AstraZeneca (AZ) took a step closer to securing US approval for its new candidate for opioid drug-induced constipation (OIC) after the US Food and Drug Administration (FDA) started the clock ticking on its review of the drug.
Naloxegol – a pegylated form of opioid antagonist naloxol licensed from US firm Nektar Therapeutics – could become the first once-daily drug in its class for OIC in the US, setting it up to compete with Sucampo and Takeda’s twice-daily Amitiza (lubiprostone).
It is estimated that around 35 million patients taking opioids for long-term pain relief develop constipation, with 40 to 50 per cent failing to get relief from current therapies. This has led to peak sales estimates of $350m or more per year at peak, while some analysts suggest even $1bn-plus is feasible.
Sucampo reported Amitiza sales of a little over $80m in 2012 but that product is also tipped to reach $200m.
In two phase III trials, the highest dose of naloxegol tested (25mg) achieved significant increases in spontaneous bowel movement frequency compared to placebo, although a lower 12.5mg dose achieved that objective in only one of the pivotal studies.
There were few cardiovascular side effects reported – which could be significant as the FDA raised concerns about heart effects in patients who use opioids for chronic pain alongside OIC drugs on a long-term basis.
The acceptance of the marketing application by the FDA sparks a $70m milestone payment to Nektar. The biotech also stands to get an additional $140m in milestone payments upon approval and launch in the US and EU. An FDA advisory panel has been tentatively scheduled for March 10-11, 2014.
Naloxegol was the first oral drug designed using Nektar’s polymer conjugate technology and has been engineered to stay out of the central nervous system (CNS) to preserve the painkilling effects of the opioids, while antagonising the mu-opioid receptors in the gut to reverse the constipating side effect.