FDA Approves Symdeko (tezacaftor/ivacaftor and ivacaftor) to Treat the Underlying Cause of CF in Children Ages 6-11 Years with Certain Mutations in the CFTR Gene

In continuation of my update on tezacafto

   Tezacaftor 

                                            

                                                                                             Lumacaftor/ivacaftor

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX)  announced the U.S. Food and Drug Administration (FDA) approved Symdeko (tezacaftor/ivacaftor and ivacaftor) for use in children with cystic fibrosis ages 6 through 11 years who have two copies of the F508del-CFTR mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeko. It was previously approved by the FDA for use in patients with cystic fibrosis 12 years and older with two copies of the F508del mutation or one copy of a responsive mutation in the U.S. An additional dosage strength of Symdeko tablets is now available (tezacaftor 50 mg/ivacaftor 75 mg and ivacaftor 75 mg) in connection with this approval.

“Today’s expanded approval of Symdeko in children ages 6 through 11 is an important step in our efforts to continue to bring treatment options to the youngest patients possible and importantly brings us closer to our goal of developing medicines for all people living with CF,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex.

Vertex completed a 24-week Phase 3 open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of tezacaftor/ivacaftor and ivacaftor in children ages 6 through 11 years in the U.S. and Canada. The regimen was generally well tolerated, and safety data were similar to what was observed in previous studies of patients aged 12 years and older. The full data from this study will be published later this year.

“We’ve seen the clinical impact of Symdeko in people with CF aged 12 years and above, and this approval marks a crucial milestone for patients ages 6 through 11 years who may benefit from CFTR modulation, enabling us to treat the basic defect in CF at an earlier stage of disease,” said Seth Walker, M.D., University Hospitals of Cleveland, Cleveland Medical Center, Rainbow Babies and Children’s Hospital. “Symdeko is an important treatment option for eligible people with CF who either never started or have discontinued another CFTR modulator.”

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.

About Symdeko (tezacaftor/ivacaftor and ivacaftor) 

Some mutations result in CFTR protein that is not processed or folded normally within the cell, and that generally does not reach the cell surface. Symdeko is a combination of tezacaftor and ivacaftor. Tezacaftor is designed to address the trafficking and processing defect of the CFTR protein to enable it to reach the cell surface where ivacaftor can increase the amount of time the protein stays open.

U.S. INDICATION FOR SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) tablets 

Symdeko is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have two copies of the F508del mutation, or who have at least one mutation in the CF gene that is responsive to treatment with Symdeko. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if Symdeko is safe and effective in children under 6 years of age.

https://en.wikipedia.org/wiki/Tezacaftor

https://en.wikipedia.org/wiki/Lumacaftor/ivacaftor

FDA Approves Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for Cystic Fibrosis Patients Ages 12 and Older Who Have at Least One F508del Mutation

In continuation of my update on  tezacaftor  and ivacaftor

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the U.S. Food and Drug Administration (FDA) has approved Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for the treatment of cystic fibrosis (CF) in people ages 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the most common CF-causing mutation. With this approval, for the first time, approximately 6,000 people with CF ages 12 years and older who have one F508del mutation and one minimal function mutation (F/MF) have a medicine that targets the underlying cause of their CF. Additionally, approximately 12,000 people with one or two F508del mutations who are currently eligible for one of Vertex’s three other FDA-approved CF medicines are now also eligible for Trikafta.

“Today marks a milestone for CF patients, their families and Vertex. After a 20-year journey together, we have received FDA approval of Trikafta: a single breakthrough medicine with the potential to treat up to 90% of all people with CF in the future. For approximately 6,000 people with CF in the U.S., Trikafta is the first medicine that can treat the underlying cause of their disease,” said Jeffrey Leiden, M.D., Ph.D., Vertex's Chairman, President and Chief Executive Officer. “I want to personally thank the hundreds of Vertex scientists who have been working on this program for nearly 20 years – many of whom have dedicated their entire careers to changing the course of this disease; the CF Foundation which has provided support, encouragement and help throughout the journey; and most importantly the thousands of patients, caregivers, doctors and advocates who have courageously and persistently worked side-by-side with us to get to where we are today.”

