Bayer takes Alport syndrome drug into phase 2
Bayer has started a phase 2a trial of an antibody that it hopes could provide a targeted, potentially disease-modifying therapy for Alport syndrome, a rare, genetic disease that leads to chronic kidney disease (CKD).
Alport is caused by mutations in genes that are involved in the formation of type IV collagen, a protein integral to the structure of organs and tissues, and is the second most common form of inherited kidney disease.
Along with progressive kidney damage, which can sometimes result in patients needing a kidney transplant in early adulthood, it also leads to hearing loss and eye abnormalities affecting vision. The kidneys soon lose their ability to remove waste products from the body properly, resulting in end-stage kidney disease.
Current treatment for Alport is based on drugs that are designed to reduce the workload of the kidneys – ACE inhibitors and angiotensin receptor blockers (ARBs) – and slow down disease progression. Despite the use of those drugs, patients still experience progressive decline of kidney function, resulting in end-stage kidney disease in their 30s or even earlier.
Bayer's new antibody – codenamed BAY 3401016 and stemming from an alliance with Evotec – is designed to block a protein called Semaphorin 3A (Sema3A), which is thought to be involved in the progression of kidney damage in Alport.
The drugmaker hopes to show in the new ASSESS study that BAY 3401016 can reduce proteinuria – protein in the urine that is a marker for kidney disease – and slow down the loss of kidney function. It will compare a weekly dose of the antibody over 24 weeks to placebo, with the main efficacy measure being the change in urinary albumin creatinine ratio (UACR) from baseline.
"The initiation of the ASSESS trial represents an important milestone for our investigational BAY 3401016 programme," said Andrea Haegebarth, global head of research and early development for cardiovascular, renal, and immunology at Bayer's pharma division.
Other drugs that have been tested for Alport include Bayer's mineralocorticoid receptor (MR) antagonist Kerendia (finerenone), Novartis' endothelin A receptor antagonist Vanrafia (atrasentan), and Eloxx Pharma's gene therapy ELX-02. Bayer does not seem to have an active trial of Kerendia in Alport at the moment, however, and ELX-02's progress seems to have been scuppered by the company running out of money.
