Adherex receives orphan drug designation for eniluracil to treat liver cancer

By E. Janene Geiss

Philadelphia, Dec. 21 - Adherex Technologies Inc. announced Wednesday that it has received orphan drug designation for eniluracil from the Food and Drug Administration.

The designation was granted for the use of eniluracil in combination with fluoropyrimidines for the treatment of hepatocellular cancer, according to a company news release.

The fluoropyrimidines include 5-fluorouracil (5-FU) and other 5-FU prodrugs. Adherex's global development plans for eniluracil, announced Nov. 16, include clinical trials in hepatocellular cancer, officials said.

In the United States, about 17,500 new cases of hepatocellular (liver) cancer are diagnosed each year, although the incidence is increasing.

Hepatocellular cancer is one of the world's most common tumors with more than 1 million new cases diagnosed annually. Currently, the therapies available to treat liver cancer are of limited effectiveness and the disease has a high mortality rate, officials said.

"Hepatocellular cancers have been shown to have very high levels of the enzyme dihydropyrimidine dehydrogenase (DPD), which may underlie the resistance of this cancer to 5-FU treatment. Since eniluracil irreversibly blocks DPD activity, the combination of eniluracil and 5-FU becomes an attractive approach to treating liver cancer," William P. Peters, chairman and chief executive officer, said in the release.

Peters said GlaxoSmithKline studied eniluracil and 5-FU in liver cancer in two phase 2 studies, using what is now known to be a sub-optimal dose and schedule. Even so, the results showed a high frequency and duration of stable disease, he said.

Using a more proper dose and schedule of eniluracil in combination with 5-FU, hepatocellular cancer may respond to treatment with 5-FU and this could provide an expedited route to approval for eniluracil in the United States, Peters said.

The FDA orphan-drug designation encourages companies to develop treatments for diseases that affect fewer than 200,000 patients in the United States per year.

The designation provides potential incentives such as funding for clinical studies, study design assistance, waiver of FDA user fees, substantial tax credits and, most importantly, up to seven years of market exclusivity upon regulatory approval.

Eniluracil was in-licensed from GlaxoSmithKline in July and is being developed to improve the therapeutic value and effectiveness of 5-FU, one of the world's most commonly used chemotherapies, by inhibiting its breakdown, officials said.

Although 5-FU is a mainstay of contemporary cancer therapy, it has some therapeutic drawbacks. These include that it must be given intravenously, it can cause severe and often dose-limiting side effects and it has variable blood and tissue levels that can impact its anti-tumor activity and safety profile, officials said.

In combination with eniluracil, 5-FU is orally active and has more uniform and prolonged blood and tissue levels, thereby potentially improving its side effect profile and anti-tumor effects, officials said.

The company expects to have eniluracil back in phase 3 trials by mid-2007.

Adherex is a Research Triangle Park, N.C., biopharmaceutical company dedicated to the discovery and development of novel cancer therapeutics.

© 2015 Prospect News.
All content on this website is protected by copyright law in the U.S. and elsewhere. For the use of the person downloading only.
Redistribution and copying are prohibited by law without written permission in advance from Prospect News.
Redistribution or copying includes e-mailing, printing multiple copies or any other form of reproduction.