Gleevec receives FDA priority review as first therapy to reduce recurrence of GI stromal tumors after surgery

East Hanover, August 27, 2008 — Novartis announced today that Gleevec® (imatinib mesylate) tablets has been granted priority review status by the US Food and Drug Administration (FDA) as the first therapy to be reviewed for use after surgery in kit-positive gastrointestinal stromal tumors (GIST). FDA priority review status is granted to therapies that could potentially fill a currently unmet medical need and accelerates the standard review timing from ten to six months1. Similar regulatory submissions have been filed in the European Union and Switzerland and will be filed in other countries shortly.

The Gleevec submissions are based on data from a Phase III, double-blind, randomized, multicenter, international study of more than 700 GIST patients who had surgery to remove their tumors. The results showed a dramatic 89 percent reduction in risk of kit-positive GIST returning after surgery (adjuvant setting) in patients treated with Gleevec versus placebo2.

In early 2007, the study met its primary efficacy endpoint, showing an advantage for Gleevec in recurrence-free survival. At that time, following the recommendation of the independent study data monitoring committee to stop the trial accrual early, the study investigators made public the interim results and offered Gleevec to patients receiving placebo3.

Approximately half of all patients with newly diagnosed GIST are considered candidates for surgical resection, or removal of their tumors. Of those who have the surgery, about half will suffer a recurrence4. If approved for this indication, Gleevec will be the first treatment option available to GIST patients after surgery to reduce the risk of disease recurrence or to possibly prevent the disease from returning.

“The dramatic clinical results from this study of Gleevec in the adjuvant GIST setting are especially encouraging when we consider the incremental benefit we typically see with other adjuvant therapies for solid tumors,” said Rainer Boehm, MD, Executive Vice President, North American Region Head, Novartis Oncology. “The adjuvant use of Gleevec, if approved, would represent an important advance in the ongoing post-surgery management of GIST.”

Gleevec is currently indicated in both the US and EU for the first-line treatment of metastatic or unresectable (inoperable) kit-positive GIST. If approved, the use of Gleevec for the treatment of GIST in the adjuvant setting would add to its eight current indications, which include Philadelphia chromosome- positive chronic myelogenous leukemia (Ph+ CML) and five other rare diseases. Novartis also has a therapy for the treatment of carcinoid tumors and acromegaly and multiple treatments in the pipeline targeting rare diseases.

Filing data

The study on which the regulatory filing is based compared the recurrencefree survival of GIST patients taking Gleevec 400 mg/day versus placebo for one year immediately following surgery. The results showed that 98 percent of patients receiving Gleevec remained recurrence free at one year following surgery compared to approximately 82 percent of those receiving placebo3. This shows that as a result of adjuvant therapy with Gleevec, there was an 89 percent reduction in risk of GIST returning2.
The study, known as ACOSOG Z90001, was conducted at multiple cancer centers throughout the US and Canada, under a Cooperative Research and Development Agreement between Novartis and the National Cancer Institute (NCI). The study was led by the American College of Surgeons Oncology Group (ACOSOG).
The investigators reported that Gleevec therapy was well tolerated by most patients, with side effects similar to those observed in previous clinical trials with Gleevec. These include nausea, diarrhea and swelling (edema)3. More information can be found at or

1. Fast Track, Priority Review and Accelerated Approval. US Food and Drug Administration • Center for Drug Evaluation and Research. cder/onctools/Accel.cfm. Accessed 31 July 2008.
2. Internal data (Novartis).
3. Z9001: A Phase III Randomized Doubleblind Study of Adjuvant STI571 (Gleevec®) Versus Placebo in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor (GIST). trials/ACOSOGZ9001. Accessed June 2008.
4. Van den Abbeele A., Benjamin R., Blanke C, et al. Clinical Management of GIST. Recurrence patterns and prognostic factors for survival. 2003;1-24.