AstraZeneca had some much needed pipeline success yesterday when it announced positive phase III trial results for naloxegol, a drug used to treat constipation caused by opioid painkillers.
The pharma company now hopes to be able to file for approval of naloxegol in opioid-induced constipation (OIC) in the third quarter of 2013, depending on the outcome of discussions with regulatory agencies in the US and EU.
Naloxegol is designed to selectively block mu opioid receptors in the gastrointestinal tract – preventing constipation – while staying out of the central nervous system so pain relief is unaffected. The drug was licensed by AZ from Nektar Therapeutics in 2009.
In the two pivotal trials (KODIAC-4 and KODIAC-5), naloxegol 12.5mg or 25mg given once-daily was compared to placebo in around 1,200 patients with OIC .
At the higher dose, significantly more patients on AZ and Nektar’s drug met the criteria for an improvement in OIC symptoms in both of the studies. A responder was defined as having at least three spontaneous bowel movements (SBM) per week, with an improvement of least one SBM per week from the start of the trial.
At 12.5mg naloxegol met that endpoint in just one of the trials, but Nektar chief executive Howard Robin said on a conference call that this is not expected to be the dose used clinically, and that the 12.5mg dose was included in the programme not for tolerability considerations but to gauge ” how low we can go and still get efficacy”.
“Opioid-induced constipation is a burdensome condition which is often overlooked, inadequately managed and can negatively impact a patient’s quality of life,” commented Martin Mackay, AZ’s head of R&D.
AZ estimates that up to 35 million patients taking opioids for long-term pain relief will develop constipation and around 50 per cent of OIC suffers do not get relief from current therapies.
Nektar stands to receive milestone payments of $235m on approval and launch of naloxegol in the US and EU, as well as double-digit royalties on sales.
Naloxegol is currently considered a scheduled substance in the US, and AZ has petitioned the Drug Enforcement Administration (DEA) to remove controls based on data it has generated on the abuse potential and dependence-producing properties of the drug.
The positive news comes after a string of pipeline disappointments for AZ, which recently pulled the plug on obesity drug AZD2820 and sepsis candidate CytoFab amid other late-stage failures such as the failure to get US approval for diabetes drug Forxiga (dapagliflozin).