“Today’s approval is a historic moment in cystic fibrosis care, with the potential for more people to benefit from CFTR modulator therapy to treat the basic defect of their disease,” said Steven Rowe, M.D., Director, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham. “In clinical trials, Trikafta was generally well tolerated and demonstrated improvements in multiple outcome measures in CF, including improvements in FEV1, improvements in respiratory symptoms and, in the 24-week F/MF study, a reduced rate of pulmonary exacerbations and improvements in BMI.”

“The incredible speed of this approval underscores our shared sense of urgency with the FDA and the CF community for bringing this medicine to eligible people with CF, particularly those without a medicine targeting the underlying cause of their disease,” said Reshma Kewalramani, M.D., Executive Vice President, Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex. “We remain committed to relentlessly pursuing the development of transformative therapies for all people living with this disease.”

Vertex has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the elexacaftor/tezacaftor/ivacaftor combination regimen. Vertex is currently evaluating elexacaftor/tezacaftor/ivacaftor in people ages 6 through 11 with F/MF and F/F CF mutations in an ongoing Phase 3 study and is committed to evaluating elexacaftor/tezacaftor/ivacaftor in children <6 years of age as part of planned future studies.

     

https://en.wikipedia.org/wiki/Elexacaftor/ivacaftor/tezacaftor

https://en.wikipedia.org/wiki/Ivacaftor

https://en.wikipedia.org/wiki/Elexacaftor/ivacaftor/tezacaftor

FDA Approves Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for Cystic Fibrosis Patients Ages 12 and Older Who Have at Least One F508del Mutation

FDA Approves Symdeko (tezacaftor/ivacaftor and ivacaftor) to Treat Cystic Fibrosis in People Ages 12 and Older with Certain Mutations in the CFTR Gene

Vertex Pharmaceuticals Incorporated announced  the U.S. Food and Drug Administration (FDA) approval of  Symdeko (tezacaftor/ivacaftor and ivacaftor) for treating the underlying cause of cystic fibrosis (CF) in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor. Symdeko is Vertex's third medicine approved to treat the underlying cause of CF. Vertex is ready to launch Symdeko and will begin shipping it to pharmacies in the United States this week.

Ivacaftotezacaftor

"Today is an exciting day for the CF community. The approval of Symdeko, our third disease-modifying CF medicine, offers many patients an important new treatment option," said Jeffrey Leiden, M.D., Ph.D., Vertex's Chairman, President and Chief Executive Officer. "This approval is an important milestone in our journey to treat every person with CF, and we remain committed to urgently advancing our efforts to develop new medicines that treat the underlying cause of CF for the many people still waiting."

In November 2017, the New England Journal of Medicine published the results of two Phase 3 studies of Symdeko. These studies, named EVOLVE and EXPAND, enrolled approximately 750 people with CF ages 12 and older with two copies of the F508del mutation or with one F508del mutation and one mutation that results in residual CFTR function. Across both studies, patients treated with Symdeko experienced statistically significant and clinically meaningful improvements in lung function and other measures of disease, with a favorable safety profile. The most common adverse events, regardless of treatment group, included infective pulmonary exacerbation and cough. The first data from the ongoing EXTEND rollover study, also presented in November, show that the lung function improvements and the safety and tolerability profiles seen in EVOLVE and EXPAND were sustained for up to 48 total weeks of Symdeko treatment.

"We've already seen the significant impact that disease-modifying medicines can have on patients and are incredibly pleased that there is now a third treatment option that enables more patients to benefit from CFTR modulation," said Patrick Flume, M.D., Director of the Medical University of South Carolina Cystic Fibrosis Center and Principal Investigator for the EXTEND study. "In particular, Symdeko is an important treatment option for patients who either never started or discontinued Orkambi, and it also provides increased benefit over Kalydeco alone for patients with residual function mutations."

The European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for the tezacaftor/ivacaftor combination. The company expects approval in the EU in the second half of 2018.

FDA Approves Symdeko (tezacaftor/ivacaftor and ivacaftor) to Treat Cystic Fibrosis in People Ages 12 and Older with Certain Mutations in the CFTR Gene