A majority of cystic fibrosis patients who took part in an Instagram poll by BioNews Services said they would be interested in moving from current treatments to Trikafta (elexacaftor, tezacaftor, and ivacaftor), the newly approved and “next-generation” combination therapy by Vertex that is expected to treat 90% of all with CF.
“My doctor told me that the new med blows Symdeko out of the water!” said Christina Khoury of Pennsylvania, who was diagnosed at 3 weeks old.
Others, including Wendy Caroline of Wisconsin and Elizabeth Rogers of California, both diagnosed before age 2, simply noted that Orkambi and Symdeko hadn’t work as hoped, and were a “disappointment.”
Drew Hanley of Florida, diagnosed at 13, was a bit more succinct: “In medical lingo — Symdeko and Orkambi were never considered highly effective. Trikafta is.”
The informal, one-day poll, conducted Oct. 22–23, asked seven questions largely to patients who follow Cystic Fibrosis News Today (a BioNews publication).
It also found that most were not surprised by the U.S. Food and Drug Administration’s quick approval — a little more thab two months since a request for approval was filed and given an accelerated review. Perhaps that is because of the positive results reported from clinical trials.
A slight majority, 54% of the 212 people who responded to this question, thought the FDA’s speedy review was reasonable.
But a stronger majority — 83% of 193 people responding — were disappointed in Trikafta’s expected $311,500 yearly list price in the U.S., equivalent to $23,896 for a 28-day supply, according to financial reports. That puts Trikafta’s list price up with Kalydeco (ivacaftor), Vertex’s most effective CF therapy to date, but a potentiator that treats only about 6% of all patients, as the most expensive of all of the company’s CF medications.
Symdeko carries a yearly list price of about $292,000, and Orkambi of about $272,000. Financial analysts in the U.S. had speculated that Trikafta would enter the market at a list price similar to Symdeko. That it appears unlikely to do so has some patients worried.
“FOR SURE,” said respondent Bethany Schulberg of the United States, diagnosed at 18 months.”The cost of this will make it difficult for people who have certain insurance access.”
Insurance coverage and its quality could be key.
Caroline of Wisconsin, diagnosed at 6 weeks old, considered herself fortunate: “I’m lucky to have good insurance, so it shouldn’t be an issue for me personally.”
Keisha Hummel, also of the U.S., said she’s a “[h]ighly concerned adult with CF & married. Insurance is always a big issue for me. Always fighting.”
Those from other countries expected a long wait, calling Trikafta’s likely arrival at their home a “dream.” (Respondents who could not be reached later to confirm use of their statements are not quoted.)
Trikafta, whose U.S. approval was based on two Phase 3 clinical trials in the AURORA program, is expected to be available soon for patients ages 12 and older with one F508del and one minimal function mutation in the CFTR gene, or with two F508del mutations, reflecting the patient groups evaluated in each trial — NCT03525444 for one F508del mutation, and NCT03525548 for two.
An F508del defect in CFTR gene — the most common CF mutation — leads to faulty instructions being given for the creation of the CFTR protein. This protein regulates the production of mucus needed to lubricate organs, especially the lungs and digestive system, by controlling the transport of charged substances (chloride and sodium, especially) across cell membranes. Its failure results in a buildup of thick mucus that is difficult to clear and traps viruses and bacteria, promoting infections that weaken patients and damage their organs.
Previously approved Vertex therapies — Kalydeco, Orkambi, and Symdeko — were able to treat some people with one or two F508del mutations in CFTR, but not those with what are called “minimal function” or “nonsense” mutations. More than 1,700 mutations are known to exist in the CFTR gene, and nonsense mutations are those that prematurely stop the CFTR protein from forming.
Because this triple combination covers people with both the common F508del mutation and those with another minimal function mutation, it is expected to treat up to 90% of all CF.
Data from both AURORA studies showed significant gains in lung health in people on Trikafta, the primary goal of each trial, as assessed by the percent predicted forced expiratory volume in one second (ppFEV1, a widely used measure of lung function). ppFEV1 increased by an average of 13.8 percentage points in AURORA F/MF, which enrolled people with one F508del and one nonsense mutation, and by 10 percentage points in AURORA F/F, in which patients had two F508del mutations.
Trikafta-treated patients in AURORA F/MF also showed improvements in all secondary study goals, including a lower annual rate of pulmonary flares and diminished sweat chloride levels.
“Today’s landmark approval is a testament to … making a novel treatment available to most cystic fibrosis patients, including adolescents, who previously had no options, and giving others in the cystic fibrosis community access to an additional effective therapy,” Ned Sharpless, MD, the FDA’s acting commissioner, said in an agency release announcing Trikafta’s Oct. 21 approval.
The importance of this “new option” is evident: In this one-day poll on Instagram, where responses were limited by the nature of this social media platform, 47% of the 165 respondents — a near majority — said Trikafta would be a first CF treatment available to them.
Curiously, a follow-up question — asking how they felt about having a first disease-modifying treatment — was the only question to elicit no response.