Next » | All Messages |  ADH Message Board Home | recommend post |  Ignore Poster

Adherex to Present ADH-1 and Eniluracil Data at 2007 ASCO Meeting

"Elucidating the mechanisms responsible for the previous failure of phase III clinical trials with eniluracil (EU) and development of a novel scheduling approach to optimize the efficacy of EU/5-fluorouracil (5-FU) combination therapy." Poster Number B13, Abstract No. 2557 by V. Guarcello, J. Fourie, M.J. Lawton, W.P. Peters, M.J. Heslin and R.B. Diasio to be presented today from 8:00 AM to 12:00 PM. As previously hypothesized by Adherex, this study demonstrates, that eniluracil produces profound inhibition of dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for the breakdown of 5-fluorouracil (5-FU), in both human tumor and normal tissues with no evident impact on the enzymes primarily responsible for the activation of 5-FU into an effective anti-cancer agent, uridine phosphorylase (UP) and thymidine phosphorylase (TP), at 12 to14 hours after eniluracil administration. These data support the importance of Adherex's proprietary dose and schedule approach for the optimization of combination therapy with these drugs.

"A phase I study evaluating a novel schedule of oral eniluracil (EU) combined with escalating doses of oral 5-fluorouracil (5- FU)." Poster Number C2, Abstract No. 2560 by J.R. Infante, S.F. Jones, M.J. Lawton, P. Wing, R.K. Malik, W.P. Peters and H.A. Burris III to be presented today from 8:00 AM to 12:00 PM. This interim analysis of the ongoing Phase I clinical study confirmed that a fixed 5 mg dose of orally administered eniluracil produces full functional inhibition of DPD in all studied patients. Further, 5-FU given orally 12 to 20 hours after the eniluracil administration produced predictable pharmacokinetics with a plasma half-life of approximately 3.5 hours, compared to a 5-FU plasma half-life of approximately 7-15 minutes when administered without pre-dosing with eniluracil. Twenty-eight patients have been enrolled to date for an aggregate of 62 cycles. No objective responses have been observed but six patients from the heavily pretreated patient population have experienced stable disease. The study is designed to assess the maximum tolerated dose (MTD) of oral 5-FU; an MTD has not yet been reached and the study continues.

"An open label safety and efficacy phase 2a study of the N-cadherin (N-cad) antagonist ADH-1 in subjects with N-cadherin expressing solid tumors." Poster Number H14, Abstract No. 3567 by Q. Chu, D.J. Jonker, J. Knox, G. Batist, P. Venner, K.N. Chi, L. Wood, J. Reeves, P. Kavan, E. Arrowsmith, H.A. Burris III, R.K. Malik and W.P. Peters to be presented today from 8:00 AM to 12:00 PM. The data from this North American Phase II clinical study included 40 patients with N-cadherin positive solid tumors who received an aggregate of 114 cycles of ADH-1 intravenously as a single agent at doses of 500 to 600 mg/m2 given weekly for cycles of three weeks. ADH-1 was well tolerated, displayed predictable pharmacokinetics and prolonged stable disease was seen in a number of patients with several tumor types, including hepatocellular cancer and renal cancer, with seven patients receiving seven or more cycles including one patient that continues on study.

"These three presentations highlight the progress we are making in our drug development efforts" said Dr. William P. Peters, Chairman and CEO of Adherex. "The two studies reported with eniluracil emphasize the importance of the dose and dosing schedule in optimizing the combination with 5-FU, as we predicted in our initial hypothesis. With ADH-1, having completed our single-agent programs where ADH-1 was well tolerated over a broad dosage range with hints of anti-tumor activity in a variety of tumor types, we are well underway with our clinical studies of ADH-1 in combination with a range of chemotherapeutic agents where our preclinical models have shown striking synergy. We are encouraged by the early clinical data, including a rapid complete remission in the very first melanoma patient treated with ADH-1 in combination with isolated limb infusion melphalan. This trial is, however, still very early in its accrual and more patients and further follow-up is essential for proper interpretation of any of the data."

Adherex is developing eniluracil to improve the therapeutic value and effectiveness of 5-FU, one of the most commonly used oncology drugs in the world. Adherex is currently evaluating the MTD of eniluracil in combination with 5-FU in a Phase I trial in solid tumors, with plans to initiate a Phase II trial of eniluracil + 5-FU in breast cancer immediately thereafter comparing the side effect profile and efficacy of eniluracil + 5-FU to capecitabine (Xeloda®). Adherex is also currently conducting a Phase I/II trial of eniluracil +5-FU in hepatocellular cancer in Asian patients.

Adherex is evaluating the synergy of ADH-1 in combination with chemotherapy in a Phase I trial of ADH-1 in three separate combinations: ADH-1 + docetaxel (Taxotere®), ADH-1 + carboplatin, and ADH-1 + capecitabine (Xeloda®). A Phase I study of ADH-1 in combination with regionally infused melphalan for the treatment of melanoma is also underway. Subsequent Phase II trial(s) of ADH-1 in combination with chemotherapy in one or more specific tumor types will follow and be based upon the results of the chemotherapy combination studies currently ongoing.

About ADH Adherex Technologies

Adherex Technologies Inc. is a biopharmaceutical company dedicated to the discovery and development of novel cancer therapeutics. We aim to be a leader in developing innovative treatments that address important unmet medical needs in cancer. We currently have multiple products in the clinical stage of development, including eniluracil, ADH-1 and sodium thiosulfate (STS). Eniluracil, an oral dihydropyrimidine dehydrogenase (DPD) inhibitor, was previously under development by GlaxoSmithKline for oncology indications. ADH-1, our lead biotechnology compound, selectively targets N-cadherin, a protein present on certain tumor cells and established blood vessels that feed solid tumors. STS, a drug from our specialty pharmaceuticals pipeline, protects against the disabling hearing loss that can often result from treatment with platinum-based chemotherapy drugs. With a diversified portfolio of unique preclinical and clinical-stage cancer compounds and a management team with expertise in identifying, developing and commercializing novel cancer therapeutics, Adherex is emerging as a pioneering oncology company. For more information, please visit our website at www.adherex.com.