The Antidote: Inside the World of New Pharma (49 page)

Thomson had a history of avoiding corporate celebrations, but now, at fifty-three, he had other frustrations just as urgent as when he was a self-described “protein jock” spending long nights in the cold-room on the company’s first project. What he’d signed on to do at Vertex was to build a sustainable organization: a church, so to speak, built on Boger’s vision. “I said, ‘I hear you’re starting a company,” he would recall telling Boger. “ ‘Is it all theoretical, or do you need some scientists?’ ” Vertex had two breakthrough drugs and a standout pipeline, but when Thomson looked beyond the rest of the decade—to where the blockbusters of the 2020s would come from, and how a global Vertex would become the hub of a larger network of interests—he worried that the company was unprepared and too cautious. He especially worried that it was moving too slowly in China and the Pacific Rim.

Vertex planned to celebrate the launch by bringing together the entire company for an extravaganza in the fall. Emmens wanted a timely, smaller party to reward the Cambridge site. The next Wednesday after work, eight hundred Vertex employees poured into the ballroom of the Hyatt Regency. Confetti cannons stood ready in the corners as the crowd drifted among the bars and food stations. Emmens spoke first, discussing the significance of Incivek to the company.

“We’re not just launching a drug,” he said. “We’re really showing the world what Vertex is, and who we are, not only what we’re doing now but what we’re gonna do in the future. It’s a big deal. We’re here to become sustainable. That’s when we have income that covers our expenses, which are now $3.2 million a day.” He was quickly becoming admired in the company for his brisk yet thoughtful confidence and understated defiance. With reporters, he had compared Vertex’s battle with Merck to David versus Goliath. Now there were two Goliaths. Emmens retold the biblical story, reassuring the crowd that size didn’t matter—indeed, that
they were more agile, more emotionally engaged, better positioned than the Philistines and their legions.

“David believed and was very good at what he did. He took one stone, and he hit Goliath in the head—well, he also cut his head off. So we’re out there now slinging our stones. They’re big and scary, but we’re very good at what we do, and very focused.”

Patient activist Kelly Ann Mann-Hester, who spoke so compellingly at the AdComm, nervously walked onstage and took the microphone from Wysenski, who had invited her. Mann-Hester had watched her husband die of hepatitis C in the 1990s and was a mother of four and a grandmother of five. She reprised her story of personal transformation, from living to die to learning how to live
until
she died. “I’d tried everything,” she recounted. “When I began Incivek, I believed I was doing it for altruistic reasons. I honestly thought, ‘I’m not gonna get cured. I’ve had seven treatments. It won’t be me. Maybe they’ll learn enough from me to help save somebody else.’ ”

Since being cured in 2010, Mann-Hester had made her mission “testing and treatment.” It didn’t matter if there were new cures for hepatitis C if you didn’t know you were infected, like the estimated three million Americans and hundreds of millions around the world who remained in the dark about their diseased livers. She improvised a group experiment to demonstrate. “Raise your hand,” she said, “if you have had a tattoo or a body piercing; if you’ve ever used IV drugs or if you’ve ever shared a needle with somebody or got stuck with a needle by accident, especially if you were a health care worker before 1990; if you had a transfusion or dialysis, or were born from someone who had a transfusion.”

Several dozen people raised their hands, but hesitantly, looking around. Even here, announcing you might be infected with HCV posed risks.

“Now out of those hands, how many of you have been tested for hepatitis C?” she asked.

Only a few hands went up, a minor fraction. Mann-Hester seized on the troubling disparity. “That’s my point, that’s why I’m here. I’m doing this for that reason. Education starts at home. Test yourself. Treat yourself. Find out you’re good to go so that this company can be good to go
further. We have to remove the stigma from hepatitis C because that’s one of the reasons that keeps people from getting tested, and there’s no reason for it anymore. I’m living proof. I’m standing here as someone who was cured by Incivek, so I know. I want you to own your future, and I want you to help people own their future.”

The last speaker was Boger. Looking over the milling crowd, recognizing only about half of them, he began, “Hi, everybody, I’m Joshua Boger, unemployed person.” Most new hires didn’t get the joke, but they laughed alongside the veterans. Boger was the founder who officially stepped down two years ago but was still a director. The painful circumstances of his departure had mostly healed with the realization that Emmens went out of his way to credit Boger wherever and whenever possible while also successfully sticking to first principles. None of the torchbearers had put out his or her torch. The culture seemed to be holding despite his prior apprehensions. In Emmens’s speeches, internal and external, Vertex remained “Josh’s dream.”

As Boger had told the field force by satellite during Launch Week, the most common question he heard now from well-wishers was: Did you think this would ever happen? “This is exactly what I thought would happen,” he said. “But I also thought it would take an enormous amount of effort and an enormous number of talented people. And there wasn’t any reasonable expectation that those people would come together to do that.

“Bringing a major drug forward, bringing it out of discovery and into development, then out of development and into the market, bringing it to patients and changing their lives, is . . .
the hardest thing that humans do
,” Boger said. “Putting a man on the moon? Not . . . so . . . hard. Engineering is an amazing discipline, but it’s also a discipline that succumbs every single solitary time to time and effort. If you give me twenty years and a half trillion dollars, I guarantee I can put people on Mars and bring them back. I guarantee it. Any of you could guarantee it. But making a new drug that changes people’s lives is almost beyond human understanding.

