Injectable Relistor was approved in 2008 but only for the limited indication of treating opioid-induced constipation in critically ill patients in hospice or palliative care. Relistor use beyond four months was not studied or approved.
In August 2011, Salix and Progenics filed an application with FDA seeking to expand Relistor's label to allow long-term treatment of OIC in all patients with non-cancer pain. The filing included data from a phase III, open-label safety study in which more than 1,000 patients were treated with Relistor for 48 weeks.
In July, FDA rejected Relistor and told Salix and Progenics that additional clinical work would be required before the drug could be approved for OIC. It was at an early October meeting to follow up on the rejection that FDA officials told Salix about the agency's concerns with the cardiovascular safety of the OIC drug class, the company said.
Salix admits that it has not conducted studies of Relistor designed to specifically measure the drug's risk to heart safety. However, data encompassing 4,000 patients treated with Relistor and 1,000 patients taking a placebo has not detected any such signal, said Forbes on Wednesday's conference call.
Forbes added that he's not sure a heart-safety trial of Relistor as requested by FDA is even possible to conduct given the relative paucity of cardiovascular events observed in patients to date. Salix continues to negotiate with the FDA but at this point, Relistor for OIC is in regulatory limbo. Clinical development of a Relistor pill, also for OIC, is also on hold.
Nektar can ill afford any delays in the development of its OIC drug naloxegol. Under a partnership agreement with AstraZeneca, Nektar expects to receive $95 million in cash when naloxegol is submitted for approval in the U.S. and Europe. AstraZeneca will pay Nektar another $140 million if naloxegol is approved and launched commercially.
Whether or not FDA intends to force Nektar and AstraZeneca to conduct another safety study of naloxegol is not clear.
On Friday, Nektar surprised investors with an early filing of its 10-Q for the third-quarter, which included a new risk statement regarding naloxegol:
"For example, we understand that the FDA is exploring whether there is any evidence of a potential cardiovascular class effect related to opioid withdrawal associated with mu-opioid antagonists and naloxegol is a mu-opioid antagonist. Although AstraZeneca is conducting comprehensive safety studies for naloxegol as part of the KODIAC development program, the health authorities retain significant discretion over regulatory requirements which remain very uncertain and difficult to predict prior to obtaining approval."