FDA Approves Generic Everolimus Tablets

In Clinical Studies News by Barbara Jacoby

By: Kristi Rosa

From: onclive.com

The FDA has approved 2 abbreviated new drug applications (ANDAs) for everolimus (Afinitor) tablets for the treatment of patients with advanced hormone receptor–positive, HER2-negative breast cancer in postmenopausal women; advanced renal cell carcinoma; progressive neuroendocrine tumors (NETs) of pancreatic origin; and progressive, well-differentiated, non-functional NETs of gastrointestinal or lung origin that are unresectable; and renal angiomyolipoma and tuberous sclerosis complex.

The applications were submitted by Teva Pharmaceuticals and Par Pharmaceuticals. In Teva’s application, the generic tablets are approved at 2.5 mg, 5 mg, 7.5 mg, and 10 mg doses; Par Pharmaceutical’s application is for 2.5 mg, 5 mg, 7.5 mg doses of the tablet.

“We are pleased to bring the first generic Afinitor to market and provide patients with a lower-cost option,” Domenic Ciarico, executive vice president and chief commercial officer, Sterile & Generics at Endo International plc, which operates Par, stated in a press release. “This launch is a testament to Par’s expertise in manufacturing technically challenging products while maintaining excellence in quality.”

In the United States, 9 out of 10 prescriptions that are filled are for generic drugs. The FDA’s Office of Generic Drugs follows a rigorous review process to ensure that proposed generic medication contain the same key ingredient, possesses the same efficacy, use the same dosage from and route of administration as the brand-name medications.

Everolimus received regulatory approval for patients with advanced RCC after failure on sunitinib (Sutent) or sorafenib (Nexavar) in March 2009. Two years later, in May 2011, the agent became the first new treatment approved for use in patients with advanced pancreatic NETS in nearly 3 decades, based on data from the phase III RADIANT-3 trial. Specifically, everolimus more than doubled the time without tumor growth (median 4.6-11.0 months) and reduced the risk of cancer progression by 65% versus placebo in this patient population (HR, 0.35; 95% CI, 0.27-0.45; P <.001), according to data from the phase III RADIANT-3 trial.3

Notably, everolimus was the first of its class of mTOR inhibitors to receive approval in July 2012 for the treatment of postmenopausal women with advanced HR-positive breast cancer. The decision was based on data from an interim analysis of the phase III BOLERO-2 trial, which showed that everolimus in combination with exemestane led to a progression-free survival (PFS) of 6.9 months versus just 2.8 months with exemestane alone (HR, 0.43; 95% CI, 0.35-0.54; P <.001).4

Although the drug had received prior approvals in RCC, pancreatic NETs, and subependymal giant cell astrocytoma, a type of brain tumor associated with tuberous sclerosis, this was its first indication for breast cancer.

Most recently, in February 2016, the agent was approved for use in the treatment of adult patients with progressive, well-differentiated non-functional, locally advanced or metastatic gastrointestinal or lung NETs, following findings from the phase III RADIANT-4 trial. In the trial, median PFS was 11 months with everolimus compared with 3.9 months with placebo, translating to a 52% reduction in the risk of progression or death (HR, 0.48; 95% CI, 0.35-0.67; P <.001).5

The generic product is available for immediate shipping, according to Endo International plc. Sales for the brand-name medication in 2.5 mg, 5 mg, and 7.5 mg doses were approximately $412 million over the last 4 quarters, according to IQVIA data.6


  1. US Food and Drug Administration. First generic drug approvals. fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals. Accessed December 10, 2019.
  2. US Food and Drug Administration. Generic drugs: overview & basics. fda.gov/drugs/generic-drugs/overview-basics. Accessed December 10, 2019.
  3. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514-523. doi: 10.1056/NEJMoa1009290.
  4. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520-529. doi: 10.1056/NEJMoa1109653.
  5. Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968-977. doi: 10.1016/S0140-6736(15)00817-X.
  6. Endo launches generic version of Afinitor (everolimus) tablets in the United States [news release]. Dublic, Ireland: Endo International plc; December 10, 2019. prn.to/36odf4k. Accessed December 10, 2019.