In continuing coverage from previous editions of Morning Rounds, the Wall Street Journal (2/29, B4, Dooren) reports that on Thursday, the Food and Drug Administration (FDA) "declined to approve a long-acting, injectable form of Eli Lilly & Co.'s top-selling drug Zyprexa (olanzapine), the company said." According to Lilly, "the agency issued a 'not-approvable' letter for the long-acting form of Zyprexa, saying the FDA needed additional information on excessive sedation that occurred in certain patients." The Indianapolis-based drugmaker "is seeking FDA approval of the long-acting form of the drug for use in certain patients with schizophrenia." The FDA "said clinical studies of the drug showed 24 out of 2,045 patients exposed to the long-acting form of Zyprexa suffered from profound sedation after receiving the injection as of Sept. 30, 2007." Furthermore, "earlier this month, Lilly received another report of profound sedation, which was disclosed to the advisory panel," in which "excessive sedation...occurred between three to five hours after injection." Prior to that event, "it was believed that the sedation events occurred within three hours of injection."

        According to the AP (2/29, Murphy), the long-lasting form of the drug "treats adult schizophrenia patients by delivering an injectable dose that can last up to four weeks, as opposed to the once-daily pill currently available for Zyprexa." Some patients "suffering from schizophrenia often have a hard time staying on a daily treatment plan, and may be helped by getting a monthly injection instead," Lilly stated. But, "the drugmaker said about one percent of patients in clinical trials experienced excessive sedation," which "can be marked by a range of symptoms including drowsiness and slurred speech." Indeed, "[s]ome patients also can wind up in a coma-like state, or become unarousable for hours after taking the drug." Researchers at Lilly "have speculated that the condition is caused by doctors incorrectly injecting the drug directly into the bloodstream," where it "is absorbed over a few hours," instead of "into the muscle," where "it dissolves into the body over days and weeks."

        An FDA staff review found that excessive sedation "is a 'serious safety concern' because of its severity and 'relatively high' incidence," Bloomberg (2/29, Lopatto) reports. Currently, the drugmaker "is investing in reformulated products because the original Zyprexa, taken daily, may face generic competition as early as 2011."

        The Indianapolis Star (2/28, Russell) added that the agency's "decision overrules a [unanimous], nonbinding recommendation issued earlier this month by a panel of FDA advisors that the drug should be approved." While the FDA is not required to adopt the recommendations of its advisory panels, it typically does so. Therefore, the non-approvable letter "came as a surprise to many." According to Natexis Bleichroeder analyst Jon LeCroy, "the FDA wants more information about rare cases in which the drug was injected directly into a blood vessel, and went into the blood stream." LeCroy also wrote, "A not-approvable letter typically means a product is dead, but even if approval is still possible, at minimum it implies a significant delay."