The Antidote: Inside the World of New Pharma (35 page)

Boger had always equated doing well with doing good. The Pharmaceutical Research and Manufacturers of America, the drug industry lobby known as PhRMA, also considered that its mission was to ensure patient access to high-quality medicine, but its reputation was for standing first and foremost against any attempts by government payers to cut prices. During the 2003 debate over the Medicare prescription drug plan, PhRMA had it written into the legislation that Medicare couldn’t negotiate with drug companies. Now its lobbyists feared that Obama wanted to bring down drug prices and that he supported reimportation of lower-cost prescription medications.

Approaching summer recess, as the White House talked more about overhauling health care, the PhRMA operatives grew anxious. In early June, a few days after Boger cleaned out his office in Fort Washington (the company gave him as a parting gift the original door from the converted garage at 40 Allston Street where he started out), one of the lobbyists wrote to Obama’s senior health care advisor. Although Obama was overseas, meeting with Saudi King Abdullah in Riyadh, the advisor wrote back that she and other top officials had “made the decision, based on how constructive you guys have been, to oppose importation.” Two weeks later, before a packed East Room audience, Obama reversed Bush’s policy on stem cell research. He said he would release federal dollars to fund significantly broader experimental efforts because “medical
miracles do not happen simply by accident,” and he vowed to make up for ground lost under Bush and the Republicans.

“With Josh gone,” Garrison recalls, “I was out of there.” The company’s culture was set. Whether it would remain now fell to Emmens and his team, and Emmens didn’t want or need Garrison’s help. Boger’s social experiment had produced an organization that was committed to applying a different set of values to overtake markets and revolutionize institutions—including itself. It characterized what influential Harvard Business School professor of management Clayton Christensen calls disruptive innovation, though the preferred term within Vertex, since its challenges were ultimately scientific, was “disruptive technology.”

No one embodied the mission more than Murcko. “I was the guy who was supposed to think about: As smart as Vertex is, what are the things we could be doing differently, where are the opportunities that we’ve been missing, what are the out-of-left-field ideas that we should be looking at more seriously?” he says.

In 2004, Murcko had proposed that the company completely revamp the way it looked at new projects. Mueller supported the creation of a sixty-person team to look for new leads not by rational drug design or high-throughput screening but by other methodologies: a team B, so to speak, an independent global unit with Murcko in charge that would scour the environment for alternative approaches and disease areas to broaden both Vertex’s discovery system and its pipeline. Kwong, especially, was interested in pandemic flu viruses—not seasonal varieties but those killers that regularly sweep around the world, such as bird flu and SARS (severe acute respiratory syndrome).

Without knowing the protein targets, Kwong’s group started feeding molecules to infected cells to see their effects, an approach called phenotypic screening, since the goal is to observe changes in physical properties and behavioral traits and deduce from them drug targets of interest. They soon identified several tantalizing compounds. Murcko:

One of the things I was really interested in, and Peter was as well, was the idea of using cellular screening for finding new projects. The
trick with phenotypic screening is that you have to pick a screen that really does teach you something about the disease biology. We found that in the area of influenza, it was possible to construct such an assay.

The whole idea of getting the Cambridge site used to thinking about phenotypes was something that was violently opposed by many people. A whole long list of objections arose. It’s a stupid idea. We don’t know how to do it. It’s too risky. You don’t know what the target is. You can be blindsided later. The agencies won’t ever let you file for the drug if you don’t know what the target is. But we just did it anyway, with Peter’s blessing.

As with the kinase collaboration with Novartis, Murcko’s Boger-esque optimism and self-assurance failed to take fully into account the tendency within organizations, even forward-leaning ones, to resist disruption. Even as the new project group pushed ahead with flu, eventually discovering the molecular target that allowed the company to address it as a more traditional enzyme inhibition problem, the site heads complained that its centralized standards and processes were impeding the speed of discovery. Murcko countered that introducing check steps and validation steps earlier in the process would produce better data and drug candidates and that a decentralized system would be less effective overall. He lost the argument. In 2008 Mueller rolled out a reorganization that gave the sites control over which targets and diseases to pursue, effectively closing down team B and giving Murcko more time to think about where the company should be headed next.

After Boger left, Murcko pressed hardest on two main fronts where he and Mueller agreed that Vertex could stake out a lead. Cell therapy is the process of introducing living cells into tissue to repair function, a type of regenerative medicine that, from an experimental, basic biology, and drug-delivery standpoint, is the extreme opposite of designing small molecules. Murcko, seeing synergies, began to dig into dozens of cell therapy companies and develop key academic partnerships in the field. Mueller quickly became enthused by the prospects. Murcko also started building a team in systems biology, a speculative realm where complex
computations are used to understand biological processes. “A lot of the work was dodgy,” he says. But he believed the field could someday be useful and intended to stay ahead of the bandwagon.

