AstraZeneca should not have to carry out a cardiovascular outcomes study prior to approval of its opioid-induced constipation (OIC) drug Movantik, according to an FDA advisory committee.
The decision by the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) covers all drugs in the peripherally-acting mu-opioid receptor antagonist (PAMORA) class of drugs, but it was only narrowly passed.
Of the 24 panellists, 12 said there should be no requirement, while seven voted for trials and five said they should be carried out for certain products.
Assuming the FDA follows the panel’s advice, Movantik (naloxegol) is now facing one less obstacle to regulatory approval in the US, where the FDA is scheduled to deliver a verdict on the drug’s marketing application by 16 September. However, AZ will likely have to provide post-marketing data on Movantik’s cardiovascular safety.
Movantik is a pegylated form of naloxol that 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.
Concern about the safety of the PAMORA class – which also includes Cubist Pharma’s Entereg (alvimopan) and Salix’ Relistor (methylnaltrexone) – emerged after one of phase III trials conducted with Entereg showed a greater rate of heart attack for the drug compared to placebo.
The finding did not stop the FDA approving Entereg (originally developed by Adolor and GlaxoSmithKline) for short-term treatment of OIC in 2008, with certain restrictions, but it raised the regulatory bar for follow-on PAMORAs.
“We are pleased that the committee did not find it necessary to require a cardiovascular outcomes trial for the PAMORA class,” said AZ’s chief medical officer Briggs Morrison. “We look forward to … the potential to provide patients with chronic non-cancer pain affected by OIC with an additional treatment option.”
The news is even better for Nektar, which financially has a lot more tied to the project. Under the terms of a revised agreement with AZ signed last August, the drug delivery specialist stands to receive a $35m milestone – on top of $70m received after the FDA accepted the regulatory filing – provided no cardiovascular study is required.
The two companies also agreed a clause in the revised contract that would allow AZ to hand back rights to the drug – and be repaid the $70m milestone plus interest – if a cardiovascular study is mandated.
If approved, Movantik would be the first once-daily, oral PAMORA for the treatment of OIC in patients with chronic non-cancer pain in the US. It is also under regulatory review in Europe and Canada and has been tipped by some analysts to become a $350m-a-year product at peak, while others predict it could go as high as $1bn given the high incidence of OIC in patients taking opioids.