It would have been just another midsummer day of activities and camaraderie at church camp, except that Colin English hadn’t felt right since he rolled out of his bunk bed.
His legs had felt weak, and at first he couldn’t move them. Only with the help of campmates did the 12-year-old make his way to a morning assembly, walking hesitantly until he abruptly stumbled and fell.
“My legs just stopped working,” he recalled.
He couldn’t know in that moment, a year ago July, what had struck him. But his parents had reason to fear, and soon Colin would, too.
It was his turn.
After months of tests, he would be diagnosed with spinal muscular atrophy, the leading genetic cause of death in infants — and the disease that had killed his two sisters. Taleah died two days before her fourth birthday when Colin was a toddler; Tabitha succumbed eight years later at the age of 5. Their memory, and loss, haunts the family.
Colin had a less severe form of SMA. Most with the worst form die before age 2, never able to sit up and progressively robbed of the ability to eat and, finally, breathe. The condition attacks the neurons that control muscle function, and its course is inexorable.
But for Colin, there was reason for hope.
There had been no effective treatment when Taleah and Tabitha were stricken. SMA was a so-called “orphan” disease with too few cases — about 10,000 nationally — to draw the interest of biopharma firms that must balance research and clinical costs against potential financial gains.
But all that has changed. Scientists now have the gene-manipulating tools to devise drugs to attack these sorts of inherited diseases, one after another. Also, there is a business model to sustain their work — one built around sky-high prices. Boston’s booming biomedical sector is at the epicenter of this wave of miraculous new drugs and new drug companies.
For Colin English, the magic potion was called Spinraza. The injectable drug, sold by Cambridge biotech giant Biogen Inc., had taken more than a decade to invent, perfect, test, and bring to market. A key contribution came from University of Massachusetts Medical School in Worcester, where researchers discovered a way to target the disease.
The drug, approved two days before Christmas last year, had demonstrated in trials that it could stop the decline of many patients with SMA and reverse it in some; even children who had lost the ability to hold their heads up or work their arms and legs regained some movement.
“These kids were getting stronger,” said Dr. Basil Darras, a prominent neurologist who tested Spinraza at Boston Children’s Hospital. “We had patients who started sitting, and then standing.”
But just as Spinraza is the story of this new age of invention, bringing hope where there was none, it is also the story of the shadow that follows that dream. These drugs can be hard to obtain, no matter how desperately needed; the Englishes’ quest for Spinraza took many months and they would travel some 2,400 miles from their home in Orem, Utah, to Massachusetts General Hospital for the tests that would help qualify Colin to receive his first dose.
And these remarkable medicines often carry a stunning price. Spinraza costs $750,000 per patient in the first year alone, a sum large enough to give any insurer pause. Hundreds of drugs likely to command similarly stratospheric pricetags are in development or headed to market. The era of the $1 million drug is right at hand.
Is this a future that American medicine can afford? Can we afford not to?
In business, numbers talk: more customers, more revenue. So for years, traditional drug makers didn’t spend much time or money on diseases that affect relatively few people. They focused on volume, selling as many drugs to as many people as possible. That meant taking aim at conditions that affect millions, like high blood pressure, cholesterol, and depression.
But the restless innovators in the modern biotech sector were turning their eyes elsewhere, to the potential for cures – and profits — in medicines for rare and extremely rare diseases. The scientific foundation for this work lies in the Human Genome Project, an international research effort to map the genes of all human beings that started in 1990 and was completed in 2003. That project provided clues to the sources of some long-untreatable diseases — and, with them, a roster of attractive genetic targets for drug makers.
The sea change that made rare diseases a winning business proposition dates to the early 1980s when — prodded by the mobilized families of desperate patients — Congress passed the Orphan Drug Act. The act, which President Reagan signed into law in 1983, gave companies major incentives to develop drugs for conditions that affected no more than 200,000 Americans. The inducements included giving companies tax credits and the exclusive right to market their new drugs for seven years.
The strategy worked. Before 1983, only 34 orphan disease drugs had been approved in the United States. Today, more than 650 have won approval. There are an estimated 7,000 rare diseases that, all told, affect roughly 1 in 10 US residents.
