FDA approves new treatment for advanced pancreatic cancer

October 22, 2015

The U.S. Food and Drug Administration approved Onivyde (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy.

CLINICAL PHARMACOLOGY

Mechanism of Action

Irinotecan liposome injection is a topoisomerase 1 inhibitor encapsulated in a lipid bilayer vesicle or liposome. Topoisomerase 1 relieves torsional strain in DNA by inducing single-strand breaks. Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase 1-DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death. In mice bearing human tumor xenografts, irinotecan liposome administered at irinotecan HCl-equivalent doses 5-fold lower than irinotecan HCl achieved similar intratumoral exposure of SN-38

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Safety & Efficacy

The effectiveness of Onivyde was demonstrated in a three-arm, randomized, open label study of 417 patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy. The study was designed to determine whether patients receiving Onivyde plus fluorouracil/leucovorin or Onivyde alone lived longer than those receiving fluorouracil/leucovorin. Patients treated with Onivyde plus fluorouracil/leucovorin lived an average of 6.1 months, compared to 4.2 months for those treated with only fluorouracil/leucovorin. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin.

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In addition, patients receiving Onivyde plus fluorouracil/leucovorin had a delay in the amount of time to tumor growth compared to those who received fluorouracil/leucovorin. The average time for those receiving Onivyde plus fluorouracil/leucovorin was 3.1 months compared to 1.5 months for those receiving fluorouracil/leucovorin.

The safety of Onivyde was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin.

ADVERSE REACTIONS

The most common side effects of treatment with Onivyde included diarrhea, fatigue, vomiting, nausea, decreased appetite, inflammation in the mouth (stomatitis) and fever (pyrexia).

Severe diarrhea occurred in 13% of patients receiving ONIVYDE in combination with fluorouracil and leucovorin.

Onivyde was also found to result in low counts of infection-fighting cells (lymphopenia and neutropenia). Death due to sepsis following neutropenia has been reported in patients treated with Onivyde.

Fatal neutropenic sepsis occurred in 0.8% of patients receiving ONIVYDE. Severe or lifethreatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE in combination with fluorouracil and leucovorin.

 WARNINGS AND PRECAUTIONS

Interstitial lung disease (ILD): Fatal ILD has occurred in patients receiving irinotecan HCl. Discontinue ONIVYDE if ILD is diagnosed.

Severe hypersensitivity reaction: Permanently discontinue drug for severe hypersensitivity reactions.

Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

The labeling for Onivyde includes a boxed warning to alert health care professionals about the risks of severe neutropenia and diarrhea.

Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer.

The FDA granted Priority Review and orphan drug designations for Onivyde.

Onivyde is marketed by Merrimack Pharmaceuticals Inc. of Cambridge, Massachusetts.

Reference:

  1. FDA News
  2. Prescribing information