The Antidote: Inside the World of New Pharma (38 page)

Robert: PUT ME ON TRIAL TO SEE IF IT REALY [SIC] WORKS

Accelerating Vertex’s internal pulse were several converging deadlines. While Kauffman and his clinical team pushed to finish the two pivotal studies, Condon circled the world assembling the last crucial pieces of his virtual supply chain, and Weet and his group started compiling, hyperlinking, and submitting the mountain of data the FDA would require for filing an NDA. In every important meeting and discussion—holding what Boger, Emmens, Smith, Murcko, Ken, and many others worried were too many reins—was Mueller, dressed in his creaseless black uniform, often with a pale-hued pressed sweater draped crisply over his shoulders, peering over half-rim glasses in Bavarian field-general mode. Meantime, with Emmens promising Wall Street that the company would submit its application by the end of the year, Wysenski scrambled with headhunters to fill the yawning gaps and vacancies in the commercial organization, and Cozzolino laid the groundwork for putting a sales force into the field.

“It was very, very intense from beginning to end,” Kauffman says, “because we were pushing timelines that most companies would not have tried to do. And the data were continuing to flow. There was an enormous amount of effort going on. Part of the pressure was self-induced. We at Vertex really wanted to prove ourselves. We wanted to do a good job and show that we had really made it. The other thing is, every day of delay is a day of sales, and you just want to get this thing done as quick as you possibly can.”

At the end of May the first data on the ADVANCE study—clinical trial 108—were unblinded. With over a thousand patients, it was the biggest study ever done on people infected with HCV. About 75 percent of patients receiving the standard dose of telaprevir for twelve weeks in combination with peg-riba still had no detectable virus in their blood twenty-four weeks after treatment—essentially a cure—compared with 44 percent of those who received standard therapy alone. Vertex’s stock jumped 12 percent in after-hours trading. Yaron Werber, an analyst for Citigroup, estimated that global sales of the drug could reach $3 billion a year within five years.

ADVANCE and another Phase III study, REALIZE, gave Vertex most
of what it needed to submit the drug for approval, but a third large pivotal study called ILLUMINATE—trial 216—was still under way in Europe. Because of the difficulties Alam had encountered with the agency over submitting the company’s Phase III protocols, there remained some ambiguity about whether the studies would be adequate. Jack Weet was anxious. Vertex had requested a target date of September 28 for a pre-NDA meeting. At that point, it would outline the content and format of the NDA. If there were problems with either study, the result could be ruinous. “The way regulatory works is: you submit an NDA, the FDA files it,” Weet says. “They have sixty days. Within that sixty-day period, they can come back and say, ‘You don’t have enough data, or the data that you have aren’t sufficient,’ and they can refuse to file. If they refuse to file it, that can kill a company. That’s what happened to Imclone. They refused to file the company’s application. Our stock would go down to zero if we had an RTF (refusal to file).”

Now in regular and cooperative contact with Fleischer and dozens of others at the FDA, Weet and his team pressed to accelerate the process. Waiting to hear about the pre-NDA meeting, he asked if Vertex could submit the ADVANCE data ahead of ILLUMINATE, so that if there were questions, the company would have time to address them. Was the study robust enough? Were there enough patients? Were there enough African-Americans? Weet hoped a rolling submission on the two trials would relieve some of the pressure he was feeling from Mueller and keep Vertex a step ahead of Merck, which was finishing two pivotal studies of boceprevir and also had announced that it expected to submit an NDA by the end of the year. As deadlines tightened, so did nerves.

“It got to the point,” Weet recalls, “where we decided we’re all going over to Antwerp because we’ve got to get the briefing document done, and we can’t even spare six hours’ time difference for them to get data and send it to us. The team flew over. We literally sat down with Tibotec as they unlocked the database and unrolled what the data said. We didn’t know until that week what it said, so we had our writers there, we had the clinicians there, everyone together hammering out the document and the key response data. We packaged it all up in a pre-NDA submission,
sent it out at the end of the day there, so that it got here in time to get it into the gateway that same day. We literally didn’t have six hours to spare. We were hanging on by our fingernails.”

Joe Cozzolino hired Alexander “Bo” Cumbo away from Gilead to build Vertex’s US sales force for telaprevir. As fellow rising stars there, they both “knew what good looked like,” as Wysenski liked to say. More to the point, Cumbo knew the KOLs, not just nationally but region by region, city by city.

Reared and educated in Alabama, he was soft spoken, mannerly, silver haired at age thirty-nine, compact, and driven, an evangelist for antiviral drugs. If he hadn’t gone into pharmaceuticals, he might easily have excelled at coaching or religion. A couple of years after graduating from Auburn University in the early 1990s, Cumbo, single and unemployed, took a job in Jacksonville, Florida, selling vitamins and birth control pills. After interviewing at Merck, Roche, and Glaxo in 1997, he chose Glaxo because it had the biggest HIV program, and because he wanted the pace of change and the opportunity that a fast-moving disease area could offer. He covered a territory stretching from Jacksonville to Savannah and Macon, Georgia, to Mobile, Alabama, and back, and for the first time but not the last he worked himself into the hospital, needing IV fluids. Cumbo joined Gilead in 2000, when it was on the verge of launching its first AIDS drug, and he had held senior positions managing state and federal accounts and sales to prisons. Telaprevir would be his tenth drug launch.

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.”