And the pipeline of new treatments is gushing. Biotechs are developing more than 560 medicines for rare diseases, according to a 2016 report by the Pharmaceutical Research and Manufacturers of America and the ALS Association.
Nowhere has this cyclone of innovation been more powerful than Massachusetts, with new firms built around new ideas popping up all over. Massachusetts is home to the nation’s largest biotech cluster. To cite just a few local drug-development projects:
A Cambridge biotech company is experimenting with a technology called gene silencing to treat rare diseases passed on through families, including an enzyme deficiency some historians believe caused the mental breakdown of King George III.
Down the street, another biotech is developing gene treatments for sickle cell disease, a blood disorder that in the United States afflicts mostly African-Americans. Ten miles west in Lexington, a company is working on a gene therapy for Huntington’s disease, the neurodegenerative disorder that killed folk singer Woody Guthrie.
All of these drugs, if approved, are sure to carry massive pricetags.
In just over a year, the Food and Drug Administration signed off on a string of drugs with annual prices that rival the cost of a well-appointed house in the Boston area. Several of the drugs have roots in Massachusetts biotechs and the state’s esteemed teaching hospitals.
Among the new medicines is Exondys 51, approved by the FDA in September 2016 as the first treatment for children with Duchenne muscular dystrophy, a lethal disease. Its maker, Cambridge biotech Sarepta Therapeutics, said the average price of Exondys 51 is $300,000 a year, but since dosing is based on weight, some experts say it can cost far more.
And then, of course, there is Spinraza.
Like thousands of other US families whose children have SMA, the Englishes were elated last December when they learned the Food and Drug Administration had at last approved Spinraza.
Elated, and also heartbroken.
“I was so happy for my friends who had children with SMA,” Monica English, Colin’s mother, said. “But I took an hour or so to cry that it wasn’t there for my girls. . . . When my daughters were diagnosed, [doctors] said, ‘Take them home and make them comfortable.’ ”
For Colin, as for his parents, the prospect of an effective treatment marked the beginning of a new chapter in a household where the specter of SMA was always present. He knew his sisters had died as little children. They were sweet pictures on the wall, the baseline of a family story that extended to his brother Jaxon, who is also at risk for the disease but has so far showed no signs of it, and his father, who is a genetic carrier but also has a gene that protects him from its ravages.
When Colin was 7, doctors took skin samples from him and other family members to study their genetics to help unravel the mystery of SMA. “We all have matching scars on our arm,” said Monica. “He would ask me about it every year. He would say, ‘Mom, did it make any difference that they took my skin? Did it help anybody with SMA yet?’ ”
By the time Colin had grown into spirited adolescence without showing signs of SMA, the Englishes dared to hope that he too carried the same blocking gene that kept his father from developing symptoms.
His fall at camp had dashed that hope. But Colin’s SMA is a slower-progressing, less devastating variant than the one that killed his sisters.
Now a remarkably even-keeled eighth grader with dreams of becoming an astrophysicist, Colin said his symptoms gradually intensified after his legs gave out on that day in the summer of 2016. He took a hard tumble last spring while walking in a park with friends, and fractured his arm trying to break his fall. He could no longer run, and at school he had to use an elevator because of fears he might fall on stairs.
Clearly, if Spinraza could halt his decline, he needed access to it quickly. That would prove much more difficult than they could have imagined.
It was a race against time.
The joy that came with the revelation that there was finally a treatment for SMA was quickly subsumed by sticker shock.
Biogen said it would charge $750,000 per patient for the first year and $375,000 annually after that. Although families weren’t going to have to come up with the money themselves, someone would have to; alarm bells were soon ringing at health insurers nationwide. Some moved swiftly to restrict coverage based on age or the severity of a patient’s condition.
Still, demand for the drug quickly overwhelmed health care providers. Many weren’t prepared to administer it, or to navigate the complications involved in testing patients to determine whether they were candidates for treatment. Hospitals, many of which had to buy Spinraza up-front before seeking reimbursement, weren’t sure whether insurers would pay — and some balked at the prospect of getting involved with the new treatment.
And so, despite clear promise of the drug and the life-or-death stakes for SMA patients, the growth in the number of sites offering Spinraza injections was — and remains — agonizingly slow. There are now about 80 sites accepting new patients, according to Kenneth Hobby, president of the patient advocacy group Cure SMA. All told, about 180 hospitals and clinics around the country are administering Spinraza, though few are in rural areas.
