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The world’s most expensive medicine could save toddlers’ lives. But getting it is complicated

Estelle Lemieux, a 21-month-old with spinal muscular atrophy, practiced using her new wheelchair outside of her home in Walpole. Estelle will be getting a treatment of Zolgensma after her insurer, Aetna, decided to cover the $2.1 million drug.
Estelle Lemieux, a 21-month-old with spinal muscular atrophy, practiced using her new wheelchair outside of her home in Walpole. Estelle will be getting a treatment of Zolgensma after her insurer, Aetna, decided to cover the $2.1 million drug. (Jessica Rinaldi/Globe Staff)

Who deserves to get a potentially life-saving treatment? How severe does the disease have to be? At what age should someone become ineligible?

These questions are tormenting families trying to obtain Zolgensma, the world’s most expensive drug. The $2.1 million gene therapy was approved in May for children up to the age of 2 with spinal muscular atrophy, a rare disease that kills more infants than any other inherited disorder.

A 21-month-old girl in Walpole is scheduled to receive the breathtakingly expensive medicine soon, after her health insurer recently reversed its initial denial of coverage.

But a 2½-year-old girl in Easton with a worse form of the disease was recently deemed ineligible to get Zolgensma through a special program set up by the company that sells it. Her family and physician had argued that she met the criteria for the compassionate use program, which was set up before the drug won approval, but the company disagreed.

Marisa Boidi kissed her daughter, Natalia, in Natalia's room at their home in North Easton.
Marisa Boidi kissed her daughter, Natalia, in Natalia's room at their home in North Easton.(Nic Antaya for The Boston Globe)

“Welcome to the world of rare-disease medicine,” said Dr. Kathryn Swoboda, a neurologist at Massachusetts General Hospital, who treats both girls and participated in the clinical trials of Zolgensma. “I feel so bad for these families.”

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The contrasting fortunes of Estelle Lemieux and Natalia Boidi illustrate how Zolgensma’s approval has led to an emotional roller coaster for some families of children with spinal muscular atrophy, also called SMA. Afflicting one in every 6,000 to 10,000 babies, the disorder attacks the neurons that control muscle function. Its most dire form kills most children by their second birthday.

Many people were elated when the Food and Drug Administration approved the gene therapy on May 24 to treat all forms of the disease in children up to that age. Marketed by Illinois-based AveXis, a subsidiary of the Swiss drug giant Novartis, Zolgensma replaces a defective gene responsible for making a protein for muscle control with a working one. In clinical trials, a one-time intravenous treatment helped infants and young children breathe on their own and achieve motor milestones, like sitting up without support.

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Novartis is one of the biggest pharmaceutical employers in Massachusetts, with more than 2,300 workers and a sprawling biomedical research complex in Cambridge.

Zolgensma’s price tag isn’t the only aspect of the treatment that has stirred controversy. On Tuesday, the FDA said AveXis delayed disclosing that one or more people at the subsidiary manipulated animal testing data for the medicine, although the agency says the drug should stay on the market.

AveXis won’t disclose how many children in the United States have received Zolgensma since FDA approval, but the company says it has been dispensed to a “wide range of patients with different SMA types.”

Mass. General and Boston Children’s Hospital participated in clinical trials and are starting to provide commercial doses of the drug.

Among those who desperately want it is the family of Estelle Lemieux, a Walpole girl who uses a wheelchair. Estelle’s mother, Amy Lemieux, noticed something amiss with her daughter about six months after her birth in Florida. She struggled to lift her head, and her body seemed floppy.

Estelle Lemieux sat with her mom, Amy, as they posed for a portrait at their home.
Estelle Lemieux sat with her mom, Amy, as they posed for a portrait at their home.(Jessica Rinaldi/Globe Staff)

Lemieux at first thought Estelle might be developing slowly because of upheaval in the family’s life. The house where Amy Lemieux and her husband, Douglas, lived in Bradenton, Fla., was destroyed by Hurricane Irma in September 2017, shortly before Estelle’s birth. In the months afterward, the family had to relocate several times before moving in with Amy’s parents in Massachusetts.

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When Estelle remained weak, her parents took her to Mass. General. In February, at 16 months old, a blood test determined Estelle had Type 2 spinal muscular atrophy.

While not the most serious form of the disease — Type 1 has invariably been a death sentence — the disease has kept her from reaching many motor milestones, including sitting up by herself, lifting her head while lying on her abdomen, and crawling.

Swoboda recommended a breakthrough drug called Spinraza, sold by Cambridge-based Biogen. Approved in 2016, Spinraza was the first treatment for spinal muscular atrophy. It’s injected into the spinal canal and helps make more of the protein that controls muscle movement.