“So the second question I get often is, ‘So, what’s next?’ ‘You cannot imagine what’s next’ is what my answer is. You don’t create an organization
like this, fall over the finish line, even with a success as big as Incivek, and say, ‘I’m done now, this is it.’ ”

Whatever the company’s desire to downplay its earlier brashness, Boger felt that now, more than ever, was the time to act and sound bold, both to inspire and intimidate. Was designing and developing and bringing to patients a life-altering medicine—not a cancer “breakthrough” that extended life expectancy in trials by a few months, a drug that cost too much and did too little, but a novel compound that actually saved a life or restored a quality of living that had seemed beyond dreaming about—the hardest thing that humans do? Maybe not. But it was impossible for any of them to name anything harder. Who, at such a moment, would want to try? They burst into thunderous applause. A blizzard of confetti exploded from the corners. Boger, to borrow a famous trope from
Jerry Maguire
, a film about a high-powered sports agent who crafts the ultimate living room pitch to win over a woman who already has succumbed to his fervent mission and charm, had them at “Hi.”

JUNE 6, 2011

At ten o’clock on Monday morning, Ken sailed into the small conference room and took his seat at the head of the table. At the opposite end, poring over his PowerPoint with Smith, was Dr. Christopher Wright, vice president for clinical development. With Kauffman on the road promoting Incivek, Wright was fast being groomed to become Vertex’s top clinician. A neuroscientist by training, he was another defector from the world of Harvard medical research, a muscular MD-PhD in his early forties who sported a modest Afro, long sideburns, and fashionable designer glasses.

The protocol before the disclosure committee was a twenty-patient, Phase II, double-blinded, multidose study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of the corrector VX-809 alone and in combination with VX-770 in CF patients with two copies of the delta-F508 defect. In other words: the first preliminary data from a tiny cohort on whether combination therapy could do for the great majority of people with CF what VX-770 alone was doing for the small G551D genotype.

Mueller and Wysenski huddled on one side of the table; on the other, Partridge, Olson, Megan Pace, and Dawn Kalmar, who had joined Vertex from Genentech as a product spokeswoman and who would compose the press release. Anticipation was appropriately high. Failure or ambiguous results in this study would represent a serious reversal, since Vertex had already showed that VX-809 by itself offered no improvement.
The hope now was that VX-809 would repair a significant portion of misfolded CFTR and get it to the surface, where VX-770 would then hold open the channels long enough to substantially increase the flow of salt and water across the membrane, lubricating the airways and other affected tissues.

“We’re currently scheduled for a premarket release Thursday,” Ken began, putting the team on notice that within the next three days Vertex would have to decide not only what the study had revealed, but, more to the point, what the company could safely conclude from it and accurately say about it.

Wright summarized the top-line data, reading from his laptop as the others followed along. Well tolerated, the cocktail produced no unexpected safety findings—always welcome news, since the safer the regimen, the more dosages can be increased. The primary end point of the study was to observe a drop in sweat chloride. When VX-809 was first given to patients as monotherapy, there was a significant drop relative to baseline; when VX-770 was added for seven days, Wright said, there was a further reduction consistent with Vertex’s theory that you could double the electrophysiological effect. Clearly the molecules were synergistic. In 20 percent of subjects—two patients—the combined effect was profound, sweat chloride dropping steeply.

Although not on the same order of potency as the Vertex swoosh or the other company-altering “envelopes,” Wright’s presentation unambiguously proved the concept. The company didn’t know if the combined effects of the drugs could relieve lung disease—the FEV1 data after the one week that the subjects were taking both drugs were scant and inconsistent—but the study provided ample promise for moving ahead, with the potential to increase dosages to gain more potency. The mood of the group was decidedly upbeat but sober: excitement marbled with caution and relief.

Smith zeroed in on the super-responders. He did a quick extrapolation, envisioning the shape of the curve. If combination therapy could dramatically boost CFTR function in even 20 percent of those sixty thousand patients worldwide with at least one copy of the delta-F508 mutation, about twelve thousand more patients might benefit from
Vertex’s cocktail. “If you can take this from three thousand to fifteen thousand, that would be huge,” he suggested, brightly. Mueller, seated next to him, chafed. He reminded Smith that the study was far too small to validate any such estimate. “I would keep it as simple as we can,” Mueller said. Vertex should say the concept worked in an exploratory cohort and that the company was optimizing a final regimen before going into Phase III.

Smith persisted. He proposed emphasizing the super-responders in the press release. Olson sharply disagreed. “This says nothing,” he said.

“I agree,” Ken said.

“I also agree,” Wysenski said. “I don’t want to overstate the data.”

“The big whoopee is, even if we see with these patients what might be a billion-dollar curve, it still might be misleading, which could give a lot more patients a chance for a cure,” Mueller said. “I would leave it the way it is right now without any further interpretation.”

“The proof of concept is there,” Ken concluded. “The combo works. No one dropped out due to adverse events.”

Thus were resolved, in favor of not getting ahead of the truth, the tone and content of Kalmar’s press release, which claimed modestly that the data from the study “open the door to the possibility of treating people with the most common form of cystic fibrosis,” as Mueller was quoted saying. At the CF foundation, Bob Beall was similarly circumspect. “These data, while early, provide important new information about the potential to address the basis defect” among most patients, Beall commented.

VRTX skidded on the news. By midmorning, as the analysts weighed in and investors digested their mostly gloomy assessments, the share price plunged more than 13 percent. JP Morgan analyst Geoff Meacham, who as a PhD candidate had studied CF, expressed the majority view that the sweat chloride data were less robust than expected. “While the data are a step in the right direction, the synergy is very modest, and the data are by no means a ‘game changer,’ ” Meacham wrote in a note to clients. He questioned whether the cocktail would “materially alter the course of disease [or] its management.” Shares finished the day down 7 percent to $49.30, the largest one-day drop for the company in almost two years, erasing some of the 60 percent upsurge over the past six months.