People with SMA have faced long waiting lists and mountains of paperwork.
Ben Gabelman, a 27-year-old from Atlanta who is being treated at Mass. General, said it took six months of phone calls and applications before UnitedHealthcare and Biogen itself agreed to cover his Spinraza treatments.
“It was a second full-time job just for me to get the approvals, and the struggles cannot be underlined enough,’’ Gabelman said before getting his second dose in September.
He was one of the fortunates. Nearly a year after Spinraza’s launch, fewer than 15 percent of SMA patients in the United States have been treated.
Where the drug is offered, the crush of patients is overwhelming.
The clamor for Spinraza “basically shut down our whole office from December to March,” said Dr. Kathryn Swoboda, a veteran neurologist who set up Mass. General’s SMA program and tested Colin English. “There were so many calls [and] our own patients couldn’t get through because there was such a desperate need for this therapy.” One family flew from Chile to Boston the day after Christmas, arriving at her office without an appointment.
None of these fears and frustrations are unique to Spinraza. They are the growing pains of a new era of biopharma — and of unexpected hope.
The Englishes had wanted Colin treated in Utah so as not to disrupt his sixth-grade year in school, but the local hospital at first limited Spinraza injections to children with the most severe form of SMA. Their dealings with their insurer, Cigna, also dragged on in a draining, frustrating way. Then finally, about eight months after Colin’s diagnosis, came the answer, and Monica English remembers the moment vividly.
She was walking on the campus at Utah Valley University, where she is a student, when she took a call from a caseworker with good news.
“I screamed right out loud,” she said. “It echoed, and everyone could hear it.”
Biogen acknowledges that most SMA patients are not yet receiving Spinraza, but it says that is not unusual for a new specialty drug. “Early launches are always bumpy,” said Caren Deardorf, the company’s global brand leader for Spinraza.
But Biogen is not at all apologetic about the drug’s extraordinary price.
Company executives describe Spinraza as a medical breakthrough, one that was a deeply moving moment for those on the Biogen team who shepherded the drug through late-stage clinical trials and saw patients improve unimaginably.
“It’s once in the lifetime. . . that we have the opportunity to launch such a product that is basically the first hope for those patients,” said Biogen chief executive Michel Vounatsos.
In setting Spinraza’s price, Biogen executives said, they considered the drug’s value to patients, its benefits to the health care system, and the company’s need to fund work on other experimental medicines. That includes five drug candidates for Alzheimer’s disease in the development pipeline. “Not all of them are going to work,” said Biogen’s Deardorf. “We want to be able to stay a viable entity so that we can get to Alzheimer’s.”
Beyond that, they say, the $750,000 first-year cost of Spinraza looks more daunting than it is, because new patients must take four “loading doses” in the first two months. The subsequent cost— $375,000 annually — is in line with that of other rare-disease drugs, they say.
The executives may be right, but that does nothing to ease the strain these super drugs are putting on the health care system.
“We’re going to reach a breaking point,” said Michael Sherman, chief medical officer for the insurer Harvard Pilgrim Health Care in Wellesley. “In five or 10 years, we’re going to run out of the ability to pay for these drugs.”
Massachusetts has much at stake in this race between cost and cure, but the ripples will be felt more widely.
Spinraza arrived amid a growing backlash against rising drug prices, underscoring the lack of consensus on how to pay for these cutting-edge medicines and spotlighting the deep divisions among drug makers, insurers, physicians, and other parties throughout the health care system.
Industry critics are calling for an overhaul of the way drugs are paid for in the United States. They span the political spectrum, from President Trump to Senator Bernie Sanders of Vermont. Among other measures, the critics have called for requiring drug makers to disclose data to justify costs and letting Medicare, the US agency that insures older and disabled Americans, negotiate prices directly with manufacturers.
Unlike most other Western countries, the United States does not dictate the cost of prescription medicines. But in October, the new FDA commissioner, Scott Gottlieb, declared that high drug prices are “a public health concern that FDA should address.” That marked a potential break with the agency’s history of focusing solely on the safety and effectiveness of medications.
