Source: Thailand Medical News Nov 02, 2019 5 years, 1 month, 3 weeks, 8 hours ago
Clinical researchers from the University Of Texas Southwestern Medical Center have demonstrated through a phase three clinical trial that a three-drug combination improved lung function and reduced symptoms in
cystic fibrosis (CF) patients who have a single copy of the most common genetic mutation for the disease.
The US FDA has also approved the therapy based on the results of this international study.
Cystic Fibrosis is a chronic, progressive, and frequently fatal genetic disease that affects the respiratory and digestive systems in children and young adults. The sweat gland and the reproductive system are also usually involved. Individuals with CF have a shortened lifespan.
Dr. Raksha Jain, Associate Professor of Internal Medicine at UT Southwestern Medical Center commented in an interview with
Thailand Medical News, "Although there are over a thousand different disease-causing mutations, nearly 90 percent of people with
cystic fibrosis have at least one copy of the most common mutation, the Phe508del CFTR allele.”
It is estimated that about 80,000 people worldwide are affected by mutations in the
cystic fibrosis transmembrane conductance regulator (CFTR) protein. People inherit a gene from each parent that encodes the CFTR protein.
Dr. Raksha Jain further commented, "This three-drug combination was highly effective in people with
cystic fibrosis who inherited the Phe508del CFTR mutation, improving health outcomes and symptoms."
In the international clinical trial conducted at 115 sites in 13 countries from June 2018 to April 2019, 403 patients of ages 12 and older were randomized to receive either elexacaftor-tezacaftor-ivacaftor combined therapy or a placebo. The trial was co-sponsored by Vertex Pharmaceuticals.
Pulmonary function was measured at four and 24 weeks. Compared with patients receiving a placebo, lung function in the treatment group was significantly improved at four weeks and sustained through week 24. In addition, lung flare-ups, or increases in symptoms, were 63 percent lower in the treatment group. Study participants also answered questionnaires regarding their quality of life and respiratory symptoms with those in the treatment group reporting higher scores in these areas.
Typically excessive amounts of salt via sweating is a hallmark of
cystic fibrosis. The treatment group had a lower concentration of salt in their sweat than the placebo group, which demonstrates how this therapy in targeting the underlying cause of the disease.
Only less than 1 percent experienced adverse events taking the drug combo that led to discontinuation. Although the therapy was generally safe and well-tolerated, long-term studies are needed to further understand potential side effects.
Dr. Jain, a Dedman Family Scholar in Clinical Care and Director of the UTSW
Adult Cystic Fibrosis Center further commented, "The
CF community is working hard to find highly effective therapies for people who are not eligible for this treatment because they don't have the appropriate gene mutation,"
The study was published in the
New England Journal of Medicine. A companion investigation appearing simultaneously in The Lancet reported on people with one or two copies of the mutation. Dr. Raksha Jain, Associate Professor of Internal Medicine at University of Texas Southwestern Medical Center, is corresponding author of the
NEJM article and an investigator on The Lancet study.
Reference: Peter G. Middleton et al, Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele, New England Journal of Medicine (2019). DOI: 10.1056/NEJMoa1908639
