Throughout the morning session, it appeared like a typical FDA meeting, according to people in the audience like Walsh—a dispassionate scientific discussion, lots of data and graphs, the typical back and forth, but no hint of a brewing insurrection. Zogenix had conducted two clinical trials of Zohydro to test the drug’s effectiveness and safety, and there was some polite disagreement about the results. One trial started out with more than 500 patients with lower-back pain (one-third dropped out before its completion), but when the company scientists analyzed the numbers, they concluded that the drug provided a statistically significant improvement in pain relief—0.5 points better pain relief on a subjective, 11-point scale—compared with a sugar pill. An outside expert, Judith Kramer of the Duke University School of Medicine, burrowed into the company data, however, and pointed out that the placebo effect was enormous—54 percent of people taking Zohydro claimed to be satisfied by the relief of chronic pain at the end of one study, she noted, but so did 35 percent of people receiving a sugar pill, and in general the pain patients felt worse after three months of treatment than when they began—just not quite a bad as the patients on placebo. Zogenix medical director James Breitmeyer called the results “robust and clinically significant”; one of the outside advisers described the effectiveness as “modest at best.” The company also outlined an elaborate “safe use” program to educate physicians, monitor prescriptions, and minimize abuse of the drug; many committee members remained unconvinced the safeguards would work.
But the first significant departure from the usual FDA proceedings occurred during a midday session, when members of the advisory committee passed around a Kleenex box to dry their eyes as they listened to public testimony from ordinary citizens. The FDA typically reserves some time for patient-advocacy groups that want the agency to approve a drug; this time, many of the speakers described how painkillers had destroyed their lives.
Avi Israel, of Buffalo, chronicled how his 20-year-old son, Michael, developed a “medically sanctioned addiction” to hydrocodone, which was prescribed for his Crohn’s disease. “On the morning of June 4, 2011, after being refused help by his counselor, Michael locked himself in my bedroom, put a shotgun under his chin, and pulled the trigger,” Israel said. Cheryl Placek, also of Buffalo, described the “worst day” of her life, when her 28-year-old son, Daniel, a Navy veteran with chronic back pain who had become addicted to hydrocodone and begun to deteriorate psychologically, eventually hanged himself at the Veterans Affairs hospital in Buffalo in January 2012; if Zohydro was approved, she told the FDA, “you are basically inviting people to take their own lives, or it will end their lives.” Daniel Busch, a psychiatrist at Northwestern University’s Feinberg School of Medicine, described how addiction to prescription painkillers led to the death of his son, Joshua, a college student; “I’m disturbed the FDA is even hearing the new drug application for Zohydro,” he said. Pete Jackson, the head of a citizens’ group opposed to the overprescribing of opioids, described the death of his 18-year-old daughter, Emily, who overdosed on a single OxyContin pill. (There were many ordinary citizens lobbying for Zohydro, too, with equally heart-rending stories about life with chronic pain. But almost all of their stories began, “Zogenix has paid for my travel today.”)
The most dramatic moment of these hearings often happens when the panel debates, and votes on, the merits of a new drug. And the simple explanation for how the FDA wound up approving a high-dose, non-tamper-resistant version of a highly addictive narcotic came out in that final discussion and boiled down to a single philosophical question: What is more important, adhering to an equitable regulatory framework for drug approval (and maintaining what the FDA called “a level playing field” for the company) or considering the larger issue of public health?
The neutral tone of the early part of the meeting began to break down, and one of the triggers was when Sharon Walsh was asked to clarify her research. Zogenix representatives then attempted to portray her results on the abuse potential of hydrocodone as part of a “cloud of misunderstanding” and challenged her suggestion that Zohydro could be another OxyContin. Panel members took note of the way Walsh rebuffed these efforts (“Stalwart,” one doctor later called it), and she noticed that the advisory committee became more skeptical about the drug, its questions more pointed. “I could just feel and hear from the questions that were coming from the committee that there was some surge,” says Walsh. “Opinions were beginning to harden. And I think that the company felt that shift.”