New AMG 386 Data Demonstrate Promising Antitumor Activity in Patients With Recurrent Ovarian Cancer

AMG 386 Treatment Response Increased With Dose And Exposure

AMG 386 Moving Into Phase 3 For Recurrent Ovarian Cancer

Separately, Two Analyses Provide Evidence Of Biomarker As Predictor Of Tumor Response To Motesanib

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Jun 06, 2010, 09:00 ET

THOUSAND OAKS, Calif., June 6 /PRNewswire-FirstCall/ -- Amgen (Nasdaq: AMGN) today announced that AMG 386, combined with paclitaxel, demonstrated antitumor activity in a randomized Phase 2 trial involving 161 patients with recurrent ovarian cancer. The results are being presented for the first time in an oral presentation at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. (Abstract Number: 5000)

AMG 386 is a first-in-class investigational peptibody that is designed to block angiogenesis by inhibiting angiopoietin-1 and -2 (Ang1 and Ang2). Angiopoietins interact with the Tie2 receptor, which mediates vascular remodeling. Ang1 and Ang2 are thought to play opposing roles, and the maturation of blood vessels appears to be controlled by their precise balance.

"The reality of ovarian cancer is that 80 percent of women diagnosed in later stages will experience recurrence, often multiple times, and eventually die from the disease," said Beth Karlan, M.D., director of the Women's Cancer Research Institute at Cedars-Sinai's Samuel Oschin Comprehensive Cancer Institute and director of Cedars-Sinai Medical Center's Division of Gynecologic Oncology. "In this study, AMG 386 showed promising antitumor activity and extended progression-free survival."

Patients were randomized to receive paclitaxel via IV weekly, three weeks on and one week off, plus AMG 386 at 10 mg/kg (Arm A, n=53), AMG 386 at 3 mg/kg (Arm B, n=53), or placebo (Arm C, n=55).

Median progression-free survival (PFS), the study's primary endpoint, in the 10 mg/kg arm was 7.2 months versus 5.7 months in the 3 mg/kg arm and 4.6 months in the placebo group (80 percent CI, 0.59 - 0.98; p=0.17). The objective response rate, per RECIST, was 37 percent in the 10 mg/kg arm versus 19 percent in the 3 mg/kg arm and 27 percent in the placebo group. Response rate measured by serum CA-125 levels, per the guidance from the Gynecologic Cancer Intergroup (GCIG), was 71 percent in the 10 mg/kg arm versus 58 percent in the 3 mg/kg arm and 28 percent in the placebo group.

Grade 3 or higher adverse events (AEs), where the difference in incidence was more than five percent in the AMG 386 arm than the placebo arm, included: hypokalemia (Arm A/B/C percentages 12/11/4), peripheral neuropathy (10/2/4), anorexia (2/6/0), neutropenia (8/9/4), and dyspnea (2/9/4).

Other grade 3 or higher AEs of interest included thromboembolic events (arterial 2/2/0; venous 6/6/9). No grade 3 or higher hypertension was observed and there were no bowel perforations in patients treated with AMG 386. No treatment-related deaths occurred in the study.

The results of a population pharmacokinetic/pharmacodynamic analysis were presented separately in a poster at the Annual Meeting. This analysis suggests that investigation using higher doses of AMG 386 for patients with ovarian cancer is warranted. (Abstract Number: 5042)

Two Analyses Suggest Placental Growth Factor May be a Biomarker of Therapeutic Response to Motesanib

Results of two analyses evaluating biomarkers as predictors of response to treatment with motesanib were also presented at the meeting. Motesanib is an investigational, orally-administered, small molecule antagonist of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, platelet-derived growth factor receptor, and stem cell factor receptor. It is being investigated for its potential to inhibit the activity of all three VEGF receptors, which are key drivers of angiogenesis and lymphangiogenesis.

In the first study, a panel of five biomarkers was evaluated in patients with locally recurrent or advanced HER2-negative metastatic breast cancer who were treated with motesanib, bevacizumab, or placebo in combination with paclitaxel. Results showed that increases in circulating placental growth factor (PlGF) were associated with subsequent tumor response to treatment with motesanib plus paclitaxel. (Abstract Number: 1048)

In a separate study, a variety of biomarkers were evaluated in patients with progressive, advanced thyroid cancer, advanced non-squamous, non-small cell lung cancer, and locally recurrent or advanced metastatic breast cancer. Data from this analysis also suggested that PlGF elevation predicts clinical outcome across tumor types in patients treated with motesanib. (Abstract Number: 3037)

Motesanib is being developed in collaboration with Takeda and Millenium, the Takeda Oncology Company.

Webcast Information

Amgen will hold an analyst/investor event at a local venue in Chicago on Monday, June 7 at 7:30 p.m. Central Time to discuss data presented at ASCO. A webcast of the event can be found on Amgen's website at www.amgen.com, under Investors. The audio webcast will be archived and available for replay for at least 72 hours.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit http://www.amgen.com.

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