Groundbreaking Drug Launches
Deutivacaftor/tezacaftor/vanzacaftor (ALYFTREK)
Mechanism of Action: Cystic fibrosis transmembrane conductance regulator stimulants Drug class: Small molecules Originator: Vertex Pharmaceuticals Indication: Cystic fibrosis Approved: UK, USA, EU Trials: SKYLINE 102 and SKYLINE 103
Cystic fibrosis
Cystic fibrosis (CF) is a genetic condition passed down through families that causes damage to the lungs, digestive system, and other organs. CF affects the cells that produce mucus, sweat, and digestive fluids. In healthy individuals, these fluids are typically thin and slippery, helping to protect and smooth internal tubes and ducts. However, in people with CF, a genetic mutation causes these secretions to become thick and sticky. This buildup can block pathways, particularly in the lungs and pancreas. CF is a progressive condition that requires daily management, but people with CF are often able to attend school and work. Thanks to advancements in screening and treatment, individuals with CF today can live into their mid-50s or beyond, and some are diagnosed later in life. Overall, the quality of life for CF patients has improved significantly compared to past decades.
Prevalence
Cystic fibrosis (CF) occurs in approximately 1 in 3,000 to 4,000 live births among Caucasians. Around 1 in 25 to 30 Caucasians are carriers of a pathogenic mutation in the CFTR gene. In other racial and ethnic groups, CF is less common. It affects roughly 1 in 4,000 to 10,000 Latin Americans, 1 in 15,000 to 20,000 African Americans, and is even less prevalent among Asian Americans. CF is rare in Asian populations, with an estimated prevalence of 1 in 40,000 to 1 in 100,000 births in India and 1 in 100,000 to 1 in 350,000 in Japan. In the United States, around 1,000 new CF diagnoses are made each year.
Treatment challenges
Three key challenges have been identified as barriers to further improving outcomes in cystic fibrosis care: (1) the rising prevalence of hard-to-treat bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), (2) the increasing complexity of treatment regimens due to the introduction of multiple new therapies, which can lead to patient nonadherence, and (3) the need to address the underlying CFTR dysfunction to prevent the progression of lung disease. Additionally, some medications can cause serious side effects, including headaches, upper respiratory infections, abdominal pain, diarrhea, rashes, and elevated liver enzymes.
Why is Deutivacaftor/tezacaftor/vanzacaftor poised to make an impact in 2025?
Vertex Pharmaceuticals has announced that the US FDA and Medicines and Healthcare products Regulatory Agency (MHRA) have approved its new cystic fibrosis treatment, Alyftrek, a combination therapy designed to improve on Trikafta. Trikafta generated $8.9 billion in sales in 2023. This news is a welcome relief for Vertex following the disappointing clinical results for its non-opioid analgesic.
William Blair analysts consider the early approval of Alyftrek a favorable development for the company’s stock. However, the stock has not yet recovered from the significant drop following the release of Phase II trial results for the painkiller, which caused shares to fall more than 10%, and the stock remains at a depressed level.
Like Trikafta, Alyftrek is a triple-combination therapy intended for individuals with at least one F508del mutation or another CFTR gene mutation that responds to the treatment. However, the two therapies share only one active ingredient, and Vertex emphasizes that the combination of drugs in Alyftrek offers benefits over Trikafta.
“Alyftrek is expected to boost the company's stock following its future launch”
Regulatory milestones
Registrational Trials
The U.S. Food and Drug Administration (FDA) has approved ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), for the treatment of cystic fibrosis (CF) in people 6 years and older who have at least one F508del mutation or another mutation in the CFTR gene that is responsive to Deutivacaftor/tezacaftor/vanzacaftor (ALYFTREK) based on results of SKYLINE 102 and SKYLINE 103 trials.
SKYLINE 102:
A phase 3 clinical trial aimed to evaluate the efficacy and safety of Deutivacaftor/tezacaftor/vanzacaftor (Alyftrek), a once-daily oral combination therapy, in individuals aged 12 years and older with cystic fibrosis who are heterozygous for the F508del mutation and a minimal function mutation (NCT05033080).
SKYLINE 103:
A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive CFTR Mutation and No F508del Mutation (NCT05076149).
“Alyftrek improved lung function like Trikafta and reduced sweat chloride levels more than Trikafta”