Early success stories like these from medical centers in Boston or Stanford or the NIH are wonderful, but have little relevance for the millions of sufferers in Africa, where the impact of SCD is felt the hardest. In October 2019, the NIH and the Gates Foundation announced a $200 million program over four years to produce affordable therapies for patients in Africa. The goal, Collins says, is “to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries.” But he readily admits: “This is a bold goal.”26
In her final year at college, Shani Cohen gave birth to her first child, a beautiful baby girl named Eliana (“God has answered me” in Hebrew). Around eight months of age, Shani noticed that her daughter couldn’t stand up in her crib like other infants her age. Eliana was eventually diagnosed with SMA type 2, often called “floppy baby,” caused by a mutation in a gene called SMN. Shani was devastated, the only silver lining being that type 2 is not the most severe form of SMA. The motor neurons die, leaving patients basically paralyzed, many dying of respiratory failure, often before their first birthday. “Think of it as ALS [amyotrophic lateral sclerosis] but in infants,” said Sean Nolan, the CEO at the time of AveXis.27
For Jerry Mendell, success treating patients with SMA and other forms of muscular dystrophy finally came after two decades of persistence. Following the Gelsinger tragedy, he built a group at Nationwide Children’s Hospital in Columbus, Ohio, and set about developing new AAV vectors. In 2008, his colleague Brian Kaspar reported success with a newly engineered virus called AAV9 that had traversed the blood-brain barrier in mice.28 Following more encouraging results in monkeys, Mendell believed they were ready to begin a clinical trial, but no drug companies wanted to take the risk. Kaspar cofounded his own company called BioLife (later renamed AveXis), and licensed the rights to Mendell’s SMA program. But the high AAV doses required to ensure delivery to all the affected tissues, including the diaphragm and the heart, had experts worried. One even warned Kaspar: “You’re going to kill someone—this is going to be Jesse Gelsinger all over again.” Mendell wasn’t about to stop now. “I’m sick of watching kids die,” was his justification.
Mendell’s trial launched in 2014 with fifteen children; within a few weeks, he saw an unwelcome spike in levels of liver enzymes in the first patient—warning signs of inflammation or liver damage. After consulting the FDA, Mendell changed the trial design, administering steroids before the gene therapy. Most complications disappeared. As reported in 2017, all patients showed rapid increases in motor function attributed to elevated levels of the SMN protein.29 Most of the children can now sit unassisted, an unprecedented result. “What used to be called a science experiment, gene therapy, is becoming a reality,” Nolan said, narrating a video of an SMA child sporting a Spider-Man backpack skipping out of hospital unaided. One of Mendell’s first patients was Evelyn Villarreal, whose younger sister Josephine died before the therapy was available. At age three, Evelyn is dancing, doing pushups, and enthralling Senators and staffers on Capitol Hill.
The SMA success story proved irresistible to the Swiss pharma giant Novartis, which acquired AveXis for $8.7 billion in 2018. Zolgensma became the second FDA-approved gene therapy drug in May 2019, but how would Novartis price a potential one-time therapy? CEO Vas Narasimhan had hinted the price could be as high as $5 million. In that light, the final “responsible” list price—$2.1 million—seemed almost reasonable, but Zolgensma still claimed the dubious title of “the world’s most expensive drug” in history. Even the SMA trade paper seemed taken aback: “At $2.125 million, a 60-minute intravenous infusion of Zolgensma costs more than a 2,000-square-foot apartment in Paris with a view of the Eiffel Tower, a brand-new 2019 Aston Martin One-77—among the fastest cars ever made—or a Cirrus Vision SF50 private jet.”30 Novartis allows patients to defray payments over five years, and will offer some sort of money-back guarantee if, for example, the patient dies.
Most experts however felt the exorbitant price was justified: it fell within the guidelines set by the Institute for Clinical and Economic Review, a drug pricing nonprofit, and it could work out cheaper than the full course of a rival drug, Biogen’s Spinraza, over five to ten years. In Novartis’s case, the price had to recoup not only the cost of developing the therapy—an estimated $550 million—but the billions of dollars to acquire AveXis. While there are 10,000–20,000 SMA patients in the United States, there are only about seven hundred children under two years of age, the cutoff for Zolgensma approval.
SMA patient groups welcomed the drug’s approval as priceless. Nathan Yates, an economics professor who suffers from SMA, declared there should not be a price tag on life. He thought of his parents receiving the devastating news that their child has SMA and that there is no cure. “The price of Zolgensma seems insignificant now, don’t you think?”31 It wasn’t to the parents of Eliana Cohen. Shani and her husband Ariel despaired as their health insurer denied coverage for Zolgensma and spurned their appeals. With Eliana’s second birthday just a week away, the Cohens launched a desperate crowdsource campaign. Miraculously, they raised $2 million in just five days.
On Maundy Thursday 2019, the New England Journal of Medicine published a study in which a team at the St. Jude Children’s Research Hospital in Memphis, Tennessee, successfully treated eight infant boys with “bubble boy” disease (X-linked SCID), the same disorder that Alain Fischer had treated two decades earlier.32 “We believe that the patients are cured,” said team leader Ewelina Mamcarz. “They’re living normal lives, and they have normal, functional immune systems.” They had returned home, were starting daycare, and making antibodies in response to vaccines.33 The results were hailed as a complete fix for these patients, although investigators would be monitoring to ensure there were no adverse effects. “The data are extraordinary for every single patient,” said Manny Lichtman, CEO of Mustang Bio, which licensed the rights to the therapy. But how will patients’ families afford MB-107, which is designed to be a one-time treatment? Lichtman suggests a deferred payment scheme over a period of about ten years (assuming the therapy still works).
Gene therapies are expensive to develop and to manufacture, and the biotech companies that take the risks to develop these drugs deserve to recoup their investment. Skyrocketing prices are happening across all areas of the pharmaceutical industry, not just gene therapy. To address the soaring cost of drugs for rare diseases, some economists have floated the idea of healthcare loans, or “mortgages for medicines.”34 It is not clear whether current economics will sustain gene therapies and genome editing treatments. The arrival of new, improved therapies should lead to stiffer competition and reduced prices, but in practice, precision medicines and reformulated generics often justify higher prices. “Certainly, there must be a price that is too high,” said philanthropist John Arnold. $5 million? $20 million? $100 million? “How should society answer that question?”
“I don’t want my legacy to be the most expensive drugs in history,” George Church told me. “We’ve brought down the price of the genome from $3 billion now to ‘zero dollars.’ That I’m proud of. I’m much more excited about that than I am about my contribution to expensive therapy.”35 This is not scalable. Five percent of live births have a Mendelian genetic disorder—the long tail of thousands of rare or orphan diseases. “We’re not going to be spending $2 million on 5 percent of births!” Church says. He estimates that the total cost, including opportunity losses and caregiver costs, is a catastrophic $1 trillion worldwide per year, not to mention the collective pain and suffering.