When Griffin Moritz was 10, he experienced what his mother, Debora, called "an explosion" of non-cancerous but life-threatening brain tumors.
They were one aspect of a rare genetic disease called tuberous sclerosis that his family had dreaded, after he grappled with frequent seizures, autism and reddened skin bumps that doctors periodically lasered.
Neurologists could only offer surgery for the growths that blocked the flow of cerebrospinal fluid bathing Griffin's brain and spinal cord. But Griffin wasn't a good candidate for the operation.
So when his mom heard of an experimental medication to shrink the subependymal giant-cell astrocytomas (SEGAs), she raced to enroll her son in a small clinical trial at Cincinnati Children's Hospital Medical Center, 1,800 miles from their home in Scottsdale, Ariz.
Three years after Griffin began swallowing daily doses of the immune-suppressing drug everolimus, called RAD0001 for study purposes, the 13-year-old's brain tumors have nearly disappeared. He's having far fewer seizures. The red angiofibromas on his face have faded. And there's been another bonus. Although Griffin remains nonverbal, "he became more in-the-moment. He's more responsive to things. His eye contact improved and he [is] learning more readily," Debora Moritz said.
"We say it's just been a totally RAD experience," his delighted mother said, playing on the drug's study name. "This is so huge. We think it is the Rosetta Stone for so many disorders."
Such striking results from a Phase I-II study of 28 patients led the FDA Saturday to grant fast-track approval to everolimus, which will be marketed as Afinitor, as an alternative to surgery for tuberous sclerosis patients. It's the first-ever approved treatment for the disorder.
"It's what we hoped for," said Dr. David Neal Franz, senior author of the study published in this week's issue of the New England Journal of Medicine.
The clinical trial, funded by the drug manufacturer Novartis, found that tumors shrank by at least 30 percent in 21 of the patients and by at least 50 percent in nine patients.
The most marked and fastest shrinkage occurred in the first three months of treatment, but the effects were sustained. Franz, a professor of pediatrics and neurology at the University of Cincinnati College of Medicine, said 75 percent of patients saw their tumors reduced by at least 30 percent in volume, and all participants had some response to the drug. Without it, he said, the buildup of water in the brain can cause hydrocephalus, which can then start to invade brain tissue. "If they're not treated, these grow at variable rates," he said. "A person may not live more than a few years."
"It is fantastic. I'm very glad it's come through this quickly," said pediatric neurologist Dr. Candida Brown, a tuberous sclerosis specialist at Children's Hospital & Research Center Oakland in northern California.
"Up until recently, we didn't have any kind of treatment. We just had symptomatic treatment for the effects of these tumors that grow throughout the body. We have a drug that is going to make a significant difference in the lives of these people."
FDA approval of an oral drug was welcome news for the community of about 40,000 Americans with tuberous sclerosis, who develop benign tumors of the kidneys, lungs, heart and skin. About 1 in 6,000 people are born with the disorder, and up to 20 percent of them develop brain tumors.
About 30 percent of people with SEGAs need surgery, but even in highly skilled hands, surgery to remove the tumors is risky, and if the operation doesn't get all the tumor tissue, the growths come back. The disorder also causes seizures in about 90 percent of patients.
Franz said about one-third of TS patients are severely affected and have a host of problems, including learning difficulties; about two-thirds are of normal intelligence.
Investigators from Cincinnati Children's Hospital decided to experiment with everolimus, a drug approved earlier for kidney cancer, because it inhibits a protein involved in both the growth of kidney cancer cells and SEGAs.
The study was an open-label trial, in which all patients received the medication. The participants, who had to be at least age 3, were mostly children and teens, with 22 younger than 18. There were 17 males and 11 females, whose average age was 11. Although the study initially was designed to last six months, investigators continued treating the patients and monitoring the sizes of their tumors using MRI. The mean treatment duration was 21.5 months.
The medication had secondary benefits for patients with seizures. In the 16 patients for whom researchers had 24-hour electroencephalograms recording brain waves, nine experienced fewer seizures while taking the medication. Seizures were unchanged in six patients; one experienced an increase in seizure frequency.
But the benefits of Afinitor come with serious side effects. Because the drug suppresses the immune system, it can make patients more prone to infections, and the FDA-approved patient information sheets warn of potential pneumonia or bacterial, fungal or viral infections.
Drug reactions reported by study participants included sinusitis, mouth ulcers and sores, and low white blood cells, as well as vomiting, dizziness, pneumonia, bronchitis and tooth infections.
Franz's study continues; he hopes to have five years of Afinitor data in tuberous sclerosis. Because so many of his clinical trial patients had fewer seizures on the pills, he's studying their potential in epilepsy patients.
He also said that some of the same pathways that are involved in TS are involved in many cancers and other diseases such as Alzheimer's, Parkinson's and Huntington's. What these all have in common is excessive accumulation of protein toxic to brain cells.
Franz also said he believes the drug could help with behavioral learning problems, because the same pathway is involved in "how you form memory and learning."
But, for now, while the drug is about to be marketed to patients with brain tumors, he and those who treat tuberous sclerosis patients are happy to offer a new treatment tool.
"It's not a cure," said Oakland's Brown, who is leading an advanced study of the drug, "but it's a very good treatment."