The Antidote: Inside the World of New Pharma (42 page)

As bacteria and detritus were swept increasingly from their lungs and airways, the patients on the drug had significantly fewer “pulmonary exacerbations”: debilitating setbacks of worsening sputum and cough, shortness of breath, chest pain, appetite loss, weight loss, and lung function decline often requiring long hospital stays. The unambiguous take-home message from the trial was that for the 4 percent of patients most likely to benefit from a potentiator, VX-770 was a dream molecule, something that gave them back their lives by fixing the underlying cause of what was wrong with them. Science fiction made fact.

Far more than the Vertex swoosh, the STRIVE results opened up new horizons and raised daring possibilities about the future both of the company and of medicine, forcing Vertex yet again to lunge ahead and grow swiftly to keep pace. Everyone around the table instantly felt the impact: here was another blockbuster to build out under, the second in less than a year, an unprecedented repeat performance driving toward another launch, most likely within the next twelve months. Organizationally and financially, the company now had to prepare—while still burning record amounts of cash and preoccupied with building out operations—to emerge in 2012 as a full-service, multiproduct, global biopharmaceutical company.

The launch of telaprevir, the singular goal around which the company had organized itself for six years, now morphed into something both larger and smaller. It remained the essential driver of Vertex’s near-term future, yet was diminished—if not dethroned—by the onrush of the next critical phase in the company’s evolution. Though the impending launch was all most people in the company cared or thought about, what now compelled senior management was not just to cure as many patients as possible and crush Merck but also to bring in enough revenue from telaprevir to propel Vertex high enough and fast enough to reach a kind of escape velocity—putting it on a trajectory toward long-term sustainability. “The first stage of a Saturn V rocket,” Emmens began to call it.

Bernstein’s Geoff Porges noted the shift. He, like a number of other analysts, believed that 770 would be rapidly approved, and he forecast, despite the small number of people who would take it, sales of $500 million or more a year. Porges knew the company could price the potentiator at more than $250,000 per patient per year, and that governments and health insurers would pay that much because they believed the benefits justified the costs and because the number of patients was minuscule compared with other diseases. (Some recent biologics for patients with rare genetic disorders were priced as high as $400,000 a year.) He also recognized the magnitude of the findings: that Vertex, miles ahead of any competitors, would redouble its commitment to discovering a cocktail that worked for the other 96 percent of patients and to striking hard against other genetic diseases while the whole area of personalized medicine heated up. After writing a note exhorting investors to buy VRTX and setting a price target of $80, he explained:

Hep C we’re going from a 35 percent cure rate to a 70 percent cure rate. That’s really impressive. Tens of thousands of patients are gonna benefit from that. It’s gonna save a lot of grief and cost in the future. That’s great. But cystic fibrosis. If you take cystic fibrosis from a universally fatal and life-shortening disease into a chronic illness—you’re on a lifetime of medication but you have a normal life expectancy, and that’s now feasible—that’s
breathtaking.

I think the body language inside the company has transformed from where it was six to nine months ago—because of CF. They viewed themselves the way the Street still views them today, that is, as a company that’s gonna have this short burst of fabulous profitability and maybe has a few other singles and doubles in its back pocket. The company inside now views themselves as having this short burst, and then having just this huge thing beyond that short burst. And the huge thing is this transformation of the most common inherited disease in our society.

Vertex shares rose 15 percent on the STRIVE data. Amid the ebullience in San Diego and Cambridge, there remained a nagging sense of
incompletion, especially among those working in CF, who could not feel that they had done their job until the great majority of patients had access to effective medicine. With two correctors, VX-809 and VX-661, advancing in the clinic, hopes at both sites remained high, but nowhere near as high as on Wall Street. “We got more reflective,” Olson recalls. “We thought, ‘Yeah, this is fine, the four percent. It’s almost like we’ve got the seed corn now. Now we know that plant has germinated, but to get more seeds, the whole thing’s gotta grow. We’ve shown we can grow corn from that seed, but we’ve got to grow a lot more ears.’ ”

