Taking a shot: An orphan drug trial that drew an international crowd of patients nears its end

When Sarah Morrell was first diagnosed with Morquio syndrome, a rare, incurable disease that crippled her joints and deformed her vertebrae, her family never expected the illness would cause her to travel halfway around the world to have an experimental treatment derived from the stem cells of Chinese hamster ovaries injected into her veins.

For starters, the mere idea that there would be a treatment for Morquio defied convention. The disease is so rare – health experts estimate it occurs in just one of every 200,000 births – there was little motivation for pharmaceutical companies to conduct the expensive research and testing needed to develop a new drug.

That changed last year, when Sarah, 18, and her dad, Ben Morrell, moved from their home in Wanganui, New Zealand to Walnut Creek, California to take part in this experimental treatment at Children’s Hospital Oakland. The new drug, called Vimizim, is classified as an orphan drug – a term used for drugs that treat diseases too rare to attract large pools of research funding. The classification allows drug companies who make orphan drugs to shortcut some of the US Food and Drug Administration’s red tape in order to expedite approval.

Vimizim, which is currently under review for FDA approval, is derived from Chinese hamster ovary cells (which are widely used in biological research) and is the first viable treatment for Morquio syndrome – a debilitating disease where the body lacks the enzymes necessary for healthy growth. Without a previous treatment to base their hopes on, patients have traveled from all around the world to take a chance on this obscure drug with no guarantee that it will work.

“My friends were joking that I would turn green,” said Sarah. “But I haven’t yet.”

Children’s Hospital is just one of a handful of sites worldwide that were chosen by BioMarin Pharmaceuticals Inc., the maker of Vimizim, to participate in the trial. As a result, the narrow hospital room where patients come for the treatment is bustling with a variety of skin tones, accents and socioeconomic backgrounds.

Mr. Morrell, for one, said he saw it as “a chance to do something to help Sarah,” and maybe to help other people as well since the trial could lead to wide availability of a treatment. “It’s like helping mankind, in a way,” he said.

The effects of the disease, which stunts growth and weakens and deforms developing joints and limbs, can vary widely among patients and change drastically over time. In its early stages, the disease attacks the growth process of otherwise healthy children. Wrists and ankles twist into themselves, leaving some patients crippled. Because patients lack enzymes that allow their cells to process certain nutrients, unprocessed carbohydrates can accumulate and cause complications in their livers, eyes, joints and respiratory systems. As the disease progresses, these accumulations can make it increasingly difficult for patients to see, hear and breathe. One of the key goals of the new drug is to help patients retain or improve their mobility, which is usually lost, as hipbones are contorted and spines curved.

Because Morquio is genetic, many of the families participating in the study have more than one child affected by the disease. The O’Donnells, from Huntington Beach, California, have two daughters with Morquio: Evie, 7, and Sadie, 3. Even if neither parent has the disease, they each have to be carriers of the recessive gene in order for their child to develop Morquio. Michael O’Donnell, Evie and Sadie’s dad, said he and his wife’s first child wasn’t diagnosed with Morquio until after their second was born, so they didn’t realize they were both carriers of the gene until Evie and Sadie were already born with it.

Mr. O’Donnell said it took over a year to find a diagnosis for Evie after he and his wife noticed abnormalities in her growth.

“We thought it was some bone displacement and that it wasn’t going to get worse so we weren’t worried about having another child. But it got worse. I started noticing her hands were very unique,” Mr. O’Donnell said. After failing to get a diagnosis from several doctors, O’Donnell did his own research online. That’s when he heard about Morquio syndrome.

“I found a description of Morquio and had that tunnel vision. It was like, ‘This is it. Wow. This is what my daughter has,’” he said.

The trial drug hopes to curb the effects of Morquio through what is called enzyme replacement therapy. It basically infuses the body with the missing enzymes it needs to “get patients breathing better, moving better, and have more energy,” according to Dr. Paul Harmatz, who administers the trial at Children’s. The treatment involves a weekly IV infusion that takes one hour for nurses to prepare and four hours for patients to receive. It could take decades for doctors and participants to know if the drug will address some of the more dramatic side effects of Morquio, like shortened life expectancy.

Though some patients have allergic reactions to the treatment, Dr. Harmatz has so far been able to temper those reactions with antihistamines. The bigger concern is a patient’s heart rate, which can be affected by the infusion and cause complications. Heart rate monitors ping in the background constantly as nurses keep an eye on Sadie O’Donnell’s fluctuating heart rate.

Because Sadie is so young, Harmatz says, she is more susceptible than her older sister to complications from the treatment – but she is also more likely to benefit. Since her joints and limbs have yet to finish growing, there’s a better chance that the new drug can work to correct growth abnormalities before they happen.

“We weren’t sure if we wanted to do the study because it’s pretty risky,” admitted Mr. O’Donnell. “But we just felt we had to try something because it’s a progressive disease.”

As the trial nears its end, patients are hoping to hear this month whether the drug gets approved by the US Food and Drug Administration. Approval could allow patients to receive the treatment in their hometowns.

But the end of the trial isn’t the end of the story. Treatment with Vimizim can cost up to $1 million a year – a prohibitive expense for many patients and their families. Dr. Harmatz said elements of the Affordable Care Act should help with this because insurance companies are now banned from discriminating against people with pre-existing conditions and imposing spending caps on their customers.

“It’s a huge breakthrough for these patients,” Harmatz added.

With Morquio, finding the money for treatment has been an ongoing problem. Though BioMarin covers the cost of treatment and transportation during the trial, parents still have to take time out of work to take their children for treatment. Mr. Morrell had to quit his job in New Zealand to move to the US with his daughter.

“We’ve extended our mortgage, borrowed money,” Morrell said. “And (my wife) still works back home.”

While many families are thrilled by the idea of receiving treatment at home, many acknowledged that they are going to miss the support and friendship that has formed among the trial participants.

“It’s bittersweet because it’s what we’ve strived for, to get this treatment approved for these kids,” said Bertha Kallas, whose daughter, Ariana Kallas, 8, is a trial participant. “But it’s sad to not be around the other kids and moms. We’re best friends.”

For many participants, the relationships they’ve formed with these other Morquio patients is an unexpected take-away from the trial.

When asked about her experience in the study, Kianna White, 18, who flies to Oakland every week from Arizona, almost immediately began talking about the fellow patients and nurses she’s met since she joined a year and a half ago.

“We’re called the A-team because we’re all A-list preferred members at the airport,” White said, referring to the frequent flyer miles racked up by the families that take weekly flights into Oakland from their hometowns to receive treatment. This past year, a couple of the participants cashed in their award miles for a free group trip to Disneyland.

Looking around the cramped hospital room at the parents and children awaiting treatment, White smiled.  “We’re family,” she said.