The Antidote: Inside the World of New Pharma

by Barry Werth

  On his first morning in Cambridge, Cumbo screened the accumulated résumés of those seeking jobs as Vertex sales reps. There were about four hundred of them. He found them all useless and sent them back to HR. What he was looking for were not just the best, most experienced managers, trainers, and reps in gastroenterology and infectious liver diseases, but people like him who were doing very well and were happy in their present situations but would find the allure of being part of the next big thing in the field ultimately overpowering.

  To identify these people, Cumbo contacted the KOLs, who more than anyone else knew and could recommend the reps from the eight companies that dominated in antivirals. Getting top prospects to leave their jobs was something else. “Specialty reps are out on their own islands,” he notes—isolated from their colleagues and the home office. Their connections to their companies channel wholly through the products they promote and the reporting chain. With the disadvantage of representing a company that still, after twenty-one years, had no products or profits and had burned more than $1.5 billion in the past three years alone, Cumbo found it “very, very challenging.”

  He says, “I felt like I was that college football coach recruiting players: ‘Why don’t you come to our school? I know we’re not LSU or Auburn, but we’re Southern Miss, and you can come over here, and we’ll take care of you.’ I had to actually talk to a couple of my representatives’ wives to make them feel at ease, because they were scared. They have families, they have kids, and they don’t want to come over here and the drug not get approved and fail.”

  A sales leader leads by selling the value of personal experience. Cumbo told them his own story, a pilgrimage that in its contours and parallels sharply resembled Boger’s and many others’ at the company, but with the notable distinction that he had his epiphany not long after he launched Agenerase. He was at Glaxo, and the company was selling $7 million a day in HIV meds—70 percent to 80 percent of the AIDS market at the time. Bristol-Myers was its biggest competitor, with Sustiva, the first once-a day-medicine for HIV.

  Cumbo lunged, joining Gilead. The small company had seen its market share collapse after its first drug failed, but it now had a promising once-a-day treatment for HIV called tenofovir, a non-nuc polymerase inhibitor. “My marketing manager called me up and said, ‘Why are you going over there? They’re gonna get bought out. Or they’re only gonna get ten percent market share. Most likely you’ll end up on the streets if it doesn’t come to market. It has renal issues, bone issues. You’re making a huge mistake. We’re Glaxo.’ And I’m like, ‘You know, I can just see where the market is gonna go. I can tell you that it’s gonna go once-a-day.’ The arrogance at GSK was very thick at the time. They were the dominant player; thought they were invincible.”

  Cumbo’s parable dovetailed neatly with Boger’s story line about Vertex being the next challenger to the twin legacies of Genentech and Gilead. The fact that Gilead had displaced Glaxo in the marketplace, that it now was the behemoth in AIDS and scrambling to expand in antiviral therapies with an unproven play in HCV, added further resonance. The interviewees would hear, as part of the company’s pitch, about the three Vertex values, but what they connected to and drew strength from was Cumbo’s warmth, inspiration, reverence for history, and go-big-or-go-home commitment.

  I’d say, “Look where Gilead is. You just don’t know what’s gonna happen, but you have to take a chance. The people who take a chance have a lot more to gain. Do you want to stay at that company that’s doing eight billion and just be that average rep, or do you want to be the guy who comes over here, tries to create things, build things, and take down the biggest players? I mean, that’s fun.”

  I’d say, “Previous success isn’t future success, but at least you’re part of the game.” And being a part of the game is what drives you. It gets the blood going. That’s why I can tell you that the people who join are all sort of cut from the same cloth. These are the people who want to run through a wall and change the entire pharma industry, by beating Merck.

  In August Merck announced that it had completed its second pivotal Phase III study, tightening the race and ratcheting up the pressure inside Vertex. A new compressed timetable came into play. NDAs are filed confidentially. Once the FDA received either company’s NDA, it would have six months to make a decision. If the agency decided it was warranted, it could convene a public hearing with a panel of outside experts, an advisory committee, or AdComm, which by a vote would recommend action. Whichever company submitted its NDA first would determine the AdComm date, but since AdComms convene only one or twice a year, it was possible, if Merck or Vertex submitted its application soon enough, it could set the other company back by six months—an eternity in a head-to-head marketing war.

