Strimvelis, the gene therapy rejected by the pharmaceutical industry that has saved Aitana

In March 2021, as the world began emerging from the pandemic thanks to Covid-19 vaccines, Mari Carmen Gómez locked herself and her newborn daughter in an isolation room at the Reina Sofía Hospital in the Spanish city of Córdoba. “We spent six months inside those four walls. Aitana was a baby with tubes, so I couldn’t do much with her, but I was in anguish. Netflix and my phone saved me,” jokes Gómez, a 30-year-old olive harvester from Santaella, 30 miles from Córdoba.

Aitana, born two months earlier, had been diagnosed with severe combined immunodeficiency of adenosine deaminase (ADA-SCID), a rare genetic disease — occurring in just one newborn per year in Spain — that destroys the immune system’s cells. It is one of the most severe forms of what is colloquially known as “bubble baby syndrome,” where patients are forced to live in complete isolation because even a minor infection could be fatal.

Today, Aitana is a lively, happy, and curious child who is about to complete the first term of her first year at nursery school. Her immune system is fully functional, thanks to gene therapy — an innovative treatment in which a virus, in this case a retrovirus, is modified to deliver a healthy gene into the patient’s body, acting like a Trojan horse to replace the defective gene.

But while gene therapy saved Aitana’s life, the treatment that cured her, Strimvelis, faced its own life-or-death challenge. Strimvelis was nearly discontinued due to poor commercial prospects, as two pharmaceutical companies — GSK and Orchard Therapeutics — abandoned its production. Its survival is thanks to the Telethon Foundation, affiliated with the San Raffaele public hospital in Milan, Italy, which has pledged to continue producing the treatment on a non-profit basis.

“It was hardly acceptable for the medical-scientific community that a gene therapy that has been shown to provide long-term benefit for patients should no longer be available,” the foundation’s officials explained in a written response to EL PAÍS.

César Hernández, Director General of the Joint Services and Pharmacy Portfolio at Spain’s Ministry of Health, called the outcome “very heartwarming,” noting that the research leading to Strimvelis began at San Raffaele Hospital over two decades ago. The therapy has come full circle, “returning to the very public institution where it was born,” he said.

The disease Aitana overcame is described by Manuel Santamaría, a professor of Clinical Immunology and her specialist, as a kind of “recycling failure” in the body’s genetic material. “Immune system cells need to replicate millions of times very quickly to deal with viruses and bacteria. To do this efficiently, the body reuses components of genetic material from other cells that have already been damaged,” he says.

In ADA-SCID patients, this process is disrupted by the absence of an enzyme. “Without it,” Santamaría continues, “the body cannot complete the cycle, and toxic metabolites accumulate in immune system cells. Because they are toxic, these cells end up destroying T lymphocytes, B lymphocytes, and NK cells” — an acronym for Natural Killers, so named for their role in eliminating pathogens.

Studies suggest that one in every 50,000 children is born with a genetic disorder under the umbrella of bubble baby syndrome. “There are roughly 500 primary genetic immunodeficiencies. ADA-SCID accounts for about 15% of these cases, so we estimate it affects roughly one in every 400,000 live births,” explains Pere Soler, head of the Pediatric Patient Infections Group at Vall d’Hebron Hospital in Barcelona.

A stem cell transplant from a family donor is typically the first curative option for ADA-SCID patients. Unfortunately, for Aitana, none of the nearly 50 potential donors screened were compatible. “If this fails, a bone marrow donor can be sought outside the family, but this is a complex process with a risk of serious complications and a failure rate of about 15%,” says Soler.

In Aitana’s case, this first option failed. “We consulted the Josep Carreras Foundation donor bank, but there was no compatible donor,” Santamaría recalls. “Everything we tried failed. In the end, gene therapy was the only curative option.”

The origins of Strimvelis, the gene therapy that saved Aitana, trace back to the early 2000s. In 2010, Milan’s San Raffaele Hospital partnered with pharmaceutical giant GSK to develop the treatment. This collaboration culminated in 2016 when the European Medicines Agency (EMA) approved the therapy. Despite this milestone, the British pharmaceutical company decided less than two years later to abandon Strimvelis due to poor sales. GSK justified the move as part of a “strategic review” of its “rare diseases unit.”

Orchard Therapeutics, which had other gene therapies in development, acquired Strimvelis in 2018 but halted its investment in the treatment four years later. Facing the imminent disappearance of the therapy, Telethon Foundation stepped in and, as of September 2023, became the owner of the life-saving cure for bubble babies.

This case exemplifies the “tension between innovation and financing,” says Vicente Ortún, a Health Economics specialist and professor at Pompeu Fabra University (UPF) in Barcelona. He explains: “Specific difficulties arise with rare diseases, since they tend to have a high cost, as companies hope to recover the costs of innovation in the face of limited demand. What’s more, these are companies that seek to achieve high profits, since the pharmaceutical industry continues to be the most profitable.”

In 2016, GSK priced Strimvelis at €594,000 ($623,000), making it one of the world’s most expensive treatments at the time. However, this figure pales in comparison to the more than $3.5 million charged for newly approved gene therapies. The Telethon Foundation has kept Strimvelis at its original price. “We are working hard to ensure the sustainability of Strimvelis production, seeking a balance between costs and income. It’s not an easy task if one takes into account that the small number of patients treated each year limits income, while a large part of the costs are fixed,” explains the foundation.

Since its commercial release in 2017, Strimvelis has been administered to 22 patients — “fewer than four per year,” the Foundation explains — at San Raffaele Hospital in Milan, the only facility authorized to deliver the therapy. Aitana is the first and only patient from Spain, with her treatment covered by the Andalusian regional government. Previously, during its experimental phase, other Spanish children participated in clinical trials.

Experts believe the results of Strimvelis are very good. According to recent data, “77% of treated patients remain disease-free 10 years after receiving therapy and require no additional medication or interventions,” reports the Telethon Foundation. This is the situation Aitana now enjoys.

With Strimvelis’ availability secured, experts are shifting their attention to the issue of delayed diagnoses. “It’s urgent to move forward with the universalization of neonatal screening, the so-called heel prick test, which allows for earlier identification and better care for affected children,” says Raquel Yahyaoui, head of the Clinical Analysis Service at the Regional Hospital in Málaga.

Yahyaoui believes expanding screening is key to ensuring equity within the healthcare system. “Aitana’s story highlights the reach and inclusivity of Spain’s public health system. She wasn’t born in Madrid, Barcelona, or any major European city. She was born in a small town in Córdoba province, and yet this didn’t stop her from accessing a cutting-edge therapy that until recently seemed like science fiction. Advancing neonatal screening ensures all children have the same opportunities.”

This December has been particularly intense for Aitana’s mother, who wakes up early to harvest olives in the frost-covered fields of Córdoba. “Look at how it was this morning, all white,” says Mari Carmen, showing a photo of the frosty olive trees on her phone.

While Aitana’s health has thrived thanks to the healthcare system, Mari Carmen has also used this time to study. “I’ve earned a distance learning degree as a nursing assistant,” she says, almost with the same pride with which she speaks of her daughter. “I want to see Aitana grow up healthy and happy.” Santamaría, now 68 and approaching retirement, sets her another goal: “One day, I want to see you working as a nurse.”

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