by Barry Werth
Emmens, like Boger a year earlier, did a hallway interview with CNBC’s Mike Huckman. When anchor Larry Kudlow cued the segment by saying that the Morgan meeting’s seven thousand attendees were a who’s who of those making news in biotech and those who knew how to make money from it, Huckman said, “Good Morning, Larry, yeah, this year in that group of see and be seen is Mr. Sam Waksal, of course the Imclone founder and ex-con.” It was a theatrical reminder of the scandal that also put style-maker Martha Stewart behind bars, after Waksal, a friend, told her that the FDA was about to turn down an Imclone drug for submission, and she sold her stock before it sank. Huckman turned to Emmens:
HUCKMAN: You’re going to have, as I mentioned, major data rolling out this year on this drug that you have in late-stage development for hepatitis C. You plan to file for FDA approval of it by the second half of this year. But Merck is close on your heels in development with a similar drug. Is it gonna come down to whose data is better, whose drug works faster, whose drug is safer?
EMMENS: Well, I can’t predict the future. But I can tell you that our data look real good. The drug has been pretty consistent in clinical trials. We plan to launch that drug sometime in the first half of next year. And it works really well for those patients who have failed the current therapy.
HUCKMAN: Mr. Emmens, as you well know, this is a place—this event—where deals historically have been born. Are you being approached by Big Pharma, by Big Biotech? Or does your partnership with Johnson & Johnson put handcuffs, if you will, on other suitors?
EMMENS: Mike, we get that question all the time. That’s gonna be up to our shareholders. But I’ll tell you one thing. We’re here to build as much value as we can, first with the drug for hepatitis C, then with cystic fibrosis. We have twelve more preclinical projects. We have now six programs in the clinic. So the scale of our company is quite amazing.
HUCKMAN: Yeah, but certainly an acquisition would create shareholder value?
EMMENS: We’ll have to see.
Boger thought the reason business reporters and analysts persisted in fanning the takeover-target story line was that they still didn’t understand Vertex’s business model and the risk-mitigation strategy embedded in its portfolio. Emmens thought it was because he and Wall Street were in totally different businesses. His was to make new medicines. Theirs was to make money speculating on changes in the price of VRTX due to short-term developments and chatter. Back in Cambridge, he faced challenges but no one had the sense that he was any less committed than Boger to keeping Vertex from being taken out.
Scott Brown’s startling Senate victory burst through the halls of Congress and across America. The political center of gravity lurched rightward. “Tonight the independent voice of Massachusetts has spoken,” Brown told his cheering supporters. Kennedy had called overhauling the health care system “the cause of my life.” Now the state would send a Republican to Washington to try to kill it. Losing their supermajority, Democrats scrambled to salvage Obama’s bill. PhRMA and BIO both backed the measure, the big drug companies having made a deal with the White House to block any effort in Congress to extract cost savings from them beyond an agreed-upon $80 billion, and BIO having inserted a provision to create an accelerated pathway for the FDA to license so-called biosimilars that were interchangeable with branded biologics.
Wysenski had twelve months to build a national commercial organization equipped to go head-to-head against Merck. Absorbing Schering’s clinical and marketing muscle in hepatitis C gave Merck an initial advantage in the market, where the Schering team already knew and had contracts with nearly all the key opinion leaders (KOLs) in liver diseases and gastroenterology, and had friendly relations and well-established channels across the reimbursement landscape. Conceptually, designing an organization requires figuring out what your goals and priorities are, and then reverse-engineering from that what it will take to be successful. With the sharply reduced market expansion forecast, Wysenski now had reasonable goals for the launch and beyond. With a small team, she started to devise a framework.
“There are three buckets,” she explains. “A strategy drives people, process, and technology. That’s what I assessed, and that’s exactly what I took to the board. I said, ‘I’ve looked at the people, and we’ve got great middle-level management, but I’ve got to hire around that. It’s not that they’re not good, it’s just that they’ve never done the lead roles, so I’ve got to supplement that because we can’t fail.’ You couldn’t worry about people being a little bruised, because you had to make this happen for the company.”
Wysenski fleshed out her proposal to the board. There were five core technology systems that Vertex would need to be ready to go on Day One. She identified the five key positions and the talent she would need. She also spelled out the processes by which everything would come together—“the operations, the policies, the infrastructure, the organizational structure you create”—and, with the help of one of Murcko’s hires, created a program management system to track what was getting done. As spring approached, with Emmens’s blessing and the board’s support, Wysenski dove into delivering on her plan to turn Vertex into an operating company.
“I immediately started aggressively recruiting on what I thought were the most important three critical jobs: sales, managed markets, head of marketing for HCV,” she says. “I also met with the CF team and told them, ‘Please don’t take it personally, but it looks like from a distance you’re doing a great job. Just keep doing it; I’ll be back in about six months.’ They were on autopilot. They had the core there.”