  Rumors reached Vertex that Merck had filed its NDA. In Vertex’s NDA war room, a secure conference room on the first floor of Fort Washington II across from Weet’s department, anxieties spiked. Weet had contracted with a consulting company, ProEd Regulatory, to come in and facilitate its preparations for the advisory committee. The company had decided to treat the pre-NDA meeting as a dress rehearsal for the AdComm, yet the first preparation session had been a shock. ProEd’s team drilled Vertex’s people, and feelings were raw. “I remember Ann Kwong sent me a note: ‘I’m glad Peter wasn’t here. If he was, there would have been blood on the floor,’ ” Weet recalls. “It was awful. ProEd was throwing us questions as if they were FDA. We weren’t able to answer them. We were fumbling over the responses. We didn’t know who was gonna answer them. It was really chaotic.”

  It was Kauffman, who had been with the project for a decade, persisting on behalf of VX-950 after Eli Lilly dropped out, who emerged from the session as the team’s leading voice. Kauffman dismissed the rumors that Merck had submitted its NDA. He knew the general timeline for its studies and believed “there was no way in the world they could file that early.” Still, with everyone at Vertex working to exhaustion to meet a target filing date of late November, the rumors tested his equanimity. “We had a timeline, and as much as Peter was trying to push us, we just could not accelerate any further,” he recalls. “A certain number of things needed to be done. In the end, we just couldn’t read the documents fast enough. If you want to actually review them, there’s a limit to how much you can read. That was a time of real anxiety, and I was a little pissed off by that point. Ten days’ difference didn’t bother me much, but for them to be ahead of us by that much after we had been ahead of them for all these years would have made me really mad.”

  Kauffman had been in the role of NDA lead before, at Syntex with the immunosuppressant CellCept. Weet, too, had experience in getting organizations in shape for the FDA review process. At his last company, NDA teams decamped to another city so that senior executives wouldn’t panic or intrude and exert pressure to influence the drug’s label. At Vertex, the preparations were shadowed by Tibotec, which would be applying for European approvals. Weet took the information that Merck might be ahead gravely. “We didn’t know when or if they’d submitted,” he recalls. “There was some intelligence that leaked out that they had actually done their submission in September. We thought. ‘Crap, what happens if they submitted in September, and they have a February advisory committee? We’ve got to get our NDA in as soon as possible.’ What was driving us was this idea that there might be this advisory committee sitting out there in February and we missed it, because we didn’t get our submission in.”

  ProEd organized two mock sessions for the pre-NDA meetings, bringing in a former FDA official in charge of viral products and two senior KOLs, and setting up in a conference room at the Cambridge Hyatt Regency, a short walk from Vertex. They fired away at Kauffman, who either answered or deferred to the person in the group who knew the data better than he did. For Weet, the critical goal was to get the FDA to agree that Vertex had sufficient content to back up its claims, so there would be no refusal to file.

  The Vertex group, exhausted and strained by inte
rnal politics that produced sore feelings but no smashed furniture or defections, flew together to Washington for the pre-NDA meeting in Silver Spring. Cumbo and his recruitment team had been on the road for six weeks. Vertex had established hub cities for conducting mass round-robin interviews. Candidates cycled through three interviews in succession, and if they looked good, they met with Cumbo, who averaged twelve interviews a day. After a burst of hiring away more than two dozen sales trainers and reps from Gilead, he got a menacing letter from the company’s lawyer, then its head of commercial, warning him to quit poaching. Emmens received similar threats.

