September 2020 • PharmaTimes Magazine • 8-9
// MEDICINE //
Vertex Pharmaceuticals' Kaftrio (ivacaftor/tezacaftor/elexacaftor) has been approved by the European Commission for use in combination with ivacaftor to treat people aged 12 years and older with certain forms of cystic fibrosis.
Specifically, the decision allows doctors to prescribe the drug when people with the disease are carrying one F508del mutation and one minimal function mutation (F/MF), or two F508del mutations (F/F) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
It means that, for the first time, up to 10,000 people in Europe ages 12 years and older with CF and these mutations will be eligible for a CFTR modulator that treats the underlying cause of the disease.
Approval of the triple combination regimen also expands the number of treatment options available to people ages 12 years and older with CF who have two copies of the F508del mutation, the most common CF-causing mutation worldwide, the firm noted.
Clearance was based on data from two global Phase III studies, which showed statistically significant and clinically meaningful improvements in lung function (primary endpoint) and all key secondary endpoints.
“The triple combination regimen has been shown to have a major impact on several outcome measures in people with CF,” said Professor Harry Heijerman, Professor and head of the Department of Pulmonology at University Medical Center Utrecht, Netherlands. “The clinical data showed significant improvements in lung function and other important measures, such as sweat chloride levels and quality of life as measured by the CFQ-R respiratory domain score, in patients treated with the triple combination therapy.”
David Ramsden, chief executive of the Cystic Fibrosis Trust, said the approval “marks a step change in the treatment of cystic fibrosis”, adding: “It’s also great news that more mutations have been added to those eligible for Kalydeco and Symkevi, giving more children and adults with CF a disease-modifying treatment option.”
Long-term reimbursement agreements for the triple combination have already been secured in the UK, meaning that eligible patients will have access to the treatment in the coming weeks.
The National Institute for Health and Care Excellence (NICE) has recommended NHS use of Merck and Pfizer's immunotherapy Bavencio (avelumab) in combination with tyrosine kinase inhibitor axitinib as a first-line treatment for kidney cancer.
Specifically, use of the therapy will be funded via the Cancer Drugs Fund (CDF) when used for the first-line treatment of adult NHS patients with advanced renal cell carcinoma (RCC).
The firms highlight that advanced RCC outcomes remain “unacceptably poor”, with a five-year survival rate of around 12% at the latest stage, underscoring the urgent need for more first-line treatment options.
In the JAVELIN Renal 101 study, the Bavencio/axitinib combination significantly lowered the risk of disease progression or death by 31%, irrespective of PD-L1 status, compared to sunitinib, while median progression free survival was improved by 5.3 months. The study is ongoing to determine overall survival benefit.
“This positive recommendation from NICE provides patients with advanced renal cancer an effective and well tolerated treatment option with proven benefits in progression free survival and objective response rates from a randomised Phase III trial,” said Professor Amit Bahl, a consultant medical oncologist specialising in renal cell carcinoma. “This could improve outcomes in this group of patients. The combination of an immunotherapy with a tyrosine kinase inhibitor provides patients a novel treatment option.”
BioMarin has submitted a marketing application to the European Medicines Agency (EMA) for vosoritide, an investigational, once daily injection analogue of C-type Natriuretic Peptide (CNP) for children with achondroplasia, the most common form of disproportionate short stature in humans.
Achondroplasia is characterised by slowing of endochondral ossification, which results in disproportionate short stature and 'disordered architecture' in the long bones, spine, face and base of the skull.
People with achondroplasia can also experience serious health complications, including foramen magnum compression, sleep apnoea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis and recurrent ear infections.
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Vosoritide, derived from a natural human peptide positively regulates bone growth, binds to a specific receptor which initiates intracellular signals that inhibit the overactive FGFR3 pathway.
If approved, vosoritide would be the first medicine for the treatment of achondroplasia in Europe.
“Years of scientific research have led to this important point in the development of the potentially first pharmacological treatment option for children with achondroplasia,” said Hank Fuchs, president Worldwide Research and Development at BioMarin.
“We have worked alongside patient advocacy groups from around the world throughout the development, and we appreciate the implications of developing a treatment option for this community, recognising that this potential new treatment would offer a choice for families who have a child with achondroplasia.”