Ezekiel Emanuel, a bioethicist who chairs the medical ethics and health policy department at the University of Pennsylvania, said the first-year cost of Spinraza is more than 13 times the median US household income. “It’s hard to see how it can be justified,” he said.
Spinraza is the latest fruit of a successful business strategy that has made Biogen the largest biotech based in Massachusetts, with a market value of nearly $70 billion. The company earned a profit of $1.3 billion on sales of $3.1 billion in the three months ended Sept. 30, with Spinraza accounting for a chunk of those gains. Last month, Biogen for the first time disclosed the number of patients who have received Spinraza injections in the United States: nearly 200 in clinical trials and about 1,200 since approval.
Still, the Spinraza ramp-up has been weaker than stock analysts anticipated.
Biogen’s share price dropped in late October when it posted Spinraza sales of $271 million in the July-to-September period, falling short of Wall Street expectations. Executives said sales growth slowed in part because early US patients had moved from loading doses to less frequent maintenance doses, generating less revenue. Also, they said, Biogen has been providing the treatment free to about 20 percent of patients not in clinical trials, under a support program intended to help those who can’t get — or haven’t yet gotten — insurance approval.
The balance between the expectations of patients and of the marketplace is hard to strike, and will only get harder as more genetic mysteries are solved and more remedies are held out to those in desperate need.
“Medicine is changing,” said Peter Saltonstall, president of the National Organization for Rare Disorders, a Quincy-based advocacy group that helps patients obtain gene-based therapies. “Science has grown faster than insurance’s ability to adapt to the [new] system.”
Before she took her talents to Mass. General, Dr. Kathryn Swoboda worked in Utah. That’s where the Englishes came into her practice and she into the family’s life.
She had headed west in 1998 after completing her training in neurology and genetics at Boston Children’s Hospital, bringing with her a fascination with SMA. Utah was a draw in part because of the chance to study the genetics and health history of the many large Mormon families there, like the Englishes (though they have since left the church). She launched a database of SMA cases, looking for patterns.
Taleah English was the seventh SMA patient she saw in Utah. The child was just three months old, and there was little the doctor could provide but empathy.
“At the time, we had nothing to offer these families,” said Swoboda, an Ohio native who brings a palpable if quiet intensity to her work. “If the babies presented [with symptoms] before six months of age, there was a good chance they weren’t going to see their second birthday.”
Monica English wasn’t going to accept that.
“She said, ‘I just want more time with my daughter,’ ” Swoboda recalled. “She wouldn’t take no for an answer.”
The family did get a little more time. The doctor, whom Monica English calls the family’s “guardian angel,” was with them on that summer day in 2004 when Taleah died. Swoboda lifted the young girl up, hugged her, and gave her a kiss on the cheek. Years later, she was also there to say goodbye to Tabitha.
By the time Colin was diagnosed, the doctor had spent nearly two decades studying the family’s genetics, looking for clues that might solve the puzzle of SMA. The Englishes were a particularly intriguing subject, given their shared history of the disease in its variations and degrees of severity.
Some notable discoveries came from Swoboda’s work. Collaborating with German scientists, she discovered that John English and two of his siblings, while testing positive for SMA, have the rare modifier gene that protected them from developing symptoms. The researchers were the first in the world to discover that modifier gene.
Swoboda was at Mass. General early this year when she learned Colin had begun showing symptoms. He needed to quickly get into the queue for Spinraza, so she stepped into action.
She used a National Institutes of Health grant to fly the Englishes to Boston in July so Colin could undergo the testing needed to convince Utah doctors and Cigna that he was at high risk of progression. During that trip, the boy continued to fall sporadically, sometimes in the middle of busy Boston streets.
Although more SMA patients lately have been getting coverage, many regional — and some national — health insurers continue to reject covering patients with less severe forms of the disease, citing insufficient data. Others have yet to come up with a formal policy, weighing applications case by case. Fewer than a dozen state Medicaid plans have posted Spinraza policies. Many of those that do have set limits based on age and disease type.
Doctors have also found themselves on the front lines in pressing insurers. In addition to appealing denials of coverage, they must deal with insurance company requirements for periodic testing of patients to verify they are making progress.