  At the meeting in Silver Spring, Weet, Kauffman, Wysenski, Mueller, and the rest of the Vertex group encountered effectively for the first time their opposite contingent: the senior people in antivirals and numerous other agency sections who would govern the reviews of both telaprevir and boceprevir. Weet expected that the old contentiousness was well known, and that the improved relations between him and Fleischer would make the division heads and department chiefs curious about the company. Merck, despite the Vioxx recall, remained something close to the gold standard for smart regulatory dealings. The question of whether the old Merck or the former Schering team was now driving boceprevir was debated exhaustively at Vertex.

  Twenty-five FDA officials crowded into a conference room to hear Kauffman deliver Vertex’s data package for telaprevir and the rest of the evidence supporting the company’s claims for its superiority over peg-riba alone, across all patient groups. The officials asked to see a few slides, but otherwise the discussion was more of a scientific dialogue than the skeptical, Supreme Court–style grilling that most of them had prepared for and expected. The regulators agreed to sufficient content for filing. Kwong, Kauffman, Weet, Wysenski, and the rest of the group were impressed by the depth and acuity of the questions, the delicate position faced by the officials in having to evaluate two competing products at the same time, and their strong willingness to work together with the company.

  Regardless of the jockeying with Merck, the meeting was a critical test of Vertex’s readiness. All signs were encouraging. “It had very much the look and feel of an advisory committee,” Weet says. “It was showtime. Peter was literally dancing in the halls after the meeting. He was doing his happy dance in the lobby of the FDA.”

  The National Conference on Correctional Health Care in Las Vegas in late October focused on the problem of AIDS and hepatitis C in the country’s prisons and jails. More than 40 percent of inmates in California were reportedly infected with HCV. Men and women over fifty behind bars represented a major market for new drugs, but so far prison health officials had seen very little reason to invest scarce medical resources to help them. High HIV coinfection rates were swamping prison hospitals with a complex secondary epidemic. Cumbo, from his work at Gilead and his contacts in the field, was Vertex’s obvious point person with the wardens, prison doctors, public health experts, government officials, and patient advocates assembled for three days on the Strip. He flew to Nevada for the weekend conference while his staff moved on to next week’s hub.

  Cumbo had been feeling exhausted, run down. “I woke up in the middle of the night and couldn’t breathe,” he recalls. “I called a doctor I used to work with at Gilead. He was at the conference. I told him my symptoms and he said, ‘You need to go to the hospital.’ So I went downstairs with a colleague, Alex Alvarez, to get in the taxi. Alex turns to the taxi driver and says, ‘We need to go to the hospital.’ And the driver says, ‘Which one?’ And Alex says, ‘Take us to the one where there’s less gunshot wounds.’

  “So we went to the place. It ended up I had walking pneumonia. They gave me IV antibiotics and fluids. I checked myself out of the hospital at ten in the morning because I had a twelve o’clock appointment. I went back to the conference and kept my appointment.”

  If the Vertex sales reps wanted to run through a wall for their leader, they had their man. The battle with Merck was in high gear, and every confrontation was heightened inside the company by the sense that it was not just a head-to-head drug launch in a hot disease area but a title match, a fateful duel. Boger could not have scripted the showdown more perfectly if he’d tried—with one large, annoying exception: boceprevir wasn’t a product of Merck’s R&D but of Schering’s, and it wasn’t yet clear which Merck contingent would show up at the AdComm and in the field when the drugs were approved. In a more perfect world, Merck’s molecule would have emerged from its own labs and been promoted by Merck’s vaunted field force, but Boger couldn’t expect to have everything.

  The Liver Meeting in Boston was packed to overflowing, with more doctors and investors and analysts and company reps in attendance than ever before. Veteran doctors and public health officials felt the sessions had the same sudden aura of abrupt optimism and excitement that gripped the AIDS world in Vancouver in 1996, the year HIV protease inhibitors became the backbone of combination therapy—although now with more of a car-show feel, as Vertex, Merck, Roche, Gilead, and numerous other companies staged sleek sales and/or information booths in the caffeine-juiced lower-level exhibition hall. The sense of promise also raised the same problems and questions: What now?