With time to stare out the window, Murcko could do what Mueller couldn’t: look beyond Vertex’s pipeline to the medical landscape of the 2020s and 2030s. Mueller had up to twenty direct reports and a $600 million R&D budget. He received emails at a rate of one every ninety seconds, and was chronically double and triple booked. He worked sixteen-hour days, regularly bolting down to the courtyard for a cigarette. When he left, verging on exhaustion, for two weeks’ vacation in August, Emmens worried about his capacity to shoulder the ever more grueling pressures that would face him when he returned: a year of daily, critical-path deadlines leading to the submission of the NDA, with Merck and Wall Street constantly looming.

Emmens’s team building revolved around Mueller’s outsized personality and needs. Before he left for vacation, Mueller complained to Emmens about Graves, who was pushing for John McHutchison to become chief medical officer. Emmens spent two hours interviewing McHutchison, deciding quickly not to hire him because he thought McHutchison’s character and style wouldn’t fit at Vertex, and also because he was certain that McHutchison and Mueller would clash. “It would have been World War Six,” he says.

Just after Labor Day, Emmens told Graves he was making a change in commercial. The announcement, buried in a corporate update, included a perfunctory note from Emmens: “I thank Kurt for his efforts to build Vertex’s commercial infrastructure over the past two years. Today, Vertex is well-positioned to advance telaprevir to commercialization, and I wish Kurt well in his future endeavors.”

After taking over regulatory affairs, and without the buffer that Lewis-Hall had briefly provided his predecessor, Jack Weet learned quickly how far he could push in all directions and still advance toward submitting an NDA by the end of 2010. Dry witted and low-key, he had to orchestrate a complex collaboration involving R&D, commercial, clinical, US and European regulators, and J&J’s Tibotec Pharmaceuticals subsidiary,
which was located in Antwerp, Belgium—all while mobilizing a fast-morphing team of medical staff, statisticians, IT specialists, lawyers, outside consultants, and independent experts. Formerly a vice president at Bausch & Lomb, the eye products company, Weet knew the terrain, though he was unacquainted with the ways of Vertex and the players in antivirals at the FDA who would decide whether and when telaprevir would get approved.

During the summer, Graves had urged him to press the FDA on safety issues related to EPO, which Merck was adding to its treatment to help many patients overcome the anemia that resulted from combining boceprevir with peg-riba. Sold by Amgen as Epogen and Aransesp and by J&J as Procrit, the most lucrative product ever developed by the biotech industry and the largest drug expense for Medicare, the anemia drug was under harsh attack by the FDA. It had added a “black box” warning—the strongest type—to the labels of the drugs, advising doctors to use the lowest possible dose to avoid blood transfusions, and was reevaluating previously approved advertising claims that the drugs raised energy levels and improved quality of life.

“We were aware that Schering-Plough was using EPO in their trials with boceprevir. We knew they had an anemia problem,” Weet recalls. “We also knew there were safety issues related to EPO and that there had been safety warnings sent out by FDA relative to the use of EPO. So Kurt put a lot of pressure on me, saying, ‘Write a letter to the FDA. Tell them they shouldn’t be allowing these studies to continue because they’re using a product that isn’t approved for use in hepatitis.’ ”

Weet thought it was a good point. He composed the letter, signed by several Vertex executives. “We got this pretty nasty letter back saying, ‘Mind your own business. This is under our auspices. Butt out,’ ” he recalls. Though the tone was stark and negative, Weet considered the response useful in making it clear inside the company that if Vertex wanted to succeed, it could no longer act in ways that smacked of its earlier arrogance or made it appear that its controlling motive was profits, even if that wasn’t how it saw itself. It showed everyone where the boundaries were.

Not all contact with the FDA was toxic. Kwong, Tara Kieffer, and
Dr. Shelley George, who had taken over the clinical trials from Kauffman, worked closely with the FDA and outside researchers on the unfortunately named HCV DrAG, a working group that focused largely on resistance issues. Kieffer and George had had positive dealings with Russ Fleischer and his team. Approaching the upcoming Liver Meeting, Weet expected that Vertex would face the usual controversies. He saw an opportunity to calm the waters by arranging to bump into Fleischer. He recalls:

My goal for that meeting was to track him down, not to stalk him. In previous AASLD meetings, he just went after the people who manned our booth like a pit bull. He was tearing them to pieces, criticizing them, just raking them over the coals, saying they were doing preapproval promotion and all this kind of stuff. And internally, people were asking me, “Please, hang around the booth, because if Russ comes, we’d like to have you sort of stand between us”—like another guard dog, for interference. I said, “I’m happy to do it.”

Weet approached Fleischer delicately, but directly, as if he’d happened to wander over.

I said, “Russ, I’m Jack, I’m the new guy here.” He said, “Oh yeah, I’ve seen some letters that were signed by you. You’re one of the ones that signed that letter about EPO, weren’t you?” I said, “Look, I’ve been doing regulator stuff for twenty-five years. Never had a bad relationship with FDA. Don’t expect to start now. My philosophy is I work with FDA, I take your counsel, I take your advice. I’m not here to tell you anything or cajole you in any way. If you have a problem with our booth, you call me. Here’s my card. Don’t hassle these guys. They’re just doing their job.” We had a nice conversation. A wall just came tumbling down.