Stories of Lives Transformed: A Chance to Walk and Breathe
Whenever I talk about our work, much of the attention goes to the remarkable, accelerating science behind cell and gene therapies and the extraordinary costs. Yet every one of these amazing treatments represents a defining moment in the lives of a patient and their family. The impacts are so personal and dramatic, you could make a movie for each story, capturing the trajectory of lives that take a terrible turn into fear, struggle, and despair – only to be saved by an astounding scientific breakthrough that seems part science fiction and part miracle in its power to cure or reverse a terrible disease or condition.
As we strive to create a better system for delivering these transformative therapies in an affordable and sustainable way, I find inspiration in the lives of patients and their families who show amazing courage and resilience in confronting their worst fears and finding hope and new life in science and medicine.
Imagine the fear of a parent who has lost a child to a terrible disease and then learns that their newborn baby has the same genetic mutation. That’s what happened to Milan and Elena Villareal. Their first daughter, Josephine, was six months old when she was diagnosed with Spinal Muscular Atrophy (SMA) Type 1, a genetic condition affecting 1 in 10,000 babies that causes muscle wasting, paralysis, and early death. They were helpless over the next excruciating year as the disease took its course and Josephine passed away at just 15 months of age.
When Elena became pregnant unexpectedly, they knew that their baby would have a one in four chance of developing the same condition. They lived with that fear through the pregnancy until Evelyn was born in December, 2014. When the doctors tested her for SMA, the nightmare became real.
That night, Milan turned in desperation to the internet, searching for news of any kind of medical breakthrough or hopeful treatment. He came across a clinical trial at Nationwide Children’s Hospital in Ohio for a new cell and gene therapy that was open to children under 6 months diagnosed with SMA Type 1. Few children are tested until symptoms have escalated, as was the case with Josephine, so six months is a difficult timeline. In that sense, Evelyn was lucky. At eight weeks of age, she was enrolled with 15 other babies for the new treatment now known as Zolgensma.
Zolgensma comes in a single intravenous infusion that takes 60 minutes. It works by using a virus to deliver a functional copy of the SMN1 gene directly to the patient’s motor neuron cells. This gene immediately starts instructing the cells to produce a protein needed for muscle control and movement. Since nerve cells don’t divide, the gene stays active long-term.
The clinical trial was an unequivocal success. All 15 babies who received the new treatment lived. Zolgensma does not reverse the nerve damage that has already taken place but it stops the disease from progressing. Evelyn’s treatment started early enough that she was able to avoid much of the potential damage. She developed strength in her muscles and learned to walk. Today, Evelyn is 11 and goes to school like any other healthy child. “I forget that she has SMA,” Elena says. “She’s a healthy girl and does everything a normal child would do.”
Zolgensma was approved by the FDA in 2019. To date, around 4,000 children have received the drug – and the success rate is almost unimaginable. SMA kills 90% of children by age 2 but those treated with Zolgensma have achieved a 97.5% long-term survival rate.
For children, like Evelyn, who are treated before symptoms appear, 96% learn to walk on their own and 100% are able to live without permanent breathing support. Patients treated after symptoms appear may not be able to walk or sit up on their own or avoid feeding tubes. But they live years longer than untreated patients.
Cost is one of the biggest barriers to access. At one point, Zolgensma was the most expensive drug ever at $2.1 million for a single dose. Many families have struggled to get authorization or treatment coverage for their children.
Lucy Van Doormal, for example, was born in Vancouver, Canada, in 2020. Her parents, Laura and Scott, were overjoyed to bring home a new baby but a few weeks later, she was unable to lift her hand to her mouth to suck her thumb and seemed to be struggling to breathe. Frightened, they brought her to the doctors who tested her and confirmed a diagnosis of SMA.
Like Evelyn’s parents, Lucy’s parents frantically searched for help and learned about Zolgensma. Lucy was a perfect candidate but their hope turned quickly to dismay. Zolgensma had not yet been approved in Canada and wasn’t covered by insurance.
Fighting for treatment coverage while caring for Lucy was traumatic enough, but it soon became clear that the Van Doormals would need to somehow raise the money to pay for the treatment themselves. They launched a Go Fund Me campaign and did everything possible to draw attention to Lucy’s needs. Amazingly, they managed to raise $2 million, but it was still not enough to cover treatment costs. Then they learned about a program launched by Novartis, the drug’s manufacturer, to provide Zolgensma at no cost to 100 patients under the age of 2 in countries that hadn’t yet approved the drug. Lucy was one of the lucky children chosen in that lottery for life.
The delay in receiving treatment, however, meant that Lucy’s symptoms had already progressed significantly. But the drug had an immediate impact. According to Lucy’s mother, “The biggest changes are her head control. Really quickly after the treatment she was able to hold her head up, which is something she’s never done before. She can sit with some support and hopefully one day she’ll crawl. Maybe one day she’ll even walk.”
Even in the U.S. where Zolgensma has been approved, parents often need to fight for coverage even as health plans fight to control costs. We need to make sure this isn’t a reality for parents and patients in the future.
A recent 60 Minutes episode brought that struggle to light with the story of Maisie Green, born in Colorado in 2017. Maisie’s mother, Ciji, was alarmed when her baby seemed to be losing physical strength rather than developing it. Genetic testing soon gave them the dreaded SMA Type 1 diagnosis.
A few months after the diagnosis, the FDA approved Zolgensma, but the drug had a $2.1 million price tag. When the Greens’ health plan denied coverage, they said it was because Maisie was almost six months old, nearly past the optimal age timeline for treatment.
Ciji Green was outraged. "I became very angry to know that there was something that could help her. And I knew without a shadow of a doubt I was burying my daughter before she was 2."
She went into action, raising money for treatment, interviewing with local news outlets, and launching a grassroots advocacy group that attracted 700 volunteers and called itself “Maisie’s Army.” Their social media campaign to convince the health plan to overturn its decision went viral, and Ciji was able to get an in-person meeting with insurance company representatives.
Under pressure, the insurance appeals board reversed the denial and agreed to pay. Maisie finally received her infusion in 2019, halting progression of the disease. Though unable to walk, Maisie is alive, attending school, and getting straight A’s. And Maisie’s Army has continued to advocate for SMA patients, helping to overturn denials for more than 16 other children.
It shouldn’t be this hard for patients and families to get timely access to breakthrough, life-saving treatments. Cost is a formidable barrier with CGTs but not an insurmountable one if we pool resources among payers, work with drug manufacturers on pricing and effectiveness guarantees, and support health systems in developing the necessary treatment infrastructure.
That sounds like a lot, but it’s nothing compared to the benefits of building a system that makes such breakthroughs sustainable and saves precious lives. That sense of purpose and the potential for a much better future guides us at Aradigm.
