Helpful drug for cystic fibrosis patients
Rick Cissna, born in 1962, was always sick as a kid. He didn't understand why his lungs were always full of goop, why he couldn't recover from colds like his friends did, why eating made him sick. At 16, he was finally diagnosed: He had cystic fibrosis, an often-deadly disease caused by a genetic defect.
Soon, he became a patient of Dr. Bonnie Ramsey, a pediatrician at Seattle Children's. Ramsey was just starting what would become three grueling decades fighting the devastating disease, which clogged young lungs with mucus and often killed patients before adulthood.
Thirty years later, Cissna's and Ramsey's paths would cross again in a most wonderful way.
It came about because of a little blue pill called Kalydeco, recently approved by the federal Food and Drug Administration (FDA) after a key trial led by Ramsey showed striking results.
Although it helps only a small subset of those who have cystic fibrosis, it is the first drug to target the disease's genetic cause, not just its symptoms.
"I don't think you can overstate how dramatic this result is," said Dr. Peter Mogayzel, director of the Cystic Fibrosis Center at Johns Hopkins.
Not only will it give powerful help to a small percentage of patients, he said, "it also heralds the beginning of a new era" of therapies for other cystic-fibrosis patients.
Kalydeco (kuh-LYE-de-co) rests on scientific work begun decades ago on the human genome.
A "personalized" drug, it works only for a certain genetic mutation — the one Cissna has.
Cystic fibrosis (CF), a genetic disease, occurs when people inherit two copies of a defective gene — one from each parent. About 30,000 people in the United States have the disease; an additional 10 million or so — about one in 31 Americans — have one copy of the defective gene.
According to the FDA, it is the most common fatal genetic disease for Caucasians.
Targets the lungs
Although Cissna had a relatively mild case, he experienced many of the disease's symptoms.
Because the genetic defect disturbs the body's salt balance, people with CF can't keep their lungs and airways clear. The lining of their lungs dries out and mucus thickens, clogging airways, inviting infections, pneumonia and scar tissue.
People with CF typically die from lung failure, although the disease affects many other organs and the digestive tract, making it hard for people with CF to get enough nutrition. Often, their fingers show a distinctive club shape, and males often are infertile.
Currently, the average life span is about 39 years.
When Cissna and Ramsey first met, about 1980, the average life span was about 18.
123
At 21, Cissna left her care, and Ramsey lost track of him, hoping he was still alive, but fearing the worst. During the next three decades, Ramsey helped develop important treatments that allowed patients to live longer.
More than 10 years ago, she began collaborating with the company that originally developed the drug. In 2009, she began the trial that led to Kalydeco's approval.
She didn't know that her former patient had volunteered for the study, received the drug — not the placebo — and had quickly improved.
When she found out, she recalled, "I was ecstatic."
Later, she saw a brief video of Cissna. He wasn't coughing. He was running.
"I just started crying. I was just so happy."
Earlier this month, Ramsey and Cissna met again. In a hallway at the Children's Research Institute where Ramsey works, they threw their arms around one another.
Both were elated.
Cissna because Kalydeco has helped him breathe, eat and have more energy. And Ramsey, because finally, there was a "game changer" in her long quest to stop CF's relentless destruction.
"It really is one of the most exciting things that I've been involved with in my career," said Ramsey, director of the Center for Clinical and Translational Research at Children's. "It's wonderful to be able to make this impact on someone's life."
Kalydeco, said Dr. Margaret Hamberg, an FDA commissioner, "is an excellent example of the promise of personalized medicine — targeted drugs that treat patients with a specific genetic makeup."
Outlook bleak
In the early years of Cissna's life, the outlook for most kids with CF was grim. Sequencing the human genome was just a dream, and doctors had little to offer beyond oral antibiotics and teaching parents how to pound their child's back to loosen CF's thick mucus.
In those days, most kids were repeatedly hospitalized until lung failure finally sapped their lives.
Many people became aware of the disease's toll through a moving 1982 memoir by sports writer Frank Deford, detailing the life of his daughter, who died in 1980 at age 8.
"Alex: The Life of a Child," and the 1986 TV movie based on it, made millions of readers and viewers cry as they learned about Alex's struggles. In those years, most children were diagnosed through their very salty sweat.
Now, newborns, who benefit from early diagnosis, are screened through a blood draw from the heel. Last year, Washington's screening found 17 newborns with CF.
CF involves 1,800 mutations; any two create the disease.
These days, virtually all CF patients know their mutation, Ramsey said.
Most have at least one copy of a particular mutation, an improperly folded protein trapped inside the cell, unable to reach the surface to do its duty as a salt pump. The protein Kalydeco targets, on the other hand, has made it to the surface, where the drug can "turn it on."
