A recently approved cystic fibrosis drug is offering hope to at least half of the 30,000 individuals affected by the life-threatening, genetic disease, including 18-year-old Mary Beth Mast.
A resident of Fredericksburg in Wayne County, Ohio, Mary Beth has felt much better since enrolling in the clinical trial for Orkambi 2 years ago.
“I have more energy and I’ve been able to gain about 10 lbs.,” she said. “I just feel a lot healthier.”
The ability to be more active and gain weight is significant for CF patients since the disease causes thick, sticky mucus to build up in their lungs and pancreas, limiting their ability to breathe and absorb food and key nutrients.
“Orkambi is an exciting drug for patients with cystic fibrosis, partly because it actually treats the defect that causes CF,” said Dr. Greg Omlor, director of Akron Children’s Lewis H. Walker Cystic Fibrosis Center. “Most of the previous drugs treat the problems that CF cause, but not the basic defect. The other exciting thing about Orkambi is that it is useful in patients with the most common mutation and therefore will treat up to 50% of our patients.”
Mary Beth’s mom, Ida Mast, hopes 2 of her other children with the same CF mutation – Jaylon and Angela – will also be able to benefit from the drug once it’s approved for children under 12.
“We are very excited about the possibility of life extension,” Ida said. “It is an exciting advancement for us and the entire CF community.”
About cystic fibrosis
CF is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This protein functions as a chloride channel that helps the body maintain the proper balance of salt and water within a cell.
A mutation of CFTR disrupts the salt and water balance, leading to the production of thick mucus and the excessive loss of salt in sweat. While there are hundreds of mutations that can cause CF, the most common is the delta F508 mutation.
Orkambi, which is manufactured by Vertex Pharmaceuticals, addresses this mutation by combining a previous drug, Kalydeco, with another compound. Kalydeco, which was FDA approved in 2012, was the first drug aimed at counteracting the defective protein that causes cystic fibrosis.
“Kalydeco treats the basic defect of CF, but for only a specific type of mutation that affects about 15% of patients,” Dr. Omlor said.
Dr. Omlor estimates that 40-45% of his pediatric CF patients, 50% of his adult CF patients, and all of his Amish patients have 2 copies of the delta F508 mutation.
According to Dr. Omlor, people who’ve received Orkambi experienced a small increase (2.6%-3.0%) in the volume of air they could exhale in the first second of a forced exhalation.
This pulmonary function parameter is important because it’s predictive of survival for CF patients, who currently have a median survival rate of 40.7.
Perhaps the most noticeable change was a decrease in the number of times patients had a flare-up of their pulmonary disease.
“This has significant medical implications because this is often when patients lose pulmonary function and do not fully regain it,” said Dr. Omlor. “There is also a social implication because the treatment for a flare-up often means a stay in the hospital with IV antibiotics. Avoiding hospitalization is a big deal for patients. ”
And like Mary Beth, patients taking Orkambi reported feeling better compared to those who weren’t.
“There was also increased body weight in patients on Orkambi,” Dr. Omlor said. “This is important because weight is associated with pulmonary function. In other words, those patients with better weight were also more likely to have better pulmonary function.”
The biggest side effects of Orkambi are a feeling of chest tightness or a sense of difficulty breathing and elevation of liver enzymes.
“The feeling of chest tightness was not unexpected because previous studies showed this with one of the drugs in the study,” said Dr. Omlor. “The liver elevations decreased when the medication was stopped. It is recommended that patients get liver enzymes done before they start the medication, every 3 months for the first year and then annually after that.”
Another concern with Orkambi is interaction with other medications. CF patients frequently take medications to treat bacterial infections, fungal infections and acid reflux as well as to decrease inflammation. Some antidepressant medications and hormonal birth control medications may also have an interaction with Orkambi.
“In most cases the doses of the medications may need to be adjusted,” said Dr. Omlor. “In some cases other medications are suggested, if possible, such as with the antifungal medications and antibiotics. For the hormonal-based birth control medications, an additional form of birth control is recommended.”
Perhaps most importantly, the approval of Orkambi and Kalydeco may lead to the development of similar drugs.
“Kalydeco and Orkambi are a proof of concept that this type of therapy is effective and can be approved by the FDA,” Dr. Omlor said. “This will encourage pharmaceutical companies to continue research on this class of drugs. The newer drugs could be more potent and/or with fewer side effects.”
But everything comes with a cost. Orkambi costs about $295,000 for a year’s supply.
“If the insurance companies don’t pay for it then very few families can afford the cost, so they might not use it even though they are a candidate for it,” Dr. Omlor said. “This will have significant impact on the Amish families that don’t have the big insurance companies that our other patients do.”