The US Food and Drug Administration (FDA) has followed the advice of its advisory committee and declined to approve Otsuka Pharmaceutical's tolvaptan as a treatment for patients with polycystic kidney disease (PKD).
Otsuka has been trying to extend the indications of tolvaptan to include the treatment of adult patients with rapidly progressing autosomal dominant PKD, a rare and life-threatening disease that can cause irreversible kidney damage.
However, the FDA sent a complete response letter to the company indicating that it "cannot approve the application in its present form" and requesting "additional information", said the pharma company in a statement.
It follows a recommendation from the agency's Cardiovascular and Renal Drugs Advisory Committee, which voted nine to six not to approve tolvaptan based on current evidence.
The drug is a first-in-class vasopressin V2-receptor antagonist designed to inhibit the formation, proliferation and growth of cysts that characterise ADPKD, which affects around 120,000 adults in the US and is the fourth most common cause of end-stage renal disease (ESRD). The FDA granted the drug a priority review in this indication because there is a lack of effective therapies for ADPKD.
Tolvaptan is already approved in the US under the Samsca brand name for the treatment of low blood levels of sodium (hyponatraemia), which can be caused by conditions such as organ failure and pneumonia.
However, the FDA ruled earlier this year that it should not be used for longer than 30 days or in patients with underlying liver disease due to possible liver injury leading to organ transplant or death.
Samsca is sold in 14 countries and has been growing fast, with fiscal first quarter sales up 90 per cent year-on-year to 4.5 billion yen ($46m), with the franchise recently expanded by a new low-dose formulation (7.5mg) intended for use in elderly patients that was launched in Japan in June.
Otsuka is looking to ADPKD to lend additional momentum to tolvaptan's growth trajectory and filed for approval in this setting in Japan in May. The drug is also in phase III testing as a treatment for oedema in cardiac patients and in phase II for oedema in cancer patients.
"Otsuka is evaluating the content of the FDA's response and will work closely with the agency to determine if there are viable paths forward to address its outstanding questions," said Robert McQuade, Otsuka's chief strategic officer.