‘It’s a real-life Hunger Games’: a lifesaving drug costs $2m, but not every child can get it

Elizabeth Wraige remembers the first time she delivered the diagnosis. “Parents feel as if they’ve been hit by a sledgehammer,” she says. Her patient, a baby boy, had been born tiny and perfect to overjoyed parents six months earlier. But they had begun to feel something was not right. He seemed floppy and was not moving normally. Tests showed he had spinal muscular atrophy (SMA), the most deadly genetic condition in children under two, in which a deficit of a crucial protein causes motor neurons to die, and the body slowly loses the ability to move. Babies with untreated type 1 SMA, the most severe form, will never sit, crawl or speak and are slowly robbed of the ability to move, swallow and breathe. Most die before they are two.

“In that conversation, any hope that it was something that could be remedied was taken away,” says Wraige, a paediatric neurologist at Evelina London children’s hospital. “It was devastation.” She could offer only one shred of consolation: SMA, an incurable condition that affects one in 6,000-10,000 children, is at least not painful.

That was more than a decade ago. Recently the prospects for children diagnosed with SMA have improved dramatically, thanks to three groundbreaking drugs. The world’s first SMA drug was Spinraza, approved in the US in 2016. Another, Risdiplam, marketed as Evrysdi, has only recently become available in the UK. But it is Zolgensma, a drug made by the pharmaceutical company Novartis, that offers the most tantalising hope. While the other two treatments involve taking daily oral medication or undergoing a lumbar puncture four times a year for life, Zolgensma is administered via a single, hour-long intravenous infusion that has the potential to stop the degeneration caused by SMA in its tracks.

If given at birth, before symptoms develop, doctors believe that the one-shot treatment could approach a cure. But the older the baby, the less effective and riskier the treatment, leaving families in a desperate race against time. And there’s another hurdle: it costs $2.1m (£1.6m) a dose. When it was licensed in the US in 2019, this made it the most expensive drug in the world.

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The cause of SMA has been known since the 1990s. Babies with the condition are born with a faulty version of a gene called SMN1, which leaves the body unable to make enough of a protein that motor neurons – which control muscle movement – need to survive. When the body starts running a deficit, motor neurons die, the body loses the ability to move and paralysis sets in. (Types 2, 3 and 4 SMA are less severe versions of the disease.)

SMN1 was discovered at a time when the promise of an entirely new form of medicine – gene therapy – was coming into focus. The vision was that diseases caused by a faulty gene could be treated by delivering a working version of the gene directly into cells. The relevance for SMA was obvious. But turning it into a treatment proved to be elusive.

To treat SMA, you have to find a way to reach the motor neurons in the spinal cord – but they sit beyond the blood-brain barrier, a largely impermeable membrane that shields the brain and central nervous system. Then in 2005, Martine Barkats, working at the French biomedical charity Généthon, discovered a harmless virus that had a unique ability to cross the barrier. She tested it in mice that were genetically engineered to have the defect that causes SMA – and struck gold.

“The effect on the survival times of the mice was dramatic – really amazing,” says Barkats, now at the Institut de Myologie in Paris. “We knew that it could be a very important treatment for SMA patients.”

A pair of US scientists who had been working on a similar concept agreed. By 2012, they had founded a startup, AveXis, and two years later launched the first patient trial of their drug. Word of the trial spread rapidly, with parents sharing scientific papers on Facebook pages.

• Arnaud Robert and Paolo Woods write: Zach, who lives in the suburbs of Chicago, was born with SMA, and given Zolgensma in October 2019, when he was eight months old. His father’s trucking union funded the millions needed. Zach also takes a daily medication.

• ‘Two weeks after Zach was born, I felt something was off,’ his mother says. ‘He threw up all the time.’ Medical institutions were not helpful, but when she posted videos of Zach on a local school’s Facebook page, ‘I was flooded with messages from mothers who realised he had SMA. It was really scary because the first thing Google tells you is it’s the number one killer of infants. I closed my laptop, went to the neurologist and requested a test.’ Zach was diagnosed at seven months.

• The family live in one of the 40 countries where Zolgensma is reimbursed by insurance companies or covered by public healthcare. If they didn’t, Zach might be the subject of one of the many social media campaigns started by families desperately crowdfunding. Some fundraising companies, such as Impact Guru in India, even orchestrate such campaigns for a share of the money raised.

Louis, from Sydney, was the 11th baby in the world to be dosed with Zolgensma in October 2015. His parents were alerted to his condition unusually early because Louis is a twin. When the one-month-old babies were laid face down, Mila, Louis’ twin, would raise her head and look around, but Louis would just lie there, barely moving.

“I said to my GP: ‘I know you’ll think I’m crazy – he’s a newborn and newborns don’t move a lot but there is something wrong,” recalls Maria, Louis’ mother.

