The European Medicines Agency (EMA) has accepted the Marketing Authorisation Application (MAA) for AstraZeneca's naloxegol, an investigational peripherally-acting mu-opioid receptor antagonist, which is designed for the treatment of opioid-induced constipation (OIC) for adult patients 18 years and older, including patients with inadequate response to laxatives.

The MAA filing was based on comprehensive data from the core phase III KODIAC programme, comprised of four clinical trials designed to investigate the safety and efficacy of naloxegol for the treatment of OIC. Two pivotal phase III studies, KODIAC-04 (n=652) and KODIAC-05 (n=700), both 12-week, multicentre, randomised, double blind, placebo-controlled trials, evaluated 12.5 mg and 25 mg doses of naloxegol administered once-daily. KODIAC-07 was a 12-week safety extension of KODIAC-04, and KODIAC-08 (n= 534) was an open-label, randomised, 52-week, long-term safety trial.

Naloxegol has the potential to be the first once-daily oral peripherally-acting mu-opioid receptor antagonist medication for patients with OIC. Naloxegol was developed using Nektar’s oral small molecule polymer conjugate technology.

Naloxegol is covered by the exclusive worldwide license agreement announced on September 21, 2009 between AstraZeneca and Nektar Therapeutics. Under the terms of the recently amended license agreement, AstraZeneca will make a $25 million milestone payment to Nektar within five business days of acceptance of the MAA by the EMA.

OIC is a condition caused by prescription opioid pain medicines. Opioids bind to specific proteins called opioid receptors. When the opioids bind to certain opioid receptors in the gastrointestinal (GI) tract, constipation may occur. Opioid-induced constipation is a result of increased fluid absorption and lower GI motility due to opioid receptor binding in the gastrointestinal tract.

Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms. In the area of pain, Nektar has an exclusive worldwide license agreement with AstraZeneca for naloxegol (NKTR-118), an investigational drug candidate, which has completed Phase 3 development as a once- daily, oral tablet for the treatment of opioid-induced constipation. This agreement also includes NKTR-119, an earlier stage development program that is a co-formulation of naloxegol and an opioid. NKTR-181, a novel mu-opioid analgesic candidate for chronic pain conditions, is in phase II development in osteoarthritis patients with chronic knee pain.

NKTR-192, a novel mu-opioid analgesic in development to treat acute pain is in phase I clinical development. In oncology, etirinotecan pegol (NKTR-102) is being evaluated in a phase III clinical study (the BEACON study) for the treatment of metastatic breast cancer and is also in phase II studies for the treatment of ovarian and colorectal cancers. In anti-infectives, Amikacin Inhale is in phase III studies conducted by Bayer Healthcare to treat patients with Gram-negative pneumonia.

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases.