Exclusive analysis of biotech, pharma, and the life sciences

F or weeks, Julia Vitarello avoided the room in her home. The fairy curtains she sewed. The sheets. The quiet. But one day, she placed her desk by the window. There, she began spending long hours on a single-minded mission: advancing custom medicines — and sparing others the pain her family has endured.

Four years ago, Vitarello’s daughter, Mila, was given a drug created just for her, the first time a medicine was specifically tailored to one patient’s genetic disease. The drug, called milasen, halted her rapidly progressing condition and later improved her quality of life. But the disease, already in an advanced stage, eventually resumed its assault. Mila died Feb. 11, 2021, at 10 years old.

Now, Vitarello is immersing herself in the business of personalized drugs — both to speed and scale their development — in the hopes of making more rare diseases treatable. It has meant mobilizing an academic consortium that creates custom medicines, and working to tackle policy issues such as drug reimbursement that are critical to the development of so-called “N of 1” therapies.

Your daily guide to what’s happening in biotech.

The need for these medicines, Vitarello and other advocates say, is huge — 3 in 10 children with a rare disease won’t live to their fifth birthday. But so, too, are the barriers. Currently, the development of each individualized drug requires families and researchers to raise upward of $2 million. It also takes a small army of scientists and mountains of paperwork.

Vitarello imagines, one day, drugmakers routinely whipping up custom medicines for newborns with ultra-rare conditions. She strives toward this future from Mila’s old room.

“Creating Mila’s drug was like climbing Everest without oxygen or guides,” said Vitarello, 45. “But we need a clear path and to lower Everest.”

M ila — who was born in Boulder, Colo. — started skiing at 2 years old. Gentle slopes didn’t cut it. “She would point to the top and say, ‘That’s where I want to go,’” Vitarello said. In the summer, Mila raced up wooded hiking trails. All the while, she talked up a storm.

But at age 3, she got stuck on words, and her foot turned inward. At age 5, Mila’s faltering vision meant she was trampling her toys. Neurologists, ophthalmologists, optometrists, and orthopedists — no one could figure out what was wrong.

Finally, doctors diagnosed her with Batten disease. The genetic disorder hampers the body’s process to clear cellular waste, leaving children blind and bedridden before dying at a young age. But doctors could only find one of Mila’s two disease-causing mutations. Finding the second mutation required scouring Mila’s entire genome.

A video plea for help that Vitarello put on social media found its way to Timothy Yu of Boston Children’s Hospital, who specializes in whole-genome sequencing. After a painstaking search, he and his team pinpointed the second mutation that caused Mila’s ultra-rare form of Batten disease. He delivered more relieving news: Mila’s younger brother, Azlan, didn’t inherit the mutations.

Yu had only vowed to find the mutation, but he had another idea. He wanted to engineer a drug with a piece of genetic code to patch Mila’s unique mutation. His inspiration came from programmable drug technology that powers Spinraza, a drug that had recently been approved by the Food and Drug Administration.

A regulatory path didn’t exist for a custom drug. But Mila’s rapidly deteriorating condition convinced the FDA to ease up on toxicology requirements. Hatching and testing a drug can take more than a decade; Yu and team delivered milasen to Mila in 12 months.

By then, Mila could no longer see or walk. She had frequent seizures. But after milasen, the frequency of her seizures slowed markedly — and significantly decreased in severity. She regained the ability to hold up her body — and could eat without a feeding tube. Mila laughed again during bedtime stories.

“There were so many different things that might seem subtle, but they were a really big deal relative to her life,” Vitarello said. “Her quality of life, and our life as a family, was so much better.”

But Batten disease again took hold. Snuggling Mila in bed one night, Vitarello dreamed that her daughter was pretending to be a jaguar — and then slid off the bed and ran. Awakening in a dark room, Vitarello saw the dream as a message: Mila was ready to be free from pain and confusion. She died days later.

“I’m usually good at finding words, and it’s very hard to find words to describe how much pain there is around losing a child and watching them degenerate,” Vitarello said.

In the ensuing weeks, Vitarello ached to go in Mila’s room. When she finally entered, the sheets and pillows were the same. She dropped to her knees and cried uncontrollably.

Over time, another feeling crept in, one that Vitarello’s parents instilled in her at a young age: gratitude. She still had Azlan, who had long let Mila be the focus. During a quiet car ride with him, Vitarello apologized for not giving him enough attention. “He said, ‘It’s OK, mommy. I know your mind was always on Mila,’” Vitarello said.

Vitarello continued the emotional expeditions into Mila’s room. One day, she arranged her desk by Mila’s window. “While I type, I stop, sit back and notice the light and warmth I now feel in Mila’s room. This is where I want to be,” Vitarello wrote in her blog.

I nspired by milasen, more scientists and doctors have launched custom drug programs. Many of them have come together under an umbrella group that Vitarello helped organize, known as the N=1 Collaborative.

Rather than work in silos, the idea is that N=1 Collaborative members share data, methods, and hard-learned lessons. Yu, who is on the group’s organizing committee along with Vitarello, likened it to open-source internet browsers that sprung up in response to proprietary business models.

“Wouldn’t it be wonderful to see some of that philosophy applied to drug development?” asked Yu.