The doctor agreed and sent Louis for tests. He was diagnosed early, before he was two months old, and within days his parents had secured a place for him on AveXis’s trial at a children’s hospital in Ohio. “I remember the day of his treatment as a second chance in life,” Maria says.

The trial results were striking. Ten of the 21 babies, all treated before six months, could sit up by about 12 months. Some went on to crawl, stand and walk. (The impact on life expectancy isn’t yet known, but doctors expect some will live independently as adults.)

AveXis licensed the patent on Barkat’s discovery and the company was bought by pharmaceutical multinational Novartis for $8.7bn in 2018. The FDA approved Zolgensma in the US the next year, with a European licence following in 2020.

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Journalist Arnaud Robert and photographer Paolo Woods have been meeting and documenting the families of the first babies to receive Zolgensma as part of Happy Pills, a long-running project on the role of medicines in the modern world. The drug’s $2.1m price tag, they say, gives it a “miracle drug” cachet and taps into parents’ desire to “make my child normal”. But the stark reality is many countries can’t afford to provide it, leaving parents to turn to crowdfunding. Social media is filled with emotional posts making desperate requests for donations.

The price has drawn criticism, with a group of five US senators, including Bernie Sanders and Elizabeth Warren, accusing AveXis of “privilege and greed”. Barkats, the French scientist, shares this concern. “I’m really disappointed by this decision of Novartis to sell the treatment at such an expensive price,” she says. “It’s such a devastating disease. It’s putting commercial interests before the lives of children.”

People say Zolgensma is so expensive. But if you look at other drugs over a lifetime, you’ll see those cost much more

“We have to look at the cost over a lifetime,” says Mike Fraser, a general manager at Novartis Gene Therapies. “People say a product like Zolgensma is so expensive. But if you look at other drugs, such as in oncology, over a lifetime, you’ll see that those are much more expensive. We do believe that it’s a very fair and value-based price.” (Spinraza, the SMA treatment from rival pharmaceutical giant Biogen, which is taken every four months, costs $625,000 to $750,000 in the first year, and then about $375,000 every year afterwards.)

Francesco Muntoni, a paediatric neurologist at Great Ormond Street hospital in London, says the success of Zolgensma, Spinraza and Risdiplam, the oral medication licensed last year, took the entire field by surprise. The outcomes for his patients are “unrecognisable” in comparison with only a few years earlier.

• It took months of negotiations with the pharmaceutical giant to gain access to the only place where Zolgensma is produced, the Novartis Gene Therapies plant in Libertyville, Chicago – an anonymous hangar in the suburbs. Once finally inside, we were suddenly told we would not be allowed to take photos as they were getting ready for a visit from the FDA. A few calls – and hours – later, we were authorised to take just a few photos in limited areas. The technicians work in a sanitised and isolated environment – we were allowed to photograph it only through a window.

• ‘When I go to work, I tell my children that I am going to save babies and they are proud of me,’ one employee told us. The office walls are lined with TV screens that loop testimonials of families thanking Novartis for their treatment. Each hand sticker represents a baby injected with Zolgensma – over 1,400 so far – and is marked with their name, country of origin and injection date.
  

• Though it was hard to forget that we were in the plant that produces one of the most expensive drugs in the world, it felt as if we were in a startup. There were still signs up that read “AveXis” (the name of the startup that developed Zolgensma, which Novartis bought). The fact that gene therapies are tailored for patients, and that Zolgensma is one of the first medicines on the market to use such techniques, makes the entire operation feel more like an experimental lab than an industrial enterprise.

“In neurology, they are among the most effective drugs produced in the last few decades,” he says. Referring to a child he treated who had pre-symptomatic SMA and is now three, he says, “I cannot tell if she had SMA or not.” The girl’s older sister, by contrast, uses a wheelchair, will never stand or walk, and depends on a ventilator to breathe.

“Essentially, every child is surviving now,” Muntoni adds. But he is wary of giving false hope and says that hype around Zolgensma has left some parents with unrealistic expectations.

Its single treatment is the preferred option for most babies who are diagnosed very early. But as infants grow, an exponentially higher dose is required, which comes with a risk of complications and diminishing benefits.

“One also still has to distinguish between miracles and effective drugs,” Muntoni says. “When the condition has advanced beyond repair, no drug will reverse that.”

Robert and Woods recently spoke with Louis, who is now six and back in Sydney. “On one hand, the results are amazing. This kid would have died,” Robert says. “But Louis is in a wheelchair, he’s been to ICU seven times, he has someone sleeping in his room every night because they are scared about respiratory issues. Zolgensma is not a miracle drug.”