More than twenty years earlier, when Francis Collins and his collaborators located the gene that causes cystic fibrosis—and then a decade after that, when the human genome was decoded, holding out the promise of a new epoch in medicine—no one could foresee the larger societal dilemma presented by an ultraspecific, ultralucrative superorphan small-molecule drug for a narrow genotype of patients. An estimated six thousand of the seven thousand known human diseases are rare, affecting as many as thirty million people total. Yet with industry giants like Pfizer shedding unprofitable programs and struggling to survive, the number of new medicines filed with the FDA dwindling in a year from thirty to twenty-two, and average drug revenues dropping, Porges’s bullishness introduced a new moral calculation.
Forbes
’s biobusiness chronicler Matthew Herper, writing about the STRIVE findings under the headline “A Big and Dangerous Day for Personalized Medicine,” asked:

If every drug is only going to work in a few thousand people, what then? One tough reality is that the new methods of studying genetic variation, which look deeply at the biology of relatively small numbers of people, are at odds with the way we’ve been thinking about drugs for years, studying common medicines like cholesterol drugs in thousands or tens of thousands of patients . . . What we’re set up for is a collision between genetics and large-scale studies, between innovation and cost, and between a vision of medicine that is struggling and one that is trying to create itself. It could spark lots of great new medicines for everyone. It could also be a giant mess.

Keith Johnson
knew
he was not on placebo. He was forty-two years old, an information storage specialist for a company in Manhattan, married and a father of two preschool-age girls. Since people with cystic fibrosis rarely live to middle age, he was an elder, an anomaly. Eighteen months ago, he developed a respiratory flu and his FEV1, which is measured by blowing into a plastic tube, dropped to 39 percent of normal—below the cutoff for severe airway obstruction and the point at which patients qualify for lung transplant lists. When Johnson was diagnosed in college with CF, he’d been told his life expectancy was just a few years. His older sister, Jennifer, also born with the disease, died at age thirty-six after receiving a double lung transplant. Even as he beat back his congestion with intravenous antibiotics and was able to raise his FEV1 into the mid-40s, he knew his breathing would continue to decline by 1 percent to 2 percent a year. He worried about how much more he could take.

What motivated Johnson to recover from his lung infection through late 2009 and early 2010—the fiercest months, as it were, of the health care war in Congress, when Republicans seized on the subject of end-of-life care and conjured a specter of “government death panels”—was the chance to participate in a placebo-controlled study of VX-770 in adults with two copies of the delta-F508 mutation, the largest subgroup of people with the disease. The 120-patient trial was the first to test whether the drug, by itself, might help the much wider majority of sufferers who don’t have a gating problem but instead whose CFTR misfolds so that sufficient protein never gets to the cell surface. The biological rationale was to fix whatever scarce active protein the patient had.

Johnson’s doctor told him she thought the drug “was a game changer,” he recalls, but he had learned not to raise his hopes. A guarded but intellectually voracious Northern California native, he is a skeptic by nature and training—stolid, medium built, with short gelled black hair, intense hazel eyes, and graying sideburns. Life with CF was endlessly grueling: up to two hours a day of breathing treatments alone. Every morning, he sat for an hour at his computer, taking pills and inhaling drugs and saline solution through a nebulizer. Then he tried to do some work while jacketed by a powerful pneumatic vest that rattled his lungs until he coughed
up three and a half ounces of mucus. A die-hard existentialist, he exuded a grim, weary resignation about his ordeal.

“This disease does not take a day off,” he says. “It’s very persistent. So as an
Art of War
type of thing, that’s your adversary. You have to match or exceed its effort if you want to win, and that can be mentally and physically very draining. If you’re going to live with CF and get what you can out of life, you have to be realistic about things. If you wake up every day disappointed that you didn’t run a marathon, I don’t think you’re in the right place mentally.”

