Two large clinical trials co-led by a Seattle researcher find that a new drug may help nearly half of people with cystic fibrosis — and reduce the leading cause of death from the disease. Paige Ellens, 17, of Lynden, is among the first to benefit.
When Paige Ellens was diagnosed with cystic fibrosis as a newborn in 1998, Seattle doctors were quick to reassure her parents that there was hope for patients with the life-threatening genetic disorder.
Even then, 17 years ago, there were inklings that research might one day produce a treatment that could target the underlying cause, not just the symptoms of the disease that causes thick, sticky mucus to build up in the lungs, making it hard to breathe.
“It was devastating, but I just remember that I was going to get to watch her grow up to be big,” recalled Paige’s mom, Sharla Ellens, 47, of Lynden, Whatcom County. “Our surgeon assured us that we would find a cure in her lifetime.”
No one’s calling it a cure, but results of two large clinical trials co-led by a Seattle researcher find that a new drug may successfully treat the problem protein in nearly half of people with cystic fibrosis — and reduce the leading cause of death from the disease by 40 percent.
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“It is a breakthrough,” said Dr. Bonnie Ramsey, a professor of pediatrics at the University of Washington School of Medicine and the Center for Clinical and Translational Research at Seattle Children’s Research Institute.
“This is the beginning of effective therapy for cystic fibrosis associated with the most common mutant form of CFTR,” wrote Dr. Pamela Davis, dean of the school of medicine at Case Western University, in an editorial that accompanies the study published Sunday in the New England Journal of Medicine. The disease is caused by mutations in the gene that encodes the problem protein — the cystic fibrosis transmembrane conductance regulator (CFTR).
How the drug helps
Ramsey is one of four lead authors of two Phase 3 clinical trials that confirmed that Orkambi, a new drug from Vertex Pharmaceuticals, can help people age 12 and older with two copies of the most common mutation, known as F508del. Vertex helped fund the trials.
The trial results were part of the evidence that led a federal advisory committee last week to recommend approval of Orkambi by the Food and Drug Administration. In a 12-to-1 vote, the panel agreed that the drug was safe and effective enough to use. The FDA’s decision is expected July 5.
The trials — which studied more than 1,100 cystic-fibrosis patients from six countries between April 2013 and April 2014 — showed that Orkambi helped achieve a 3 percent improvement in lung function over placebo.
“Even though it was only a 3 percent change, once that change happened, there wasn’t a dramatic bump up, but it was absolutely rock solid for 48 weeks,” Ramsey said.
In addition, the drug reduced pulmonary exacerbations by 40 percent, dramatically cutting those sudden and life-threatening declines in lung function. Paige was hospitalized four or five times in the past three years with these debilitating episodes. But with the drug that requires nine pills every day, that’s gotten much better.
“This is the healthiest I’ve ever been in my life,” said Paige, a junior at Lynden Christian School who managed its soccer team last fall and sings in campus musicals.
Who might benefit
Orkambi is intended for the 14,000 cystic- fibrosis patients in the U.S. with two copies of the defective gene. Initially, though, the drug would be used only in the 8,500 people who are older than 12. Tests are being conducted in children as young as 6, Ramsey said, and the eventual hope is that Orkambi may be used in infants with cystic fibrosis soon after diagnosis.
It’s only the second drug in the world that targets the underlying cause of the disease. Vertex also makes the first such drug, called Kalydeco, but it’s only applicable to about 4 percent of the 30,000 cystic fibrosis patients in the U.S.
Orkambi combines Kalydeco, known generically as ivacaftor, with an experimental drug called Lumacaftor, which is not approved by the FDA.
Together, the two medications work to correct the genetic defect by allowing the protein within the cell to fold correctly and rise to the surface — and work properly to move sodium in and out of the cell, Ramsey said.
“It’s a very complicated process to make this protein,” she said. “It has to fold up in a certain way and, as it folds, it has little sugars on the outside to stabilize it and then it has to get moved to the surface, where it works.”
Separately, the two drugs don’t have a very strong effect on most cystic-fibrosis patients, research has shown. Kalydeco alone showed a 10 percent gain of function, but only in the select group of patients, Ramsey noted.
Together, though, the two drugs could become a primary treatment — and a big profit boost for Vertex. Dr. Ronald Hsu, an analyst at the firm Sanford C. Bernstein, estimated Orkambi could generate $2.2 billion in sales by 2018, increasing total Vertex revenue to $5 billion that year.
Huge interest in trials
Paige is one of about 25 Washington state patients who participated in the trials. There was so much interest in the treatment that doctors told Sharla Ellens they resorted to pulling names out of a hat.
“Her name was the first one drawn,” Sharla Ellens said.
The trial tested changes in the amount of air a patient can blow from his or her lungs in one second. Orkambi increased that volume by 3 percent overall, but it also cut life-threatening pulmonary exacerbations by 40 percent.
For Paige and others, the drug offers hope after a lifetime of daily lung treatments, dozens of medications and frequent hospitalizations.
“She doesn’t cough like she used to cough,” Sharla Ellens said. “For the last three years, her lung functions have been as good as a normal 17-year-old’s.”
Officials with the Cystic Fibrosis Foundation said they have supported the drug’s development. Despite improvements in care, 90 percent of deaths in people with the disease are caused by declining lung function. In 2013, the median age of death from cystic fibrosis was 27.5, the group told the FDA.
“We are encouraged by the FDA advisory committee’s recommendation to approve Orkambi,” said Laurie Fink, a spokeswoman for the Cystic Fibrosis Foundation. “We know that our mission is as urgent as ever — ensuring that all people with CF have access to the therapies and the support they need to stay healthy and lead fulfilling lives.”
There’s a worry on the horizon, however, for patients like Paige: the potential cost of the drug. She will continue to receive Orkambi from Vertex for free as the drug undergoes FDA review.
But if it’s approved, the new drug could cost between $250,000 and $300,000 a year, according to Geoff Porges, an analyst at Sanford C. Bernstein.
The medication should be covered by the family’s health insurance. Paige is covered under Washington state’s Apple Health plan, through Sharla Ellens’ teaching job and father Eric Ellens’ work as a general contractor. But, Sharla Ellens said, what if it’s not?
“I’m just literally not going to let myself think of that,” she said. “We have a lot of people who pray for us. We believe that God has a special plan for Paige and maybe this is it.”