Kalydeco is the "destination in a long journey" that began with the identification of the CF gene in 1989, The New England Journal of Medicine recently noted.
To get there, it needed sustained effort and investment, collaboration of academic and industry researchers and a research network — the Cystic Fibrosis Therapeutics Development Network, created by Ramsey with support from the Cystic Fibrosis Foundation.
The development of Kalydeco, Ramsey said, is "step one" in finding drugs to fix the more common defect.
"I think this gives us a clear path to future research," says Ladd Moore, co-president of the Washington chapter of the CF foundation. His sister, Lissy Moore, died of CF in 1998 at age 15.
Treating symptoms
In the early 1980s at Seattle Children's, Ramsey's patients often spent half their short lives in the hospital.
Despite being what Ramsey recalled as "a very sick kid," Cissna enrolled in her very first study.
Cissna "was one of my dearest patients," she said. "The age he was diagnosed was when we were losing most patients."
As Cissna grew up, he and others with CF were helped by innovations, many developed by Ramsey and her colleagues, such as nebulizers and inhaled antibiotics to help quell life-threatening lung infections.
But always, the drugs treated only symptoms.
High hopes for gene therapy were dashed in 2005, when, after 15 years and at least $40 million, a large trial by a Seattle biotech failed to find benefit.
Through it all, Cissna just kept going. He married, adopted two kids, and became a teacher. But denial was getting harder to sustain.
Over the years, he had recurrent lung infections, a collapsed lung and repeatedly developed resistance to antibiotics. Insurance paid for a $14,000 inflating vest to help him clear his airways. He enrolled in the Kalydeco trial more than two years ago. A week after starting to take the little pills, Cissna had a sudden realization: "Ohhhh — I was not on the placebo!"
For the first time, he began gaining weight. Just like normal people do. "My friend said, 'Congratulations! You're now just a middle-aged, overweight guy!' " Now, his wife, Kathy, says it's as though he doesn't have CF anymore. "It's amazing."
Kalydeco doesn't "cure" CF. And it costs $294,000 a year. That means nearly $400 for each blue pill, taken twice a day. Dawn Kalmar, spokeswoman for the drug's Cambridge-based company, Vertex, says it will help many patients with costs.
Ramsey said she expects insurers will pay for this FDA-approved treatment. Parents in online chat rooms note that in some cases, Kalydeco costs less than IV antibiotics, respiratory therapy and hospitalization.
Soon, he became a patient of Dr. Bonnie Ramsey, a pediatrician at Seattle Children's. Ramsey was just starting what would become three grueling decades fighting the devastating disease, which clogged young lungs with mucus and often killed patients before adulthood.
Thirty years later, Cissna's and Ramsey's paths would cross again in a most wonderful way.
It came about because of a little blue pill called Kalydeco, recently approved by the federal Food and Drug Administration (FDA) after a key trial led by Ramsey showed striking results.
Although it helps only a small subset of those who have cystic fibrosis, it is the first drug to target the disease's genetic cause, not just its symptoms.
"I don't think you can overstate how dramatic this result is," said Dr. Peter Mogayzel, director of the Cystic Fibrosis Center at Johns Hopkins.
Not only will it give powerful help to a small percentage of patients, he said, "it also heralds the beginning of a new era" of therapies for other cystic-fibrosis patients.
Kalydeco (kuh-LYE-de-co) rests on scientific work begun decades ago on the human genome.
A "personalized" drug, it works only for a certain genetic mutation — the one Cissna has.
Cystic fibrosis (CF), a genetic disease, occurs when people inherit two copies of a defective gene — one from each parent. About 30,000 people in the United States have the disease; an additional 10 million or so — about one in 31 Americans — have one copy of the defective gene.
According to the FDA, it is the most common fatal genetic disease for Caucasians.
Targets the lungs
Although Cissna had a relatively mild case, he experienced many of the disease's symptoms.
Because the genetic defect disturbs the body's salt balance, people with CF can't keep their lungs and airways clear. The lining of their lungs dries out and mucus thickens, clogging airways, inviting infections, pneumonia and scar tissue.
People with CF typically die from lung failure, although the disease affects many other organs and the digestive tract, making it hard for people with CF to get enough nutrition. Often, their fingers show a distinctive club shape, and males often are infertile.
Currently, the average life span is about 39 years.
When Cissna and Ramsey first met, about 1980, the average life span was about 18.
123
At 21, Cissna left her care, and Ramsey lost track of him, hoping he was still alive, but fearing the worst. During the next three decades, Ramsey helped develop important treatments that allowed patients to live longer.
