February 22, 2019 Press Release

Imbrium Therapeutics Announces U.S. FDA Orphan Drug Designation for Etoposide Toniribate for the Treatment of Relapsed Refractory Biliary Tract Cancer

STAMFORD, Conn. – February 22, 2019 – Imbrium Therapeutics L.P., a clinical-stage biopharmaceutical company and operating subsidiary of Purdue Pharma L.P., in conjunction with Mundipharma EDO GmbH, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to its investigational drug etoposide toniribate, a novel topoisomerase II inhibitor, for the treatment of relapsed refractory biliary tract cancer.

Also known as cholangiocarcinoma, biliary tract cancer is a rare type of cancer that starts in the bile ducts, a series of thin tubes that move bile from the liver and gallbladder to the small intestine (duodenum) to help digest the fats in food. Biliary tract cancer is the second most common primary hepatobiliary cancer, after hepatocellular cancer. About 8,000 people in the United States are diagnosed with biliary tract cancer each year.1 It most commonly affects people age 65 or older.

“We are pleased that the FDA has granted orphan drug designation for etoposide toniribate as we believe, once approved, it can be an important clinical advance for patients suffering from relapsed refractory biliary tract cancer, a patient population that has limited treatment options,” said Paul Medeiros, president of Imbrium Therapeutics. “This designation represents Imbrium’s first milestone in oncology and underscores our commitment to advance the clinical development of oncology chemotherapeutics while actively collaborating to advance treatments across our therapeutic portfolio.”

The FDA, through its Office of Orphan Products Development (OOPD), grants orphan drug designation to drugs and biological products that are intended for the treatment of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug designation is intended to facilitate drug development for rare diseases and may provide certain incentives to drug developers, including seven years of market exclusivity and tax credits for qualified clinical testing.2,3

“While patients with early and locally advanced biliary tract cancer often can be treated successfully with surgery and chemotherapy, no treatments are approved for patients with relapsed or refractory disease who require second-line therapy, and only a few agents are in development,” said Craig Landau, MD, president and CEO, Purdue Pharma L.P. “This designation is another step toward the goal of advancing clinical development of etoposide toniribate, in conjunction with Mundipharma EDO, toward potential regulatory approval by the US FDA.”

Thomas Mehrling, MD, PhD, CEO of Mundipharma EDO, added, “We are pleased that the FDA has granted orphan drug designation to etoposide toniribate for relapsed refractory biliary tract cancer. As a company, we are focused on developing treatments for rare and difficult-to-treat cancers and getting them to patients as rapidly as possible. We look forward to accelerating the development of etoposide toniribate in conjunction with Imbrium Therapeutics.”

Etoposide toniribate has shown encouraging data in Phase 2 trials, and these data were key in securing the ODD.4The European Medicines Agency (EMA) granted orphan designation to etoposide toniribate on June 4, 2014.5

Imbrium Therapeutics, in collaboration with Mundipharma EDO GmbH, expects to initiate a Phase 3 clinical trial of etoposide toniribate in patients with refractory biliary tract cancer in 2020.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.

About Biliary Tract Cancer

Biliary tract cancer can develop in any part of the bile duct system. Among those with distal disease, the five-year survival is 15 percent, and the prognosis is worse for patients with intra-hepatic cancer compared with those with extra-hepatic cancer. Nearly two of three people with biliary tract cancer are age 65 or older at the time of diagnosis, and the average age is 70. Risk factors for biliary tract cancer include advancing age, diabetes, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), bile duct stones, cirrhosis, obesity, alcohol consumption, long-term infection with hepatitis B or C virus, and a family history of cholangiocarcinoma. Surgery and chemotherapy are commonly used for early and locally advanced disease, but no treatments are indicated as second-line therapy. Clinical trials of targeted agents and immunotherapy are underway.6

About Etoposide Toniribate

Etoposide toniribate is a novel chemotherapy agent of the topoisomerase II inhibitor class in clinical development for the treatment of relapsed refractory biliary tract cancer. This small molecule drug is designed to work by metabolizing into its active form through enzymes in the gastrointestinal tract that are particularly active in cancer cells. Activated etoposide binds to and inhibits topoisomerase II, which is often elevated in tumors, resulting in double-strand breaks in tumor DNA. Damage to the tumor DNA induces apoptosis (programmed cell death).

Results of a randomized Phase 2 trial of 23 patients with refractory, metastatic, unresectable biliary tract cancer who had relapsed following treatment with gemcitabine/cisplatin showed a one-year overall survival of 44.4 percent with etoposide toniribate versus 11.3 percent with best supportive care (BSC). Overall, 55.6 percent of patients met the primary endpoint of disease control compared with 20.0 percent who received BSC. The most common drug-related adverse events were leukopenia, neutropenia, thrombocytopenia, anemia, alopecia, fatigue and abdominal pain.

About Imbrium Therapeutics L.P.

Imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new pharmacologic and biologic therapeutics. We are pursuing oncology chemotherapeutics, treatments for disorders of the central nervous system, and non-opioid approaches to the management of pain. As an operating subsidiary of Purdue Pharma L.P., Imbrium strives to develop and bring to market new medicines that serve the unmet needs of patients, physicians and health systems worldwide. We have built a robust and diversified pipeline of investigational drug candidates, and we actively collaborate with industry and academic partners to identify and advance future impactful medicines. For more information, please visit

About Mundipharma EDO

Mundipharma EDO is part of the Mundipharma global network of privately-owned independent associated companies, which operate in over 120 countries worldwide. We develop treatments for patients around the world with rare or R/R cancer, investigating smart approaches to new cancer treatments from concept through to clinical development and regulatory approval.

We operate a lean, agile research and development model, empowering the team to form conclusions and make quick decisions with the aim of getting new therapies to patients as rapidly as possible. For more information please visit:

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Media Contacts:


Europe and RoW

Tiffany Fretwell

Communications Lead, Mundipharma

+44 (0) 1223 393 361

Helen Rae

Makara Health

Tel: +44 (0) 23 81 247 327

1 American Cancer Society. Key Statistics for Bile Duct Cancer. Retrieved from Accessed February 12, 2019.

2 U.S. Food & Drug Administration. Designating an Orphan Product: Drugs and Biological Products. Retrieved from Accessed February 12, 2019.

3 Electronic Code of Federal Regulations. 316.21: Verification of orphan-drug status. Retrieved from Accessed February 16, 2019.

4 Pape UF, et al. Journal of Clinical Oncology. 2019; 3(Supplement 4):264.

5 European Medicines Agency. Retrieved from Accessed February 15, 2019.  

6 Cholangiocarcinoma Foundation. Cholangiocarcinoma. Retrieved from Accessed February 12, 2019.