Tonya Carlone, of Maple Valley, is pushing for FDA approval for an experimental drug that has allowed her 9-year-old son, Gavin, to live a normal life, despite having Duchenne muscular dystrophy. A decision is expected next week.
The mother of a Maple Valley 9-year-old with a rare muscle disorder is lobbying the federal Food and Drug Administration (FDA) for what she says would be a “Christmas miracle” — approval of the first drug to treat the progressive and fatal disease.
Tonya Carlone, 44, has testified before an FDA advisory panel, written letters and emails to media outlets and launched an online petition now signed by more than 5,000 people — all in hopes of helping her son, Gavin, who has Duchenne muscular dystrophy.
She’s trying to sway an FDA decision, expected on Christmas Eve, about whether to approve a drug called drisapersen, which she said has slowed dramatically the progress of Gavin’s disease and allowed him to be a normal kid.
“It’s difficult to enjoy the holiday season when you know this is looming,” said Carlone. “This means everything for you. You’re fighting for your child’s life.”
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The trouble? Results of three randomized clinical trials have raised questions about the effectiveness and safety of the drug, produced by BioMarin Pharmaceuticals and known by the brand name Kyndrisa.
An FDA advisory panel did not provide an up-or-down vote on whether the drug’s risks outweighed the benefits. Instead, the group voted on persuasiveness of each trial, with most members concluding the evidence presented either weakened the case for the drug, or had no effect.
“The current thinking of the primary-review team is that evidence supporting the effectiveness of drisapersen is inconsistent,” the panel wrote.
The FDA is not bound by the decision, but takes the advice into consideration.
That finding was devastating to Carlone, who was among dozens of parents and children who showed up at the panel meeting Nov. 24 in Silver Spring, Md.
“If they want efficacy, it was staring them in the face,” said Carlone.
Such a situation is not unusual, however, said Dr. Caleb Alexander, the head of the FDA panel that considered the evidence.
“It’s not uncommon that the testimony of individuals points one direction and the FDA’s statutory obligations point in another,” said Alexander, who is co-director of the Center for Drug Safety and Effectiveness at Johns Hopkins Bloomberg School of Public Health.
And the agency is bound to follow science, even in the face of compelling human stories, noted Art Caplan, director of the division of medical ethics at New York University’s Langone Medical Center.
“The FDA has to abide by evidence, not anecdote, in approving drugs,” Caplan said.
That’s true even in the case of so-called “orphan drugs” aimed at treating rare diseases that affect fewer than 200,000 patients a year.
But it creates a distressing prospect for families of patients like Gavin, who could lose access to his only option if the drug is not approved.
“I don’t sleep at night, I’ll tell you that,” said Tonya Carlone. She and her husband, Anthony Carlone, 38, also have two daughters, 11 and 6. Growing up, Tonya Carlone had a cousin with Duchenne and she still recalls his suffering and the effect on her family.
Gavin, a fourth-grader at Rock Creek Elementary School, was diagnosed as a toddler with Duchenne muscular dystrophy, a genetic disorder that primarily affects boys, robbing them of the ability to walk starting at about age 8 and putting them in wheelchairs by 12. Eventually, it shuts down breathing and heart function. About 20,000 boys in the U.S. are living with the disease.
When Gavin was almost 6, his parents enrolled him in a clinical trial of drisapersen conducted at British Columbia Children’s Hospital. The results were dramatic, they said. After six months of treatment Gavin could climb stairs properly and pull himself into the family van instead of crawling. His balance grew steady; he even learned to ride a two-wheeled bike.
Those effects were possible with drisapersen, a so-called “exon-skipping” drug that helps bypass a mutation that prevents formation of dystrophin, a crucial protein that protects muscle fibers from injury and deterioration. Genes are made up of exons, which contain instructions for function.
Without the protein, muscles weaken and fail. With the drug, which targets a mutation on exon 51, a truncated form of the protein is formed, restoring function. It may help about 13 percent of the boys affected by Duchenne, according to BioMarin.
Nearly two years into the Canadian trial, however, the research was abruptly halted. Drug giant GlaxoSmithKline had been working with the Dutch firm Prosensa Holding NV to produce the drug. In a late-stage study, it failed to show significant benefits and the research stopped.
Gavin was without the medication for 16 months and the effects were obvious, his mother said. “We could visibly see him start to decline.”
Last January, Gavin was able to enroll in a drisapersen extension sponsored by BioMarin, which acquired Prosensa in an $840 million deal in 2014. The trial is led by Dr. Craig McDonald, a professor of pediatrics and rehabilitation at the University of California, Davis.
Within months, Gavin had regained strength and skill, far different from the other boys with Duchenne whom McDonald has treated during the past 25 years.
“Not only is Gavin running, but he is playing soccer in a manner similar to his teammates, jumping, hopping and running up steep skateboard inclines at the park,” McDonald said. “He is keeping up with his classmates.”
Still the trial results of one-year outcomes were mixed. FDA panel members noted that drisapersen appeared to have little effect on increasing dystrophin levels and that the results had “unimpressive statistical strength.”
There were also questions about adverse events, including injection-site reactions, kidney injury, bruising and blood-clotting problems.
But McDonald said FDA officials limited their review to prespecified analyses that failed to consider new promising information about higher initial doses and long-term effects of the drug.
“Given Duchenne is a fatal and terribly progressive disease, I believe the benefit-risk ratio clearly favors approval of the drug,” McDonald said.
But neither he nor Carlone are willing to predict what the FDA will too. Debra Charlesworth a spokeswoman for BioMarin, said it’s still “too early to tell.”
There may be ways to obtain the drug through a special FDA process known as expanded access, which allows the use of a drug outside a clinical trial. Marketing approval for drisapersen is pending in Europe, but the drug is estimated to cost $300,000 a year, far beyond the Carlones’ ability to pay. If the drug is approved, it paves the way for insurance coverage.
In the meantime, Carlone has joined other parents who’ve turned to citizen advocacy and public relations to influence federal health policy. In 2013, the parents of a Pennsylvania 10-year-old, Sarah Murnaghan, successfully lobbied to change the way lung transplants are allocated in the U.S.
That’s the idea behind the change.org petition directed at the FDA’s Dr. Janet Woodcock, head of drug evaluation and research. “Give our Duchenne boys their Christmas miracle,” it reads.
“It could be a great Christmas — or not,” Carlone said. “I won’t give up, that’s for sure.”