Noel Ölyüs with his family. He has a genetic disease called spinal muscular atrophy and has been entered into a lottery in hopes of getting a potentially lifesaving drug.

A lottery like no other offers up a cutting-edge medicine — with lives on the line

The lottery that began this week was not about money, or about choosing a school, or about obtaining a visa. It was about a child’s life.

In this case, the children selected would receive a drug that otherwise was not available. Jamie Clarkson, an electrician in Queensland, Australia, entered his 18-month-old daughter, Wynter.

“We applied for it because we desperately want this drug for our daughter, but you’re putting your daughter’s well-being and longevity in the hands of a lottery,” Clarkson said. “I guess it’s the fairest way to decide who gets the drug and who doesn’t, but yeah, it’s not a great feeling.”

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The treatment, a gene therapy called Zolgensma, is designed for children like Wynter who have a neuromuscular disease called spinal muscular atrophy, or SMA. Without it or other treatments, those with the most serious type are likely to die as babies. It was first approved by U.S. regulators only last year, and is not yet available in other countries.

The lottery was devised by the drug’s manufacturer, Novartis, to give families in those places a chance to get it through a novel form of compassionate use — a way to get medications that have not been approved — while they wait. Fifty doses are slotted to be given away for free in the first half of the year, with up to 100 total.

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The first drawing occurred Monday.

Ethicists and advocates have debated the merits and the design of the unusual arrangement. Parents said that it was uncomfortable to cast their child’s fate into what felt like a sweepstakes — a kind of bizarre Willy Wonka contest in which, as Maura Blair, a Canadian mother of a child with SMA put it, “we’re talking about lives.” But if it was a chance to get the drug, it was worth trying.

Zolgensma costs $2.1 million in the United States — the world’s most expensive drug. And even if it is to cost less in other countries, even if it is to be covered by insurance, infants at this point are not eligible for it after turning 2. Some families have even tried to fundraise in hopes of buying the drug themselves and getting it injected by doctors in the United States.

“She’s 7 months,” Laura Silva, who lives north of Toronto, said about her daughter, Rebecca. “Do we rely on their word and wait it out? Or do we take action ourselves? Because the sooner she can get it, the better for her.”

Some parents said they had taken issue with news coverage of the lottery, which has framed the eventual recipients of the drugs as “lucky winners.” If that were the case, what did that say about everyone else?

The kids appeared healthy at birth. But soon, their parents recalled, it became clear that something was wrong. They couldn’t raise or control their arms and legs. They would choke on their milk.

Jamie Clarkson, in Australia, said he and his wife, Kellee, had a friend with a daughter around Wynter’s age. When laid face down (“tummy time,” in parental parlance), the girl had no problem lifting her head.

“The difference was chalk and cheese,” he said. “Our girl sort of laid there and didn’t do anything.”

Sometimes the parents were told their kids just needed more time, but eventually, a clinical evaluation and genetic test would confirm the SMA diagnosis. The most serious form, called type 1, is estimated to affect 1 in 15,000 babies.

Wynter Clarkson Courtesy Jamie Clarkson

Children with the disease have a mutation in a gene called SMN1 (or a missing gene) that meant cells don’t produce sufficient SMN protein. The dearth of the protein debilitates motor neurons, which are responsible for relaying messages to muscles, and creates a cascade of issues that culminates in muscle weakness.

Without treatment, babies with type 1 SMA might never be able to lift their heads or arms or legs, and struggle to regulate their swallowing and breathing. Most die by 2, typically because of respiratory issues.

Zolgensma works by ferrying a healthy copy of an SMN gene into motor neurons — restoring production of the protein and the health of the neurons. It is a one-time treatment with lasting benefits — like reigniting a pilot light.

When Zolgensma won approval from the U.S. Food and Drug Administration in May, it was hailed a monumental victory for families and an achievement in genetic medicine — one of the first gene therapies to make it to the market. But it also created a divide between haves and have-nots — American parents, assuming insurance companies would cover the treatment, and parents anywhere else in the world.

It is not uncommon for a drug to be available in the United States before other countries; drug makers routinely apply for and receive regulatory clearance from agencies around the world at different times. But the FDA’s approval drove global appeals for a drug that offered babies a chance.

Beyond the issue of regulatory approval, supplies of Zolgensma are tight, Novartis has said. Gene therapies are complex to manufacture, and the company only has one facility producing the drug right now, with plans for two more to come online this year. It also needs to have doses available for U.S. patients and for patients in other countries where the drug could become available in the coming months. (European regulators are expected to decide on Zolgensma this quarter, and Japanese officials before the middle of the year, the company has said. Decisions in Canada and Australia may not come until 2021.)

Novartis saw a lottery as the answer.

Random lotteries are an accepted way to mete out resources when there is a limited amount, some ethicists have argued. They establish an equal playing field and remove the possibility that those with money or connections can maneuver to jump the line.

But experts have also questioned whether Novartis has done enough to try to overcome the scarcity issues. Some have also said that favoring those with the greatest need — meaning the sickest children — would be a more ethical approach; patients who are healthier could potentially wait until the drug is approved in their home countries or until more supply is available.

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“If it is really not possible to help all who are in need of help, then a lottery with priority to patients who are worst off is not a bad approach — and definitely fairer than other things a company could do,” said Holly Fernandez Lynch, a bioethicist at University of Pennsylvania’s Perelman School of Medicine. “The key is to first do everything possible to minimize the need for a lottery at all — and it’s not obvious to me that Novartis has done that here.”

