FDA Grants Olaparib Orphan Drug Designation for Pancreatic Cancer


The FDA has granted olaparib an orphan drug designation for the treatment of patients with pancreatic cancer.

Roy Baynes, MD, PhD

The FDA has granted olaparib (Lynparza) an orphan drug designation for the treatment of patients with pancreatic cancer, according to AstraZeneca and Merck, the developers of the PARP inhibitor.1

“The FDA granting orphan drug designation is a positive step for patients with pancreatic cancer and continues to reinforce the importance of our collaboration in bringing Lynparza to more patients in need,” said Roy Baynes, senior vice president and head of global clinical development, chief medical officer, at Merck Research Laboratories.

The companies announced a global strategic oncology collaboration to develop and commercialize olaparib, as well as the MEK inhibitor selumetinib, for multiple cancer types in July 2017.

Olaparib is being evaluated as maintenance therapy in the ongoing, randomized, multicenter, double-blind, placebo-controlled phase III POLO trial (NCT02184195), which is looking at patients with germline BRCA1/2-mutated metastatic pancreatic cancer whose disease has not progressed following first-line platinum-based chemotherapy.

A total 145 patients have been randomized 3:2 to receive oral olaparib tablets at 300 mg twice daily as maintenance therapy versus placebo also twice daily. Randomization occurs within 6 weeks following last chemotherapy dose and olaparib/placebo treatment will begin within 4 to 8 weeks of the last chemotherapy dose. Following randomization, patients have weekly clinical visits for the first 4 weeks of treatment, then every 4 weeks while on study treatment.

Treatment will continue until objective radiological disease progression. Following progression, patients will be followed for second progression every 8 weeks, and then for survival until final analysis.

Eligible patients were previously treated for metastatic disease and have not progressed following completion of at least 16 weeks of frontline platinum-based chemotherapy. Additionally, patients must have a known deleterious or suspected deleterious germline BRCA mutation. Those who were previously treated with a PARP inhibitor were excluded.

The primary endpoint is progression-free survival. Secondary endpoints are overall survival, time from randomization to second progression or death, objective response rate, disease control rate, safety, and tolerability. Results from this study are expected in the first half of 2019.

The FDA grants orphan drug designation status to medicines intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Pancreatic cancer accounts for approximately 3% of all U.S. cancers and 5-year survival rates remain at 8.5%, AstraZeneca stated in a news release.

“Pancreatic cancer is an area of significant unmet medical need,” said Sean Bohen, executive vice president, global medicines development, and chief medical officer at AstraZeneca. “This is especially true for patients with metastatic disease, where the benefits of current treatment options are very limited.”

This is the fourth tme the FDA has designated olaparib as an orphan drug, the first coming in 2013 for the treatment of patients with ovarian cancer. In August 2017, the FDA expanded approval of olaparib tablets as a maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy regardless of BRCA status based on data from the phase III SOLO2 and the phase II Study 19 trials. In 2018, the agency granted an amended orphan drug status to include both fallopian tube and primary peritoneal cancers.

In SOLO2, maintenance treatment with olaparib showed a 70% reduction in the risk of progression or death compared with placebo for patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer.2 In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of BRCA status.3


  1. AstraZeneca. US FDA grants Lynparza orphan drug designation for pancreatic cancer. Published October 16, 2018. https://bit.ly/2pYa7c8. Accessed October 16, 2018.
  2. Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial [published online July 25]. Lancet Oncol. doi: 10.1016/S1470-2045(17)30469-2.
  3. Gourley C, Friedlander M, Matalonis U, et al. Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol. 2017;35(suppl; abstr 5533).
Related Videos
John Michael Bryant, MD,
Jacob Shreve, MD, MS, hematology/oncology fellow, Mayo Clinic
Efrat Dotan, MD, Fox Chase Cancer Center
A panel of 4 experts on gastrointestinal cancers
A panel of 4 experts on gastrointestinal cancers
Zev A. Wainberg, MD
A panel of 4 experts on gastrointestinal cancers
A panel of 4 experts on gastrointestinal cancers
John Michael Bryant, MD,
A panel of 4 experts on gastrointestinal cancers