Nektar falls despite positive Phase III data for naloxegol

Nektar Therapeutics (NASDAQ:NKTR) fell $1.11 (14%) to $7.04 on Monday despite reporting positive top-line data from a pair of Phase III trials evaluating naloxegol to treat opioid-induced constipation (OIC) in patients with non-cancer pain. The company disclosed in its 10-Q on Friday that "FDA is exploring whether there is any evidence of a potential cardiovascular class effect related to opioid withdrawal associated with mu opioid antagonists." Naloxegol (formerly NKTR-118) is a PEGylated form of naloxol, a peripheral mu opioid receptor ( OPRM1; MOR) antagonist. Nektar said partner AstraZeneca plc (LSE:AZN; NYSE:AZN) is conducting "comprehensive safety studies" as part of the KODIAC development program. On Monday, the partners reported data from the Phase III KODIAC-04, KODIAC-05 and KODIAC-07 extension of KODIAC-04 showing that there were no "clinically relevant" imbalances in serious adverse events, including major cardiovascular events, between treatment arms.

In the KODIAC-04 trial, once-daily 12.5 and 25 mg oral naloxegol each met the primary endpoint of a greater proportion of OIC responders at week 12 vs. placebo (p=0.015 and p=0.001). In the identical KODIAC-05 trial, high-dose oral naloxegol met the primary endpoint of a greater proportion of OIC responders at week 12 vs. placebo (p=0.021), but low-dose naloxegol missed the endpoint (p=0.202). According to the trial design for both trials, statistical significance for the primary endpoint would be achieved if at least one of the two doses of naloxegol had a p-value of <0.025 compared to placebo. KODIAC-04 enrolled about 650 patients, while KODIAC-05 enrolled about 630 patients. ...