead product, developed under the name Nefecon, has been granted accelerated approval by the US FDA under the trade name Tarpeyo and conditional marketing authorization by the European Commission under the trade name Kinpeygo.
Kinpeygo is being commercialized in the European Union Member States by Calliditas’ partner, STADA Arzneimittel AG.