“I’m worried more and more about these denials, and the continuation of [coverage for] the patients who are being treated,” said Dr. Gyula Acsadi, a neurologist at Connecticut Children’s Medical Center.
Acsadi recalled a particularly frustrating consultation with Cigna over his appeal of its rejection of coverage for a teenager with SMA. The insurer’s own medical directors agreed the drug could help the boy, Acsadi said, but Cigna still wouldn’t pay. According to Acsadi, the insurer’s medical specialists instead suggested that the neurologist contact Connecticut lawmakers and ask them to put pressure on Cigna executives.
The company didn’t respond to a request to discuss the case.
Resourceful patients are nevertheless finding ways to obtain Spinraza, even though it can be exhausting for people coping with a serious illness.
Jen Peters earlier this year made nine round-trips from her home in Omaha to St. Louis Children’s Hospital, where her two children, 7-year-old Ella and 4-year-old Grayson, received Spinraza. It’s a seven-hour drive each way. In October, they finally were able to get the drug at Omaha Children’s Hospital and Medical Center — a 10-minute drive from Peters’s home — which had taken months to get its program up and running.
“It’s a lot of time, money, travel,” said Peters, who spent a night in a hotel each time before returning home. “And it’s not easy to travel with two children in a handicapped van.”
Mary Bodzo, who grew tired of waiting for her Gainesville, Fla., hospital to treat her 28-year-old daughter Krista, regularly drives five hours to a hospital in Phoenix City, Ala., where Krista gets injections. “It’s maddening,” Bodzo said. “There have been so many roadblocks and so much red tape. . . . . I didn’t know that in this country, in 2017, something like this could happen.”
Carrie Cowgill, 55, gets up at 4 a.m. at her home in Boise, Idaho, so her adult daughter can drive her to Salt Lake City for 10:20 a.m. injections. A single mother with two grown children, Cowgill works in building services for St. Luke’s Hospital System in Boise, Idaho.
St. Luke’s, her employer, decided against offering Spinraza injections. Cowgill’s health insurer, Select Health, said it wouldn’t pay for drugs not being provided by the hospital. She is receiving the drug for free through Biogen’s patient support program.
Cowgill said she’d like to be treated in Idaho, though she made five trips to Utah and will continue to if there’s no other option. The drug has allowed her to resume activities she had been forced to abandon, including swimming and riding a recumbent bicycle.
After her first Spinraza injection, Cowgill said, “I felt better within two days. My arms felt lighter. I was able to stand up longer and curl my hair over my head.”
That, she said, is “something I hadn’t been able to do for some time.”
Even after Cigna approved Spinraza for Colin, the English family’s ordeal was hardly over. The insurer demanded he first undergo another round of evaluations, including physical therapy and tests of his muscle tissue.
The celebration would have to wait, even as another sort of celebration went ahead. On Sept. 5, the entire English clan gathered in Vineyard Park near their home in Utah to celebrate the birthdays of Colin and his brother Jaxon. Every such day is a gift in a family that knows how easily life can be cut short.
After the party ended, the waiting resumed. When would Colin be able to get a dose of Spinraza? Days and weeks were ticking by, his condition worsening. He had to rely on a walking stick for support when he visited a friend’s home.
Finally, on Oct. 19, Monica drove Colin to Primary Children’s Hospital in Utah for his first treatment. “He was excited and nervous all at the same time,” she said. Nurses gave him nitrous oxide to ease the jitters.
Even there, in the treatment room, there was a delay. Because the drug is so expensive, the hospital’s policy is to keep it in a cooler until patients arrive. An hour passed before the medicine was warm enough to administer.
Colin has since received three other loading doses, the final one just this past Thursday. The next injection is scheduled for April. He and his family are optimistic that Spinraza will improve his mobility and prevent him from falling. In some patients, the drug’s effects can take longer to become evident. The Englishes are again waiting, still drawing on that reservoir of hope that has yet to go dry.
“We’ve seen the worst, and this is not the worst,” Monica said. “It’s something we’re dealing with.”
Robert Weisman can be reached at email@example.com. Follow him on Twitter @GlobeRobW. Jonathan Saltzman can be reached at firstname.lastname@example.org.
Video produced by Scott LaPierre/Globe Staff