Data published in The Lancet has shown that patients on Afinitor® (everolimus) tablets with non-cancerous kidney tumours known as renal angiomyolipomas associated with tuberous sclerosis complex (TSC) experienced a significant reduction in tumour size and the absence of tumour progression.
Additionally, a recent issue of The Lancet featured results from a separate everolimus trial demonstrating a reduction in the size of non-cancerous brain tumours known as subependymal giant cell astrocytomas (SEGAs) associated with TSC.
Affecting one to two million people worldwide, TSC is a genetic disorder that may cause non-cancerous tumours to form in vital organs, including the kidney and brain. Known as Votubia® in the European Union (EU) and Switzerland for the treatment of certain patients with TSC, everolimus is the first and only medication for adult patients with these kidney tumours associated with TSC who do not require immediate surgery, and separately for paediatric and adult patients with SEGAs who require therapeutic intervention but are not amenable to surgery.[4,5]
“The positive findings of these two trials published in The Lancet represent a significant advance for people living with TSC,” said Dr. John Bissler, lead EXIST-2 study author and Clark D. West Endowed Chair of Nephrology at Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. “Rare diseases such as TSC are often overlooked, making publication of these studies important to help further awareness among the medical community, as well as reinforcing the importance of monitoring individuals for this serious and difficult-to-treat condition.”
The Phase III EXIST-2 trial published in The Lancet reported that 42% of patients taking everolimus experienced an angiomyolipoma response versus 0% of patients in the placebo arm (p<0.0001). Everolimus also demonstrated superiority to placebo for both secondary endpoints assessed. Time to angiomyolipoma progression was statistically significantly longer in patients on everolimus versus placebo (p<0.0001). In patients with skin lesions, a key concern for those with TSC, a 26% response rate was seen with everolimus versus 0% with placebo (p=0.0002). Results from a separate Phase III trial of TSC patients called EXIST-1, also published in a recent issue of The Lancet, showed that 35% of patients with SEGAs associated with TSC treated with everolimus experienced a 50% or greater reduction in SEGA volume versus 0% of patients on placebo (p<0.0001).
Renal angiomyolipomas, or potentially life-threatening kidney tumours, occur in up to 80% of patients with TSC, with typical onset occurring between the ages of 15 and 30 and prevalence increasing with age. SEGAs occur in up to 20% of children and adults with TSC and may pose a significant medical risk, including the potential for swelling in the brain (hydrocephalus).
Everolimus works by inhibiting mTOR, a protein implicated in many tumour-causing pathways. TSC is caused by defects in the TSC1 and/or TSC2 genes. When these genes are defective, mTOR activity is increased and can cause uncontrolled tumour cell growth and proliferation, blood vessel growth and altered cellular metabolism.[6,7]
“Novartis has a long-standing commitment to meeting the needs of patients affected by rare diseases, such as TSC, with a focus on understanding the fundamental mechanisms of the underlying condition,” said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. “We strive to improve the lives of these patients with the goal of bringing the right treatment to the right patient across a broad range of diseases, based on patient need, not population size.”
Novartis is committed to supporting individuals affected by TSC through therapeutic innovation, patient assistance, disease education and support of advocacy organisations.
- Bissler J, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a multicentre, randomised, double-blind, placebo-controlled trial. The Lancet 2012: 380.
- Franz D, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. The Lancet 2012:1-8.
- National Institute of Neurological Disorders and Stroke. Tuberous Sclerosis Fact Sheet. Available at http://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm. Accessed January 2013.
- Votubia® (everolimus) tablets Summary of Product Characteristics. Basel, Switzerland: Novartis; January 2013.
- Afinitor US Prescribing Information. http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf. Accessed January 2013.
- Motzer, et al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer. 2010 Sep;116(18):4256-4265.
- Krueger D, et al. Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis. N Engl J Med. 2010 Nov;363(19):1801-11.