As Emmens had anticipated, many people in the company were jolted by the abrupt change in style brought on by Wysenski’s commercial thinking. Wysenski knew what she needed, and it wasn’t advice from people who had little or no experience in her world. She created her own subculture, a specialized army within an army. She knew she was treading on the company’s mores but thought the need to do what needed doing trumped social norms, especially given the culture of open, democratic argument that drove Vertex from its earliest days. Wysenski:
In an operating company, that debating can leave people with a sense of chaos on occasion. Because you never really know, “What did we decide?” I just had to shut that down in commercial and say we’re not going to have that. Let’s be clear about what our job is, each of us, and how we can help the person next to us. We have to start specializing because that’s the only way we’re gonna be effective. There were some people who didn’t like it because it meant their job wouldn’t be as fun. But it worked, and we got it done.
Along with that debate, I think there was a sense that commercial is so simple, we could just read about it. There I had to push back too. There wasn’t much respect for the wisdom of experience on the commercial side. And maybe a sense that it was easy—easier. And therefore, if we just thought hard enough about it, we could probably figure it out. But that’s not the case. You really do have to have people, and that’s what I was looking for. People who had the experience. People who had been through it before. People who had fallen and skinned their knees and learned from that, who could come in and drive the commercial buildout and execution.
She would have preferred to hire a managed-markets person first, since in pharmaceuticals you can’t sell your product to your customers, and your consumers can’t get it, until your payers are willing to pay for it. You have to have access to managed care reimbursements before your reps can really sell. Instead, she hired her sales lead first. Joe Cozzolino had a proven track record: he was Gilead’s senior director of sales for the East HIV Division that generated yearly sales of $3.5 billion. “Joe, technically, had everything it took,” Wysenski says. “He was a great guy. Great, great sales leader.”
Obama won his landmark health care overhaul—the most expansive social legislation in forty years—at the end of March. He signed the measure, the Patient Protection and Affordable Care Act, during a raucous ceremony in the East Room. “The bill I’m si
gning will set in motion reforms that generations of Americans have fought for and marched for and hungered to see,” he said. “Today we are affirming that essential truth, a truth that every generation is called to rediscover for itself, that we are not a nation that scales back its aspirations.” Republicans attacked the measure as an example of big government run amok. “This is a somber day for the American people,” House Republican leader John Boehner said. “By signing this bill, President Obama is abandoning our founding principle that government governs best when it governs closest to the people.”
As with AIDS, the first approved HCV protease inhibitors would surely usher in a new era in treatment. But the larger prize remained a superior cocktail: ideally, one that would further shorten the duration of therapy while sparing patients peg-riba’s grueling side effects. Since taking out ViroChem in order to acquire the non-nuc 222, Vertex had pressed to stay ahead of a phalanx of competitors advancing a variety of approaches. Bristol-Myers Squibb developed a protease inhibitor to be used in combination with a compound that blocked a fourth target, NS5A, a nonstructural protein with its finger in multiple pathways and a key modulator of viral reproduction. Roche and its collaborators Pharmasset and InterMune were attempting to combine a protease inhibitor and a nuc. So was Gilead.
In March Vertex announced it had begun enrolling one hundred patients, chiefly in the United States, to test its combination treatment. The telaprevir dose stayed the same for everyone. Some patients got VX-222 taken, at different doses, as a twice-a-day oral pill. Others received both medicines in addition to peg-riba. “No one has proven the point that you can get an SVR without pegylated interferon and ribavirin,” Kauffman told Xconomy’s Timmerman. “It’s a leap that has to be made, and we want to be the first to make it.” Whether two antivirals would be strong enough to kill all the resistant variants, or whether a third, or a fourth, would also be needed was a crucial scientific and commercial question, as Vertex, like every other company, gamed out the future of the disease.
After ten years with no new advances in treatment, patients who knew they were infected with HCV were growing desperate and, due largely to an explosion in online information and interest, more and more sophisticated about the process of bringing a drug to market. They were no longer voiceless in society. Social media gave hepatitis C patients a new forum, and everywhere the cry was for a cocktail that would save them and their loved ones from having to endure the standard of care. Kauffman’s vision of an interferon-free treatment elicited a small avalanche of hope-filled readers’ comments to Timmerman’s post:
Michele: My husband did the pegintron/ribavirin shuffle three times. The first two times the side effects were miserable but his viral load dropped to undetectable for several months until it gradually returned. The third and last time he developed interferon psychosis, which leaves him with no current treatment option. A new combo therapy without interferon would be a life-saving dream.
Diane: I hope and pray that a new drug therapy minus interferon will be developed. Was on the combo therapy and although everyone on treatment gets hemolytic anemia, I developed autoimmune hemolytic anemia, meaning my own white cells were targeting my red cells, caused by interferon. If anyone knows about non-interferon based trials, please post. I’ve got a lot of living to do . . .
William: all I hear is about relapsing 6 to 18 months after treatment. are there any people out there that are still clear of the virus 5-plus years on? i never hear of any and am beginning to think it never goes away. great for the drug companies. am coming up on 24 weeks of standard treatment plus first 12 weeks were also with experimental drug. standard flu symptoms all the time, horrible eczema, and am feeling a little nuts and miserable to everyone. is it really worth it?
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 re
sponse 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.
