Data published today in The Lancet showed that patients on Afinitor (everolimus) tablets with non-cancerous kidney tumors known as renal angiomyolipomas associated with tuberous sclerosis complex (TSC) experienced a significant reduction in tumor size and the absence of tumor 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 tumors known as subependymal giant cell astrocytomas (SEGAs) associated with TSC2.
Affecting one to two million people worldwide, TSC is a genetic disorder that may cause non-cancerous tumors to form in vital organs, including the kidney and brain3. Known as VotubiaÂ® 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 tumors associated with TSC who do not require immediate surgery, and separately for pediatric and adult patients with SEGAs who require therapeutic intervention but cannot be curatively resected.
"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)1. 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 tumors, occur in up to 80% of patients with TSC, with typical onset occurring between the ages of 15 and 30 and prevalence increasing with age3. 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 tumor-causing pathways6. TSC is caused by defects in the TSC1 and/or TSC2 genes3. When these genes are defective, mTOR activity is increased and can cause uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism.
"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 DevelopmentÂ & 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 Pharmaceuticals Corporation is committed to supporting individuals affected by TSC through therapeutic innovation, patient assistance, disease education and support of advocacy organizations.