Spinraza, too, carries a steep price tag: $125,000 for each 5-milliliter dose. Patients need six doses the first year, at a cost of $750,000, and three doses every year afterward, at an annual expense of $375,000.

After receiving four doses at Mass. General, Estelle seems a little stronger, her mother said. But when the FDA approved Zolgensma, Amy Lemieux contacted Swoboda and applied to the family’s health insurer, Aetna, to cover the newer drug, as it had with Spinraza.

While more expensive, Zolgensma also seemed more cost-effective than Spinraza, since it is a one-time treatment. Proponents say the drug might even be better because it replaces the defective gene with a functioning version, rather than strengthening a backup gene, as Spinraza does.

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“Spinraza is like giving your daughter dialysis, whereas the gene therapy is like replacing the organ she’s missing,” Amy Lemieux said.

But in late July, Aetna rejected the application for Estelle. The insurer said the child failed to meet criteria to qualify for coverage, including that she have the worst form of the disease, even though the FDA approved the drug for all types of SMA in children up to 2 years old.

Amy Lemieux was crestfallen. She was particularly upset because her husband has worked more than five years managing stores for CVS Health, which recently acquired Aetna in a $69 billion deal. But three days later, she got a call from a physician who works for Aetna. The insurer had reversed itself.

“I started bawling on the phone,” Lemieux recalled. “I felt like I won the lottery.”

A CVS Health spokesman said clinical data on Zolgensma were limited, but “the promise of the medication led us to reconsider our approach” and broaden coverage.

Lemieux expects her daughter will get Zolgensma within days and no longer be eligible for Spinraza.

Like the Lemieux family, Marisa Boidi, who works for a direct marketing firm and lives in Easton, was thrilled when she heard about clinical trials of the gene therapy. Her daughter, Natalia, was diagnosed with the worst form of the disorder as an infant and has multiple health problems.

Natalia Boidi watched television at her home.
Natalia Boidi watched television at her home.((Nic Antaya for The Boston Globe)

She can’t swallow liquids, has a feeding tube inserted into her abdomen, uses a breathing machine at night, and often needs her parents to clear mucus from her airways with a suction device. On a recent weekday, she cheerfully watched TV on the sofa with an oxygen monitor tethered to the big toe on her right foot.

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Natalia began gasping for air when she was about five weeks old in 2017 and had a breathing tube temporarily inserted into her throat. She was diagnosed with Type 1 spinal muscular atrophy and spent more than two months in the pediatric intensive care unit at Mass. General.

At Swoboda’s recommendation, Natalia began receiving infusions of Spinraza. She’s had 10 so far. Marisa Boidi said the drug saved her daughter’s life and has enabled her to sit, with some support. Indeed, Boidi is so enthusiastic about Spinraza that she speaks to other families about it occasionally and gets paid by Biogen to spread the word.

Nonetheless, in the spring she asked Swoboda about applying for Zolgensma through a compassionate use program run by AveXis. Drug companies sometimes set up such programs for patients who aren’t in clinical trials but might benefit from free experimental medicines.

Natalia was already 2 years old, but AveXis did not set an age limit for compassionate use for Type 1 patients with symptoms. Children needed to weigh less than 29 pounds — Natalia weighs 26 pounds — and satisfy other criteria, all of which she met, according to Swoboda.

With guidance from AveXis, Swoboda ordered several tests for Natalia in preparation for the dosing. On July 23, Swoboda e-mailed the Boidi family with bad news. AveXis, Swoboda wrote, “reversed their decision” on several patients of hers whom it had initially approved for Zolgensma, including Natalia.

Marisa Boidi (left) and Kate Long of Carver watched as Natalia rolled around in her wheelchair.
Marisa Boidi (left) and Kate Long of Carver watched as Natalia rolled around in her wheelchair.(Nic Antaya for The Boston Globe)

“I’m devastated,” Marisa Boidi told the Globe. “I don’t understand exactly what happened, other than the fact that I thought my daughter was being entered into this managed access program and then all of a sudden she wasn’t.”

An AveXis spokeswoman said Tuesday that Natalia has been in line to receive Zolgensma but was rejected because the firm concluded she has the Type 2 form of the disease, not the worst kind.

But Swoboda said the only reason Natalia appears to have the less serious form is because she has improved as a result of Spinraza.

“That makes no sense,” the neurologist said.

Three of Swoboda’s other patients did obtain Zolgensma through the compassionate use program, according to AveXis.

All told, Swoboda has provided Zolgensma to 10 children during the clinical trial and through the compassionate use program. Estelle Lemieux will be her first patient to receive the medicine since AveXis began selling it.


Jonathan Saltzman can be reached at jsaltzman@globe.com.