The U.S. Food and Drug Administration has approved generic everolimus tablets for oral suspension (2 mg, 3 mg, and 5 mg) for treating subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC). The approval, granted to Breckenridge Pharmaceutical Inc., covers both adult and pediatric patients aged 1 year and older whose tumors cannot be surgically removed and require therapeutic intervention.
Understanding Tuberous Sclerosis Complex
TSC is a rare genetic disorder characterized by the growth of benign tumors throughout the body, including the brain, spinal cord, nerves, eyes, lungs, heart, kidneys, and skin. While there is currently no cure for this lifelong condition, various treatments are available to manage its diverse symptoms, which include seizures, cognitive difficulties, behavioral challenges, and autism spectrum disorder.
Clinical Evidence Supporting Approval
The approval is supported by data from the EXIST-1 trial (NCT00789828), a randomized, double-blind, placebo-controlled phase 3 study. The trial enrolled 117 patients, who were randomized in a 2:1 ratio to receive either everolimus (n=78) or placebo (n=39). Patients in the treatment group received 4.5 mg/m² daily, with doses adjusted to maintain blood trough concentrations between 5-15 ng/mL.
The results were striking: 35% of patients receiving everolimus achieved a 50% or greater reduction in SEGA volume, while no patients in the placebo group reached this milestone (difference 35%, 95% CI 15-52; P<.0001).
Safety Profile and Treatment Considerations
The drug demonstrated a manageable safety profile, with most adverse events being grade 1 or 2 in severity. The most commonly reported side effects included:
- Mouth ulceration (32%)
- Stomatitis (31%)
- Convulsion (23%)
- Pyrexia (22%)
Market Impact and Patient Access
This generic approval represents a significant advancement in making effective TSC treatments more accessible to patients. As an oral kinase inhibitor, everolimus has already proven its worth in the TSC treatment landscape, having received FDA approval in 2018 for TSC-associated partial-onset seizures in patients aged 2 years and older.
The availability of a generic version is expected to reduce treatment costs while maintaining the same therapeutic benefits as the brand-name version, Afinitor Disperz. This development is particularly important for patients with rare diseases like TSC, where treatment options are often limited and expensive.