Johnson and his family rented a town house near the Hudson River in Westchester County. He played in a pickup weekend soccer game, usually becoming too winded to run during the second half, walking the field, bent, tugging at his shorts, gasping. He loves golf, struggling a couple of dozen times per year around Hudson Hills, the premier local public course. On the day in February 2010 that Johnson started taking two unmarked tablets daily, along with his usual treatment regimen, as part of the randomized sixteen-week study, he “blew” 52 percent. A patient’s FEV1 can easily vary from day to day; Johnson’s baseline for the trial hovered in the low 50s.

The second week in March, on a warm afternoon, Johnson played Hudson Hills with a friend. The eighteenth hole is a 403-yard par four. Climbing to the green after slicing his drive, when normally he would be “huffing and puffing,” he had little trouble breathing. “I felt amazing,” he says. “I felt cured. I hadn’t allowed myself to think that anything like this was possible. I could not believe that someone had figured this out.” A few weeks later, he blew 58 percent. When Johnson returned to the adult unit of the CF center at Beth Israel Medical Center in Manhattan, one of several study sites, at the end of June, he was tested again. His FEV1 measured 60 percent.

“I knew it when I blew it,” he recalls. “I could just feel. Within ten days, I would say that my life turned upside down for the positive. Not only did I feel that this was working, but that this opens up a whole new life, one that I wanted but that I hadn’t allowed myself to hope for because I just didn’t want to go through the disappointment.

“I was seeing everything completely different—at work, the possibilities.
It was the most productive time ever for me workwise. I never made as much money. I was winning every deal. The guy I work with said, “Dude, what is up with you? I can’t even keep up with you when we walk around the city.’ I couldn’t wait to wake up in the morning, to live life.”

Keith and his wife, Adrienne, had avoided discussing the future; the subject was too frightening. They had backed into family life without sharing any larger ambitions for how they hoped to live. Adrienne had wanted children; Keith, like most men with CF, was sterile. Yet they had found a doctor who reasoned that since his CFTR malfunction was in the vas deferens, the tube that transmits sperm to the ejaculatory ducts, Keith might have what he calls “swimmers,” and after eight attempts at extracting cells from his testicles and using in vitro fertilization, he’d become a biological father—twice. Still, the couple had never really looked ahead. “Life was like you were living from paycheck to paycheck, not in a monetary sense but ‘How Keith was feeling,’ ” he explains. “Not reliable. It was not reliable to make plans.

“Adrienne and I completely recalibrated our conversations. What is it that we can accomplish in life now? Moving into a better school district? Getting a second car? We were actually making plans.”

After the sixteen-week comparative study was completed, subjects who met prespecified criteria were eligible for an “open-label extension” or rollover; that is, everyone who wanted to continue on the drug was given free multimonth supplies, pending the outcome of the trial. Johnson recalls signing for boxes of VX-770 and greedily stuffing them into his backpack. His company was sold at a premium after a bidding war between Hewlett-Packard and Dell, and he and Adrienne started looking at split-level houses in Irvington, New York, near a school with an excellent reputation. He started showing up both weekend mornings for soccer, exercising so much that he lost weight—a curious anomaly, since his digestion was the best it had been in decades. “My exercise tolerance was so high, I was finding any excuse I could to do any type of cardio.”

Johnson blew 62 percent in November. He took his doctors out to celebrate. He and Adrienne bought a house, making a deposit with the proceeds from his stock options, but had no money left for living room furniture—the “Gift of the Magi” room, he called it. His daughters,
Claire and Danielle, called it their indoor soccer field. He began, in a dream, to feel unchained from the rigid sense of responsibility that he could never miss a treatment. “You know what?” he says. “I could miss a TOBI [tobramycin, an inhaled antibiotic for treating pseudomonas infection]; I could miss an albuterol. I could go out at night and come home and not do my meds. And it was not being irresponsible. It was just this freedom. I . . . I just couldn’t believe it. It was just so powerful.”