Centessa to Discontinue Development of Lead Asset

 Shares of Centessa Pharmaceuticals fell Thursday after the company announced that it is discontinuing the development of its lead asset, lixivaptan, for autosomal dominant polycystic kidney disease (ADPKD). The decision will end a Phase III and open-label study, the company said.

Boston-based Centessa said the decision to terminate the development of lixivaptan in the ADPKD space was based on a “thorough reassessment of the commercial potential of lixivaptan” as a best-in-class therapy for patients with the disease. Additionally, the company noted “incremental development challenges and associated costs” following the recent observation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in one subject in the open-label Alert study.

Centessa launched in 2021 following the merger of 10 private biotech companies and hit the ground running with a $250 million Series A financing round. One of the companies that combined to form Centessa, Palladio Biosciences, brought lixivaptan into the fold.

Lixivaptan is an oral, non-peptide new chemical agent that works by selectively suppressing the activity of the hormone vasopressin at the V2 receptor. ADPKD is a genetic, progressive disorder characterized by the growth of numerous cysts in the kidneys. The most common symptoms are kidney cysts, pain in the back and the sides and headaches. Other symptoms include liver and pancreatic cysts, urinary tract infections, abnormal heart valves, high blood pressure, kidney stones and brain aneurysms.

Centessa had already begun dosing patients in its pivotal Phase III Action study prior to the discontinuation of lixivaptan. Earlier this year, the company received a key patent in the United States that covers the use of lixivaptan for the treatment of ADPKD. Currently, the only approved medication for ADPKD is Otsuka’s Jynarque (tolvaptan). Jynarque does come with a black box warning as it can cause potentially fatal liver damage. Additionally, liver failure requiring transplantation has been reported in post-marketing studies.

Saurabh Saha, chief executive officer of Centessa, noted that the open-label Alert study was designed to provide an early assessment of lixivaptan’s safety profile in ADPKD patients who were previously treated with Jynarque but developed liver chemistry abnormalities.

“In assessing the recent data from a subject in the Alert Study, we believe that lixivaptan is unlikely to achieve the differentiated safety and tolerability profile Centessa required for further development of the program. Given the revised commercial potential of lixivaptan and our commitment to being financially disciplined, we made the data-driven decision to voluntarily discontinue development of lixivaptan,” Saha said in a statement.

He added that the company hoped lixivaptan would provide patients with ADPKD with a safer alternative to the current treatment regimen.

The discontinuation of the development of lixivaptan for ADPKD is expected to significantly extend the cash runway into 2026, the company noted.

Going forward, Saha said Centessa will continue to advance its innovative rare disease and immuno-oncology programs, and that the hope is to move those programs into the clinic over the next 12 to 24 months.

“With our decision to discontinue development of lixivaptan, we believe we are well-positioned with the capital and resources to execute these programs. We expect a significant reduction in annual cash burn and that our cash runway will now extend into 2026,” he said.

https://www.biospace.com/article/centessa-discontinues-development-of-lead-adpkd-asset-lixivaptan/