The Antidote: Inside the World of New Pharma (39 page)

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 internal 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 Tuesday 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.

The regulatory operations people spent the weekend running programs around the clock to convert the NDA to its final form, squeezing it
piecemeal, section by section, through the FDA network gateway. “They have all these validation steps they have to do,” Weet explains. “They go through the table of contents. You have to hyperlink everything you say in the labeling to something in the clinical summary. Then you have to hyperlink everything you say in the clinical summary to something in the summary of the clinical studies. Then you have to link that to everything in the studies, to the tables and the appendixes. The reg ops guys had to work all those links to see if they worked. They found some broken ones.”

On Tuesday Vertex announced that it had completed the submission of its NDA for telaprevir—formerly VX-950. In its application, it sought priority review for the drug, requesting that the FDA shorten the normal approval time from ten to six months on the grounds that the medicine represented a major advance in treatment of the virus and so patients should have access without delay. “The submission is a milestone in our more than fifteen-year effort to change the way hepatitis C is treated,” Emmens declared. “We are committed to working closely with the FDA to make telaprevir available as quickly as possible to the millions of people with hepatitis C who need new medicines to increase their chances for a viral cure.”

Merck, no surprise, had gone dark, choosing not to publicize its own submission. As people left Vertex for the Christmas holidays, no one inside the company knew whether Merck had already filed, or whether its rumored September filing would yet prove to be true.

Showtime

JANUARY 9, 2011

Registered attendance was up about 20 percent from a year earlier at the Morgan conference, meaning that 1,400 more people jostled for seats at the breakout sessions. At lunchtime, thousands packed into a constricted hallway leading to the Grand Ballroom, inching ahead to get to keynote presentations by Obama’s health advisor Nancy-Ann DeParle and—as was becoming routine—Morgan’s chairman, Jamie Dimon, who’d fared best among Wall Street’s top figures in the two years since the financial collapse. “The effect is not unlike pushing to get through the gates at a professional football game, only without the face paint and the drunks,” an attendee blogged. “In this case, the elixir is money.”

Vertex was poised “to take [it] to the next level,” though not by the standard that enthused CNBC’s Huckman and nearly everyone else there: monetizing the company’s science to make an eye-popping bundle for shareholders. Sticking firmly to Boger’s vision, if not his bold presumptions and brash tropes, Emmens told a standing-room-only audience that as committed as the company was to curing liver disease, its major focus remained set on becoming the first new-model independent pharmaceutical company of the twenty-first century. He announced that Vertex planned to submit an NDA for VX-770 by the end of the year, talked up its CF combination trials, and for the first time speaking with investors mentioned the flu program. He distributed drinking straws to everyone and urged the crowd to breathe through them to get a feel for
what living with CF is like. An audience member tweeted that the straws were for sipping the company’s Kool-Aid.