The N=1 Collaborative had its inaugural workshop only last June. But already more than 30 institutions have joined workshops or contributed in other ways. Vitarello believes the group will lead to breakthroughs and dedicate more scientific brainpower to custom medicines.

On a recent Zoom meeting the collaborative held, her normally polished voice quivered as she emphasized the importance of scaling these medicines. She noted that her daughter’s situation wasn’t unique. Globally, children make up half of the 400 million people with rare disease, the vast majority of whom don’t have treatments.

“We need good science,” she said.

Like Yu, many members entered drug development with what are called antisense oligonucleotides. Antisense drugs have the same chemical backbone, with room for a snippet of genetic code to fix a mutation.

The technology was pioneered by Ionis Pharmaceuticals, and the company’s founder and former CEO, Stanley Crooke, formed his own custom drug outfit. Launched in 2020, the n-Lorem Foundation plans to create medicines for around 50 patients, and the nonprofit’s patient load is expected to grow over time, according to Crooke. Philanthropy allows the organization to provide free medicines, for life.

Still, Vitarello believes academics and nonprofits alone cannot scale custom medicine. Besides the N=1 Collaborative, she’s part of a fledgling group — about which she declined to elaborate on at this stage — that’s exploring ways to reimburse businesses for creating custom medicines.

A recently launched data science company, Quantile Health, has sought to secure insurer reimbursement through a subscription model that’s designed to spread out a personalized medicine’s cost over time. The company’s co-founders include MIT economist Andrew Lo, who has written extensively about financing rare disease drugs.

Reimbursement would spur drug creation — and expand custom medicine access to those who aren’t wealthy, able to raise large sums, or connected to a foundation. Still, even if a drug is covered by insurance, patients can still pay high costs.

“The conversation that needs to be had is how can we look at more equitable access of these gene therapies by reimbursing the cost,” said Rich Horgan, the CEO of Cure Rare Disease. Horgan formed the organization to develop a gene therapy for his brother, Terry Horgan, who has an ultra-rare form of muscular dystrophy. The group, which expanded to create additional custom therapies, relies on philanthropy. It hopes that reimbursement unlocks another funding stream. Additional funding could come from partnering with biotechs on Cure Rare Disease’s programs that may serve a larger population.

There’s also the issue of regulation. As a starting point, the FDA last year issued guidance modeled after milasen, including how to assess whether a drug is working in a single-patient clinical trial that, by its definition, does not include a placebo group. (The agency did not respond to a request for comment.) Vitarello called the guidance a positive step, but said it’s difficult to scale when, for instance, each custom drug requires a 1,000-page document requesting permission to start a clinical trial, or what’s called an investigational new drug application. Yu echoed her sentiments.

“The regulations right now are still trying to fit a square peg into a round hole,” Yu said, adding that the FDA recognizes more change must come. “In five years, when we’re doing RNA medicines, CRISPR medicines, and things like that, it’s going to have to evolve a lot more.”

Vitarello and Yu envision a future where individualized medicine centers pair routine DNA testing with custom drug development. If whole-genome sequencing reveals that a baby needs a novel treatment, work could start in mere days. “Mila’s drug was incredible in terms of its promise,” Vitarello said. “What if it came earlier?”

Boston Children’s Hospital is working toward this goal. During a Zoom tour, Yu popped into a lab where patient blood and skin samples are coaxed into becoming stem cell lines. Stem cells are exposed to a drug compound, indicating how the drug might perform in a person. The lab marked but one stop in the tour of the hospital’s many places and people involved in custom drug development.

Besides milasen, two custom drugs that sprung out of Boston Children’s have reached clinical trials. Plans call for creating more medicines.

This type of drug development requires a shift in mindset, too. Yu said custom medicines erode the boundary between patient and physician. For instance, he collaborates on policy issues with Vitarello, who he said brings lived experience that the FDA wants to hear. Others eagerly listen, as well. After Mila died, Vitarello surrounded herself with rare disease patients. That includes advising families who are in a position she once faced.

“She really gave us a lot of hope,” said Lauren Rosenberg. Vitarello spent many hours on the phone with Rosenberg and her husband after their daughter, Sophie, was diagnosed with an ultra-rare disorder. The family is racing to find a cure. Years earlier, before the diagnosis, the Rosenbergs just so happened to donate to the Vitarello-created Mila’s Miracle Foundation.

F or Vitarello, the end of 2021 brought more immeasurable loss. Her mom, a non-smoker, died of stage 4 lung cancer. Vitarello said her mom wouldn’t want her and Azlan to dwell on the past. It’s a delicate balance between remembering and moving forward.

During a virtual call from Mila’s room, Vitarello placed a stuffed hummingbird on Mila’s bed. She smoothed the sheets that haven’t been changed in a year. “That’s one of the things I couldn’t change,” she said.

This name will appear with your comment

There was an error saving your display name. Please check and try again.

Reporting from the frontiers of health and medicine

You've been selected! Subscribe to STAT+ for less than $2 per day

Unlimited access to essential biotech, medicine, and life sciences journalism

Subscribe to STAT+ for less than $2 per day

Unlimited access to the health care news and insights you need