The fact that the lottery created a situation in which there are, for lack of better descriptors, winners and losers also left some people uneasy.

“You can’t do anything to improve your chances,” said Genevieve Kanter, also a bioethicist at Penn. “But it does become a zero-sum game, which is what bothers some people about the mechanism, even if at the end of the day, more kids get treated than in the alternate scenario where there’s no lottery.

“It’s the price we have to pay to have some kids treated.”

In an interview with STAT, the president of AveXis, the Novartis unit that developed Zolgensma, said the company considered prioritizing the patients who were sickest or those for whom another SMA treatment did not help. But the company, which is using an outside party to handle the selection and brought in ethicists to consult on the system, did not want to put a finger on the scale in any way, he said. Instead, selections would be random.

“It’s the only fair way to allocate,” the official, Dave Lennon, said, even as he acknowledged, “it’s not an ideal situation.”

“The alternative is not do anything, which we didn’t feel like was a good option,” he added.

He said if the supply was sufficient, Novartis hoped to expand the program.

Novartis would not say how many people were being selected each time. Drawings are set to take place every two weeks.

And that means families in desperate need have a chance to obtain the medicine just as often.

“For them, they try every possible way to get this Zolgensma,” said Csilla Galik, a friend of the family of Noel Ölyüs, who has type 1 SMA and whose family lives in Romania near the Hungarian border. “They need to try every possibility because this medicine’s price is incredible.”

Beyond Zolgensma, there is another treatment for SMA: Spinraza, manufactured by the drug maker Biogen and more widely available globally. Injected into the spinal fluid every few weeks and then every four months, it promotes the production of the SMN protein by boosting the activity of another gene similar to SMN1.

Many of the children waiting for Zolgensma are already receiving Spinraza, and their parents say it appears to be helping, to an extent.

Wynter Clarkson’s motor function has improved, though not as much as her parents had hoped it would. She can move her head and raise her arms, and can sit up with a back brace. She can rock from side to side, but not quite roll over. Each treatment requires the family to travel about two and a half hours from their home in Toowoomba to Brisbane.

Spinraza and Zolgensma have not been compared in a head-to-head study, and how long the benefits of Zolgensma last is not yet known. But parents said they see a one-time infusion of Zolgensma — which replaces the faulty gene at the root of the disease, instead of just building a workaround — as the best option for their children.

Even when children are on Spinraza, their disease can progress, if at a slower rate, parents said.

Blair said her daughter, Lennon, has more control over her head and limbs since starting Spinraza. But after three doses, the girl still needed a feeding tube inserted; she lost her ability to swallow. That’s on top of other care required by Blair and other parents of infants with the disease. Oxygen levels needed to be checked, sleeping sometimes requires a mask and machines to aid breathing, physical therapy exercises are done to try to coax some muscle activity.

“You basically repeat that all day, all day until bed time,” said Blair, of St. Catharines, Ontario. “And everything takes so long.”

There is another wrinkle to having a child with the disease: It’s inherited, and some parents — though not all — said they felt responsible for having passed on a mutation that made their child so sick.

To have the disease, a child needs to inherit two mutated copies of the gene, one from each parent — who can go through life not knowing they are carrying the mutation until they have a child with the disease.

The parents who have struggled with a sense of guilt know they shouldn’t blame themselves, but they still catch themselves wondering if there was something they could have done differently.

“It’s something we technically gave to her, not even knowing that we could,” said Laura Silva, the mother who lives near Toronto. “And that’s the hardest part.”

When it came time for the lottery drawing this week, her daughter Rebecca’s name wasn’t in the pool — she hadn’t yet gotten the necessary approval from a Candian health authority to try an experimental drug. It’s not clear how many Canadian children found themselves in similar circumstances, or how many were successfully entered by their doctors. Some parents said they were still waiting for that approval.

Noel, the boy in Romania, was entered by his doctor. But his family had not heard anything following the initial drawing. Neither had the Clarksons in Australia:

“No word from our neurologist about the free Zolgensma dose,” Jamie wrote in an email Tuesday, “so I’m assuming Wynter wasn’t picked this time around, unfortunately.”

Winnie Luk-Taylor with daughter Skye. Winnie Luk-Taylor

Winnie Luk-Taylor and Cory Taylor, who live outside Toronto, were once hopeful that Zolgensma could help their daughter, Skye.

She was born in June. Her motor skills weren’t developing as they should have, and her breath had a rattle to it, as if she were congested. At around 4 months, Skye was diagnosed with SMA and, with a cough, her parents were told to take her to the hospital. She was also started on Spinraza.

She spent a month and a half at the hospital with respiratory infections and complications. She died Dec. 21.

“Skye took it all in and smiled at every one and didn’t seem to realize she was experiencing some very, I guess, major medical procedures,” her mom said. “She was a very good-natured girl.”

Luk-Taylor said she sometimes wondered what might have happened if Skye had been born one year later — June 24, 2020, not 2019. Ontario, the province where they live, started testing for SMA this year as part of its newborn screening, meaning Skye might have been diagnosed earlier in her life and started on Spinraza sooner. Maybe it could have had more of an effect. And maybe Zolgensma would have become available to Canadian babies not long after that.

Instead, at Christmas, Luk-Taylor wrote her daughter a poem.

“We will never let you go,” it reads in part.

“Your spirit will live on

It lives in everything I do

I will always fight for you

I will always care for you

I will always dream of you

I got to see who you were to become

And I am blessed and proud of you

I am blessed and proud of you

I hope you see and hear me now

And know that I love you.”