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In the UK, the NHS struck a deal with Novartis last year that secured the drug at “a substantial confidential discount”. The NHS has to ensure that a drug is cost-effective, but the finer details of how these deals are struck are shrouded in secrecy, with a clause stating that the final price remains confidential “in perpetuity”. Zolgensma is automatically available in this country for babies under six months with type 1 SMA – but the more finely balanced risk-benefit ratio for older babies means that doctors consider these on a case-by-case basis.

• Zion, three, has physiotherapy sessions at the Lurie children’s hospital in Chicago. The floor is covered with small cars. For exercise, he rolls the cars on the bed until they fall off; each time he succeeds, his mother and the physiotherapist let out great sighs of relief. Sometimes he grows tired of having to stretch his chest, push with his arms and raise his head, so he covers his ears in an almost theatrical way, to say he has had enough.

• One Sunday, we joined Zion (pictured with his brothers) and his family at the megachurch in Chicago where his father is an evangelical pastor. His parents gave him his name – meaning heaven, the promised land – long before they learned he had SMA. Now, ‘I find that resonates even more. He is our blessing,’ his mother, Bethany, says.

• Zion plays with his sister and father. His parents hope Zion can access Spinraza injections in addition to Zolgensma, but the insurance companies are reluctant.

Timing of the treatment is critical: about 70 babies are born with SMA in the UK each year, but the average age of diagnosis is five months, which many consider too late. “If you intervene on the day they become symptomatic, about 80% will sit, a few will stand or even walk,” Muntoni says. “By five months, a minority will be sitting and none will be standing or walking.”

The disease is rare enough that many GPs will not have encountered it, and the earliest symptoms are similar to those of other conditions such as muscular dystrophy or cerebral palsy. Some parents do not realise something is wrong. Others are dismissed as overanxious and spend weeks or months in diagnostic limbo.

Muntoni’s frustration at this is palpable. Since treatments became available, most US states have added SMA to the conditions screened for at birth and six European countries have approved SMA screening. The UK has ambitious plans to expand newborn screening, but this overhaul could take at least five years. A campaign has been building, led by SMA UK and doctors, including Muntoni, to make a change far sooner. “If we wait five years, there will be more than 350 children who could have been saved,” he says. “As doctors, we do what we can. We tackle fires, but it’s better for the fires not to happen.”

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How many buyers are paying Zolgensma’s $2.1m price tag? The opacity of negotiations between pharmaceutical companies and healthcare providers means that different countries are paying different amounts for the drug. But most government buyers will secure significant discounts. By contrast, poor families in India who are crowdfunding their treatment pay the list price, Robert says. Some travel thousands of miles to be treated.

To address global access, since 2020 Novartis has committed to offer free treatment to 100 babies each year in countries where Zolgensma has not received regulatory approval, via a lottery-style draw – one where the stakes are unbearably high. The initiative, in which babies are selected randomly by a third party, has had a mixed reaction. The campaigning group Just Treatment likened the draw to a “real life Hunger Games”, while the charity SMA Europe expressed alarm at the prospect of babies competing for a lifesaving treatment.

If you can’t treat babies fairly, do you do nothing? The inequities are part of a wider societal and political issue

Wraige says, as a doctor, she finds it hard to reconcile living in a world where some babies can be treated and others cannot. But she adds: “If you can’t do it fairly, do you do nothing? I don’t think that either. The inequities are part of a wider societal and political issue.”

Novartis’s Fraser says that, after consulting independent bioethicists, the programme was judged to be the “fairest way” to allocate free doses, which to date make up about a tenth of the 1,800 treatments that have been given globally. “The principle of fairness is one we took seriously,” he says. “We’d love to give it to everyone, but we can’t do that.”

Did the company consider making the drug more affordable? “One could ask that question for anything in the world – why not make it cheaper?” Fraser says.

This pragmatic appraisal of global health inequalities contrasts with Fraser’s idealistic hope for the future of Zolgensma. “I have a vision,” he says. “One day, you’ll be able to look out at a playground of children and you wouldn’t be able to tell who had SMA or not.”

Zolgensma was recently displaced as the “world’s most expensive” by another drug, Libmeldy, for another rare genetic disorder, which the NHS has also agreed to fund. But expensive drugs don’t tend to stay quite so expensive for ever – as competition arrives in the market there will be pressure to lower prices. And health systems adapt to new realities. Now that there are treatments, early diagnosis has become an urgent priority.

“Without treatments, there was no hope,” Barkats says. “Now, there are four-year-olds who are living, eating, speaking and sometimes walking.” Wraige, who used to break the devastating news to parents more than a decade ago, says the conversation today is entirely different: “The starting point is still that you have this devastating diagnosis,” she says. “But we then move on to the available treatments. Whether it costs 5p or over £1m doesn’t come into my mind.”