CV fears cloud AstraZeneca's positive results for $1.5B constipation program

Breaking from a long string of trial failures, AstraZeneca ($AZN) offered up positive data from a pair of late-stage Phase III study of naloxegol, an experimental drug for opioid-induced constipation in-licensed from Nektar ($NKTR) in a $1.5 billion deal. The treatment hit its endpoint for both doses in one study while only the high dose cleared that bar in the second study. But Nektar's shares inched up only marginally this morning after an analyst at Jefferies highlighted the FDA's recent move to raise the bar on cardiovascular safety for OIC therapies like this.

Jefferies downgraded Nektar because of the disclosure that Salix ($SLXP) and Progenics ($PGNX) may be required to conduct a lengthy--and expensive--CV study on Relistor, according to Thomson Reuters. And the same fate may await AstraZeneca, which has been struggling to get new drugs up for approval as its flagship products fall to generic competition.

A safety extension study may help highlight a "balanced" safety profile. The most common adverse events seen so far for naloxegol were abdominal pain, diarrhea and nausea. But the most serious adverse event was arthralgia, which occurred only in the high-dose study arm. The 52-week safety study will wrap early next year.

AstraZeneca acquired commercial rights to the drugs back in 2009, when it paid $125 million upfront for NKTR-118 and 119 while promising $1.4 billion in milestones. Then-CEO David Brennan called it a "good example of using externalization to enrich the company's late-stage pipeline."

"Opioid-induced constipation is a burdensome condition which is often overlooked, inadequately managed and can negatively impact a patient's quality of life," said Martin Mackay, the R&D chief at AstraZeneca. "The top-line results of the pivotal KODIAC studies provide important new information on the safety and efficacy of naloxegol as a potential treatment for opioid-induced constipation and we are looking forward to advancing this program."

- here's the release from AstraZeneca
- see the release from Thomson Reuters