In October 2019, the U.S Food and Drug Association (FDA) authorized a new era in cystic fibrosis (CF) treatment. For the first time, the FDA has approved an oral medication that targets a gene defect responsible for approximately 90% of the 80,000 CF cases worldwide.
The new drug, TRIKAFTA, was approved after a series of landmark clinical trials – including research conducted at the UT Southwestern Cystic Fibrosis Clinic – in which patients with one or more Phe508del gene mutation experienced dramatic positive outcomes.
Significantly improved lung function at four weeks, which was sustained through 24 weeks
- Reduced lung flare-ups by 63%
- Decreased the amount of salt lost through sweating
- Improved patients' short-term quality of life and respiratory symptom scores
In some cases, the drug has been so effective that patients have been removed from the lung transplant list. However, TRIKAFTA is not curative and not all patients will experience similar results. While generally considered safe, long-term research is needed to understand potential side effects of the drug over years of treatment.
TRIKAFTA is an oral drug, which is a major shift from the time-consuming nebulizer therapies people with CF are accustomed to. It is currently approved for people 12 and older with one or more Phe508del gene mutation.
For these people, the drug has potential to turn a once fatal disease into a more manageable condition – and hope for more effective therapies for patients with other mutations.
The latest research behind the new drug
Since genetic mutations were found in the 1980s to be the cause of CF, a condition that causes thick secretions in the lungs and other organs, more than 2,000 mutations have been discovered. Researchers around the world have developed previous single- and combo-drug therapies – none of which have been effective for as many people as TRIKAFTA.
The UT Southwestern Cystic Fibrosis Center is accredited by the CF Foundation. As such, we participate in many CF clinical trials – including the studies that led up to FDA approval of TRIKAFTA.
In the trial sponsored by Vertex Pharmaceuticals and cited in the New England Journal of Medicine, I served as a lead author.
Just over 400 people with CF across 115 sites around the world were randomized to receive either a placebo or TRIKAFTA. These patients were 12 and older and had one copy of the Phe508del mutation along with a second one that’s been termed a minimal function mutation.
Patients who took TRIKAFTA experienced such positive results that all participants including those on placebo were allowed to roll over into an open label study to have the opportunity to receive the drug.
We also participated in a second trial, the results of which were published in The Lancet. That study included people with CF with two copies of the Phe508del mutation, which affects approximately 50% of patients with CF in the U.S. This study also showed overwhelmingly positive outcomes.
How the drug works
TRIKAFTA is a combination of drugs elexacaftor, tezacaftor, and ivacaftor. It is a CFTR modulator therapy – while not an actual gene therapy, this type of drug targets the downstream effects of the Phe508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
Unlike previously available modulator therapies, TRIKAFTA is the first approved three-drug combo that targets the Phe508del mutation, where the protein improperly folds, gets stuck in the cell, and ultimately degrades there without reaching the surface to function.
In the combo drug, two of the drugs work together to stabilize that protein folding and allow the protein to reach the surface of the cell. The third helps improve protein function once everything is in place. It’s the combination of the efficiency of the drugs together that’s made TRIKAFTA such an effective CFTR modulator for this patient population.
Related reading: How CFTR modulators benefit cystic fibrosis patients
The challenges and triumphs of cystic fibrosis care
Raksha Jain, M.D., the Medical Director of the Adult Cystic Fibrosis Program at UT Southwestern, is at the forefront of improving treatments for cystic fibrosis patients, who are living longer and better lives.
Steps to get on the therapy
Today, only patients with one or more Phe508del mutations are eligible for TRIKAFTA. Due to a push in genetic testing in the last decade, we know which gene mutations most of our current patients have. For those we don't, we’re capturing that data so we can answer their questions about this and other therapies.
From there, we will discuss with the patient their medical history, symptoms, and whether TRIKAFTA is an option for them. We will also discuss how to take the drug, as well as its benefits and risks, including drug interactions and potential side effects.
While short-term data are promising, not all patients will experience the same response. As such, patients who take TRIKAFTA will require close observation from a cystic fibrosis specialist, as well as experts in organ systems affected by CF, including the digestive system, liver, and bones. UT Southwestern is currently involved in clinical studies to determine therapies and preventive strategies for patients who experience these disease complications. Learn more.
This is a complex drug that is only available at specialty pharmacies. Many patients today use mail-out pharmaceutical services – a process that can take a few weeks for each refill. Additionally, because it is such a new drug, getting TRIKAFTA approved through insurance or copay assistance programs requires navigational assistance.
Just 50 years ago, there were no real therapies available for people with CF. TRIKAFTA is a transformative medicine that has potential to change CF treatment as we know it. We have seen it improve patients' daily lives, a feat which is monumental for patients with cystic fibrosis. We anticipate that this new drug – along with the many therapies in development to manage other gene mutations – will improve patients' long-term survival and quality of life just as dramatically.
Any patient who is eligible or wants to determine their eligibility for TRIKAFTA is welcome to request an appointment with our CF team. To visit with an expert, call 214-645-8300 or request an appointment online.