The Antidote: Inside the World of New Pharma (62 page)

In late June, Vertex released more comprehensive data from the CF combination study that, although similar to the revised findings, weren’t quite as robust. Some investors again became upset. “I don’t think we lost anybody along the way but all the investors hated the volatility,” Partridge says.

The SEC, apparently finding nothing of interest, ignored Grassley’s letter.

Keith Johnson listened to the CF conference call. He believed on the basis of the company’s explanation that his FEV1 numbers during the 770 trial qualified as “statistically significant and clinically meaningful”—Wright’s, and the FDA’s, classic definition of relative effectiveness. He couldn’t understand why he was being blocked from getting Kalydeco when he had already shown that the drug had changed his life.

He imagined becoming a kind of experimental tool, a guinea pig, not just to aid Vertex’s and the CF community’s understanding of the drug, but also to dramatize an evolving model of personalized medicine, which the FDA was now trying to help accelerate by streamlining the process of clinical testing to allow, effectively, cohorts of one. He considered offering himself to the company, his doctors, and the foundation as a critical addition to their database—a patient with a CFTR folding mutation who nonetheless could be helped by a drug designed to improve gating activity. Johnson realized that by now he was consumed, but in his mental dialogue with the medical community, he believed his militancy was totally reasonable.

He honed his pitch: “This is what’s in it for you. If I’m wrong you won’t hear a peep from me again. If I did two percent, I did two percent. I’ll move on with life. I can’t go to sleep at night because I’m convinced that I’m way better than two percent. I need to take Valium-strength meds to go to sleep because it’s maddening to me. So somebody has to show me: either I’m only two percent—then I’ll leave you alone—or these numbers are meaningful and significant, and let’s agree that they are. I need to know.”

Van Goor had long ago anticipated that when personalized medicines became available, diseases would become more personal too. Since your genes would qualify you as a promising patient, more and more you would need to build a case that a treatment might work for you, then convince the medical world to let you have it, even if a year’s supply cost more than your house. No one knew how this new system would work. Advocating for himself, trying to keep up his health until 809
or 661 reached approval, Johnson was becoming an inadvertent, crusading forerunner on a new medical frontier: the informed genotypic consumer.

On June 27 the Supreme Court upheld Obamacare, removing the issue of its constitutionality from the wider political debate, and giving Obama an unanticipated boost toward reelection. A few days later Glaxo agreed to plead guilty to criminal charges and pay $3 billion in fines for promoting its bestselling antidepressants for unapproved uses and failing to report safety data about a top diabetes drug. The largest settlement ever involving a pharmaceutical company, the agreement came on the heels of a $1.6 billion settlement against Abbott over its marketing of its antipsychotic drug Depakote to nursing homes and as much as $2 billion in fines against J&J for the same offense.

During the next quarterly call in late July, Vertex and VRTX reached an uncommon equilibrium, one of the rare junctures in Vertex’s recent history when Wall Street’s on-again, off-again faith in its talents and its future trumped pessimism and uncertainty. Though Incivek sales dropped, auguring a lower, truncated revenue curve as doctors and patients awaited the arrival of all-oral regimens, shares surged 5 percent based on promising viral kinetic data from a small human study of Alios’s lead nuc, ALS 2200. The molecule was as potent, and apparently as clean, as Gilead’s lead compound, yet unlike Gilead and BMS the company hadn’t spent billions of dollars to acquire it. “It puts them back in the hep C race,” Garret and Co. analyst Brian Skorney told the daily industry news service FierceBiotech. “It makes them a real player again.”

Not that this was news inside the company. Vertex had never stopped advancing. If the drubbing of VRTX during the previous year’s hep C mania had a major internal effect, it was to incite the ET to step up its offense while forcing its members to impose stricter austerity on their organizations. Lowering the company’s sales forecasts while acknowledging that Gilead was the new front runner meant everyone would have to do with less money than they thought they would have, while accepting the likelihood that things might get worse for a couple of years before they got better. For the sales force, it meant selling harder to fewer
doctors, trying to reach those patients who couldn’t wait two years for the next generation of drugs. Near-term expectations dimmed even as the long-term outlook improved. The launch had been a blur. People throughout the company were tired but acted resolved, as usual, not to hold anything back.

“If you go away for a couple of hours,” an industry wag noted, “things change in HCV.” Now that a herd of companies was racing hard to deliver the next wave of treatments against the virus and dominate a possible $20 billion market, this advice became literally true. The shape of the race shifted again in just the next few days. BMS announced it was shutting down the combo trial with Inhibitex’s nuc after a patient who took the drug died of heart failure. By the time the company killed the development program three weeks later a total of nine patients had been hospitalized, raising long-standing safety concerns about nucs and leaving executives to explain the crash and burn in less than eight months of a ballyhooed $2.5 billion investment. The FDA, concerned about similar modes of action, called for a hold on development of the two nucs from Idenix that Adam Koppel believed would have solved all Vertex’s problems.

