As Vertex Pharmaceuticals reels from a painful trial readout for its pain candidate suzetrigine, the Boston biotech has chalked up a win in its specialty area of cystic fibrosis.
The FDA has approved Vertex’s Alyftrek, a once-daily triple combination for the treatment of cystic fibrosis in people 6 years and older who have mutations that are amenable to the therapy, the company said Friday.
Alyftrek combines vanzacaftor, tezacaftor and deutivacaftor and is the fifth cystic fibrosis transmembrane conductance regulator (CFTR) modulator from Vertex.
The FDA approval covers patients who have at least one F508del mutation or another mutation in the CFTR gene that’s responsive to Alyftrek. In patients with CF, mutations in the CFTR gene disrupt the function or amount of the CFTR protein channel at the cell surface, causing progressive damage to multiple organs, including the lungs, eventually leading to death.
Compared with Vertex’s mainstay CF therapy, twice-daily Trikafta (elexacaftor/tezacaftor/ivacaftor), Alyftrek is given once a day and has efficacy in 31 additional mutations, Vertex CEO Reshma Kewalramani, M.D., noted in a statement Friday.
By Vertex’s estimate, Alyftrek’s wider mutation coverage means that about 150 people with CF in the U.S. are now eligible for a CFTR modulator for the first time.
In two phase 3 trials conducted in CF patients ages 12 years and older, Alyftrek matched Trikafta in patients’ change in lung function. For their primary endpoints, the trials measured the volume of air participants could forcefully exhale in one second (ppFEV1) through 24 weeks. Alyftrek was better than Trikafta in reducing sweat chloride, a key secondary endpoint of both studies.
The new triplet’s efficacy in patients ages 6 to 11 years was extrapolated from the above two studies with support from pharmacokinetic analyses. A third phase 3 trial established the safety of Alyftrek in those younger patients.
Similar to Trikafta, Alyftrek’s label includes a black box warning detailing the risk of liver toxicities. This warning requires annual liver function monitoring and more frequent tests during the first year of treatment.
Vertex has priced Alyftrek at a list price of $370,269 per year, which is 7% higher than Trikafta’s annual wholesale acquisition cost of $346,048, according to a securities filing.
More convenient once-daily dosing and either noninferior or better clinical data compared with Trikafta will make converting patients to Alyftrek “fairly straightforward,” Leerink Partners analysts said in a note Sunday.
Early adopters of Alyftrek will likely include patients who are experiencing insufficient efficacy, poor compliance or tolerability issues with Trikafta, Evercore ISI analysts said in a Friday note. About 20% to 30% of current Trikafta takers struggle with those difficulties, according to Evercore’s estimate.
However, William Blair analysts argued that the Alyftrek was less disruptive to the CF treatment landscape than Trikafta was when it entered the market in 2019 as the first triple combination for CF with superior efficacy than Vertex’s earlier offerings.
Therefore, William Blair predicted that Alyftrek’s penetration into the estimated 20,000 patients worldwide who are not currently on a CFTR modulator—and the switch over from Trikafta—will be slower than Trikafta’s launch. Nevertheless, the analysts suggested that Vertex will successfully switch patients “over the long term.”
Vertex became a Big Biotech company thanks to its CF franchise, which is now tracking toward more than $10 billion in annual sales. Trikafta—known as Kaftrio in Europe—itself has contributed $7.5 billion during the first nine months of 2024.
But investors’ attention has lately shifted to suzetrigine, a nonaddictive pain candidate sitting on the verge of a potential FDA approval in January 2025 for the treatment of acute pain. As an alternative to opioids, the drug bears blockbuster expectations.
However, results from a phase 2 trial in painful lumbosacral radiculopathy last week spooked investors, as suzetrigine performed similarly to placebo even though the trial was not designed to make that comparison. Vertex’s share price plunged more than 10% after the readout and has not recovered since despite Alyftrek’s FDA approval.