More than 10 years ago, she began collaborating with the company that originally developed the drug. In 2009, she began the trial that led to Kalydeco's approval.
She didn't know that her former patient had volunteered for the study, received the drug — not the placebo — and had quickly improved.
When she found out, she recalled, "I was ecstatic."
Later, she saw a brief video of Cissna. He wasn't coughing. He was running.
"I just started crying. I was just so happy."
Earlier this month, Ramsey and Cissna met again. In a hallway at the Children's Research Institute where Ramsey works, they threw their arms around one another.
Both were elated.
Cissna because Kalydeco has helped him breathe, eat and have more energy. And Ramsey, because finally, there was a "game changer" in her long quest to stop CF's relentless destruction.
"It really is one of the most exciting things that I've been involved with in my career," said Ramsey, director of the Center for Clinical and Translational Research at Children's. "It's wonderful to be able to make this impact on someone's life."
Kalydeco, said Dr. Margaret Hamberg, an FDA commissioner, "is an excellent example of the promise of personalized medicine — targeted drugs that treat patients with a specific genetic makeup."
Outlook bleak
In the early years of Cissna's life, the outlook for most kids with CF was grim. Sequencing the human genome was just a dream, and doctors had little to offer beyond oral antibiotics and teaching parents how to pound their child's back to loosen CF's thick mucus.
In those days, most kids were repeatedly hospitalized until lung failure finally sapped their lives.
Many people became aware of the disease's toll through a moving 1982 memoir by sports writer Frank Deford, detailing the life of his daughter, who died in 1980 at age 8.
"Alex: The Life of a Child," and the 1986 TV movie based on it, made millions of readers and viewers cry as they learned about Alex's struggles. In those years, most children were diagnosed through their very salty sweat.
Now, newborns, who benefit from early diagnosis, are screened through a blood draw from the heel. Last year, Washington's screening found 17 newborns with CF.
CF involves 1,800 mutations; any two create the disease.
These days, virtually all CF patients know their mutation, Ramsey said.
Most have at least one copy of a particular mutation, an improperly folded protein trapped inside the cell, unable to reach the surface to do its duty as a salt pump. The protein Kalydeco targets, on the other hand, has made it to the surface, where the drug can "turn it on."
Kalydeco is the "destination in a long journey" that began with the identification of the CF gene in 1989, The New England Journal of Medicine recently noted.
To get there, it needed sustained effort and investment, collaboration of academic and industry researchers and a research network — the Cystic Fibrosis Therapeutics Development Network, created by Ramsey with support from the Cystic Fibrosis Foundation.
The development of Kalydeco, Ramsey said, is "step one" in finding drugs to fix the more common defect.
"I think this gives us a clear path to future research," says Ladd Moore, co-president of the Washington chapter of the CF foundation. His sister, Lissy Moore, died of CF in 1998 at age 15.
Treating symptoms
In the early 1980s at Seattle Children's, Ramsey's patients often spent half their short lives in the hospital.
Despite being what Ramsey recalled as "a very sick kid," Cissna enrolled in her very first study.
Cissna "was one of my dearest patients," she said. "The age he was diagnosed was when we were losing most patients."
As Cissna grew up, he and others with CF were helped by innovations, many developed by Ramsey and her colleagues, such as nebulizers and inhaled antibiotics to help quell life-threatening lung infections.
But always, the drugs treated only symptoms.
High hopes for gene therapy were dashed in 2005, when, after 15 years and at least $40 million, a large trial by a Seattle biotech failed to find benefit.
Through it all, Cissna just kept going. He married, adopted two kids, and became a teacher. But denial was getting harder to sustain.
Over the years, he had recurrent lung infections, a collapsed lung and repeatedly developed resistance to antibiotics. Insurance paid for a $14,000 inflating vest to help him clear his airways. He enrolled in the Kalydeco trial more than two years ago. A week after starting to take the little pills, Cissna had a sudden realization: "Ohhhh — I was not on the placebo!"
For the first time, he began gaining weight. Just like normal people do. "My friend said, 'Congratulations! You're now just a middle-aged, overweight guy!' " Now, his wife, Kathy, says it's as though he doesn't have CF anymore. "It's amazing."
Kalydeco doesn't "cure" CF. And it costs $294,000 a year. That means nearly $400 for each blue pill, taken twice a day. Dawn Kalmar, spokeswoman for the drug's Cambridge-based company, Vertex, says it will help many patients with costs.
Ramsey said she expects insurers will pay for this FDA-approved treatment. Parents in online chat rooms note that in some cases, Kalydeco costs less than IV antibiotics, respiratory therapy and hospitalization.
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