Vertex, playing catch-up, suddenly caught up, not to Gilead or Abbott in the next phase of what FierceBiotech called “the hep C pill race”—coming to market with the first interferon-free regimen—but the phase after that, when people with encroaching liver disease would likely choose among several treatment options based on a combination of viral genotype and their own genetic profile. Even if, as Wall Street assumed, Gilead introduced an all-oral cocktail in 2014, how many patients could the company treat? Seventy-thousand a year would be a stellar number. Yet in the United States alone, more than 3.2 million people were infected, 75 percent of whom didn’t know it. With hepatitis C, as always, the larger prize was the demographic bulge of millions of people who weren’t sick now but whose livers would become scarred and cancerous as they aged.

In late August, six years after Boger and Sachdev sat down to figure out how to leverage Washington to address the public-health dimensions
of hepatitis C, the Centers for Disease Control urged all baby boomers to get a onetime blood test for HCV. CDC officials said they decided to issue the recommendation after they calculated that the number of Americans dying of hepatitis C–related disease had nearly doubled between 1999 and 2007 and because two drugs had hit the market in 2011 that promised to cure many more people than was possible before. “Unless we take action,” CDC director Thomas Frieden said in a call with reporters, “we project deaths will increase substantially.”

Boger’s plan had come together: get to market with a breakthrough drug in time to wake up the government and the world to the fact that unless infected people get treated, they will develop serious liver disease, costing everyone dearly. In fact, it may have worked too well for long-term investors and some inside the company. By leading the industry across the threshhold to effective, direct-acting antiviral drugs against HCV and promoting the expansiveness of the opportunity beyond, Vertex emboldened competitors who, for the moment, seemed to be racing ahead, costing the company its dominance and forcing it to scale back its plans while exposing it to takeover threats for longer than it preferred or was healthy. Still, there seemed to be no question that Vertex’s aggressive, all-in scientific program and astute government lobbying had led the way in sparking a remarkable boon for patients, taking the world from one in which you had to suffer miserably for a year to have a 4-in-10 chance of being cured, to the likelihood in a couple of years of only having to take a few pills for twelve weeks for a 9-in-10 chance. Few areas of medicine have improved so dramatically in so short a time.

One problem, perhaps, of being a visionary leader is that once you’ve pried back the future, your vistas don’t just end. As much as you’ve advanced things, what stirs you is the next challenge, and you’re prone to be impatient and disappointed with a world that doesn’t keep up. So long as Vertex didn’t get taken out, Boger could content himself with its strategy in HCV. What worried him was its decision to be less brash in its public ambitions, to yield to gravity. Internally, the company still expected itself to do what others wouldn’t, or couldn’t, do, but as it presented itself to the Street, its arrogant insistence on being both exceptional and right seemed to be lost.

That’s always what we did. I was always accused of giving guarantees that I never uttered. People read their own narrative onto those: “Telaprevir is gonna be monotherapy, absolutely.” I was just painting you a vision of what the data said at the time. This is a possibility, and until it’s not a possibility, it’s a possibility. Why is that not the thing we still should be doing? It worked pretty damn well, and works pretty damn well for people that have high p/e ratios in other industries. Apple gets its high p/e ratio not because people have analytically projected out that they will control cell phones through 2020. That may be true, but why does Apple get that presumption? They get it because they take that ground. Apple doesn’t promise that ground. They just
act like that’s true
.

We don’t externally act like it’s true anymore. We don’t act like we have the best ideas in, say, JAK3 anymore. We get caught up in “Well, I can’t prove it. No, we have to get data.” That’s not inspiring. I think we’re in a perfect position. Don’t overpromise at all about HCV sales. Don’t even get into that conversation. Just keep blowing the numbers out. But absolutely be incredibly excited about all the things that are coming along. Why can’t those two live in the same world? I don’t know why we have to be similarly buttoned down on our research. Research is all about hope. It’s about possibility. It’s not about certainty.

As summer slouched into fall, Vertex approached the run-up to the Liver Meeting, back in Boston this year at the Hynes, as the next engagement in a long war of attrition. The memory of last year’s humiliation no longer stung. If Gilead or Abbott took away the company’s lead in hepatitis C in a couple of years, Vertex would find ways to cope. Cumbo stoked the morale of the sales team, which had the most to lose from an onrushing, interferon-free world. To motivate them to promote Incivek while the drug remained the standard of care—and to keep them from defecting—he negotiated a generous retention package, winning support from Smith and Leiden. Meanwhile, the company announced partnerships with GlaxoSmithKline and Johnson & Johnson to test VX-135—formerly Alios’s ALS-2200—with their antivirals. A disappointing
quarterly earnings report in late October dragged the stock price back into the low 40s. In the airwalk between JB-I and JB-II the company added a colorful new banner alongside the three Vertex values:
Patients First
.

The more things sped up and changed, the more they remained the same. Kauffman, after a brief respite from investor relations, plunged back in during the weeks leading up to AASLD, becoming once again the company’s incorruptible avatar, sanctifier of all data. Unlike Boger, he was immune to grandiosity. Asked by FierceBiotech’s Ryan McBride about the breakneck, roller-derby-like “rush toward pharma gold” in hepatitis C, Kauffman commented: “It’s not just crowded, but the speed of change I think is very unique. It’s really quite remarkable and we are very happy to have been at the forefront of this. Incivek paved the way for direct-acting antivirals.”