  Doctors were concerned that the new treatments wouldn’t be an easy regimen, no matter which drug they chose. Compliance, already an issue, could become worse, especially with the introduction of a fourth toxic drug, EPO. Companies, investors, and analysts looked at the competition and the progress toward an all-oral treatment and tried to read the future a decade out. Where will the market go next? What’s the shelf life of any one product? What would the new drugs cost? Who would have access to them? What about the hundreds of millions of HCV-infected people around the world?

  Standing-room-only crowds packed the rooms where Vertex and Merck announced new data. The vital issue was how to compare two products that hadn’t been tested against each other in clinical trials—indeed, whose trial designs differed widely and, in some cases, deceptively. Doctors who wanted to know which drug to give their patients could be forgiven for being confused and annoyed by the lack of apples-to-apples controls, but neither company desired a head-to-head trial for the obvious reason: it might lose.

  Most Wall Street analysts agreed that Vertex had the better medicine—more potent, faster acting, safer, easier to use. The race to submit its application first, or at least keep the submissions close enough to avoid missing an AdComm, beat on inside both companies. The rumors of Merck’s alleged September NDA filing still jangled already overfiring nerves at Vertex, where everyone in Cambridge, even Emmens, was susceptible to the terrible scenario that even one missed deadline could, after nearly two decades of pathbreaking work, irreparably set back the scheduled launch of telaprevir, derailing the company.

  Since the pre-NDA meeting, nearly everyone in clinical, regulatory, and regulatory operations—the team that would finally put Vertex’s one million pages of documents into a proper format for electronic submission—had become riveted on the November 28 deadline. A fast time from the moment the last patient in the last trial visits the clinic for the last time until an application is ready and thoroughly vetted is six months: Vertex had given itself four. The team followed a game chart linking time and events, with top priority going to polishing the data from the big European study, 216, alongside a group from Tibotec, which planned to submit its application two weeks later and was ensconced in another building on Hamilton Street, across from the gritty do-it-yourself auto repair shop owned and run by National Public Radio’s Car Talk guys, Tom and Ray Magliozzi. By the Liver Meeting, several groups began hammering out a label that followed a common technical document format, submissible on both sides of the Atlantic. Where interpretations varied, or when European and American regulators had different policies or standards, tense standoffs on wording went on for days—and, on one occasion, weeks—sorely fraying nerves and stretching timelines taut.

  Internally, Vertex set an accelerated date of November 23—the Tues
day before Thanksgiving. By the end of the previous week, the documentation was finalized. It was studded with a million hyperlinks so that the reviewers could cross-check, within the allotted sixty days before filing, every statement of fact and data point. Mueller, Kauffman, and Weet each reviewed the application in considerable detail. “We got it all done and wrapped up, and Bob stood up and said, ‘I just have to say that this is probably the most special moment in my entire career,’ ” Weet recalls. “You could tell it was very emotional for him personally. It was kind of emotional for the rest of us too. Number one, because it all of a sudden relieved the pressure. But also, because we could say, ‘We really have a drug here.’ ”

  Champagne flowed in the war room, although after seventeen years, those celebrating—except for Kauffman, Mueller, and a few others—were not the same people who had made telaprevir. The baton had started with Deb Peattie and Charlie Rice, and then soon passed to Thomson, Murcko, Tung, Sato, and the other early champions of the program. It dropped to the ground with the collapse of the Lilly deal, and then was scooped up by Alam, Kwong, Kieffer, Hurter, Condon, and untold others before ending up now with Kauffman, Mueller, Weet, and their people. The inspiration for the drug had passed from individuals and groups before any of them could have more than a passing claim on true authorship. A drug, unlike a social network or a mobile app, was not something that you could dream up in your dorm room and turn into a billion-dollar seller or a $100 billion company. It was an ultramarathon relay in 100-degree heat. Boger, who had enabled it all to occur, was, of course, elsewhere.