Takeda Announces Topline Secondary Endpoint Results from the Phase 3 TRINOVA-1 Trial of Trebananib (AMG 386) for Recurrent Ovarian Cancer

Osaka, Japan., November 5, 2014 – Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that its development partner, Amgen (NASDAQ: AMGN), has reported top-line secondary endpoint results of overall survival (OS) from the Phase 3 TRINOVA-1 trial evaluating trebananib plus paclitaxel versus placebo plus paclitaxel in women with recurrent ovarian cancer. The results from this primary analysis were first shared on November 4, 2014 by Amgen, Takeda’s co-development partner for trebananib.

The study results did not demonstrate a statistically significant improvement in OS. The median OS in the trebananib arm was 19.3 months versus 18.3 months in the control arm.

In the previously reported primary endpoint analysis, the data demonstrated a statistically significant difference in progression-free survival (PFS) for trebananib. In that analysis, patients treated with trebananib showed a 34 percent reduction in the risk of disease progression or death (HR = 0.66, 95 percent CI, 0.57, 0.77, p < 0.001). The median PFS was 7.2 months in the trebananib arm versus 5.4 months in the placebo arm.

“While we are disappointed that the trial did not show a statistically significant trend in overall survival, the positive progression free-survival data supports further analysis to fully understand trebananib’s potential as a treatment option for women with recurrent ovarian cancer,” said Kunihiko Takeyama, M.D., PhD, Head of Oncology Therapeutic Area Unit for Japan & North Asia. “Takeda is committed to developing innovative cancer therapies, and we look forward to our continued partnership with Amgen to evaluate the safety and efficacy of trebananib in patients with ovarian cancer in Japan.”

In the trebananib arm, the most frequently reported adverse events were localized edema, nausea and alopecia. The rate of discontinuation of investigational product due to adverse events was 20 percent in the trebananib arm versus seven percent in the control arm. No new safety risks were detected.

Data from a trial evaluating trebananib in combination with first-line chemotherapy treatment for patients with ovarian cancer (TRINOVA-3) is expected in 2015.

Trebananib is being co-developed by Takeda and Amgen. Under the terms of the collaboration agreement, Takeda has commercialization rights in Japan and Amgen has commercialization rights in the rest of the world.

TRINOVA-1 Trial Design (NCT01204749)

TRINOVA-1 (A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer) is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study evaluating trebananib in over 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off).

Other ongoing Phase 3 studies of trebananib include TRINOVA-2 and TRINOVA-3. TRINOVA-2 is evaluating whether trebananib plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival in recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. TRINOVA-3 is evaluating trebananib or placebo in combination with paclitaxel and carboplatin in the first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer.

About Trebananib

Trebananib is an investigational peptibody designed to inhibit the angiopoietin axis. The angiopoietin axis is involved in angiogenesis, a process used by the body to grow new blood vessels, which is also involved in the pathogenesis of several diseases. Trebananib is designed to bind to both angiopoietin-1 and -2 (Ang1 and Ang2), and inhibit their interaction with the Tie2 receptor.1,2,3 Ang1 and Ang2 each mediate separate actions upon binding with Tie2.4,5 Ang1 impacts vessel quality while Ang2 influences vessel quantity. The angiopoietins are also involved in lymphangiogenesis, the formation of new lymphatic vessels, which plays a key role in tumor metastasis.6

About Takeda

Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com. 

This press release contains forward-looking statements. Forward-looking statements include statements regarding Takeda's plans, outlook, strategies, results for the future, and other statements that are not descriptions of historical facts. Forward-looking statements may be identified by the use of forward-looking words such as "may," "believe," "will," "expect," "project," "estimate," "should," "anticipate," "plan," "assume," "continue," "seek," "pro forma," "potential," "target," "forecast," "guidance," "outlook" or "intend" or other similar words or expressions of the negative thereof. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors are cautioned not to unduly rely on such forward-looking statements.
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References:

1 Herbst R.S., Expert Opin Emerg Drugs. 2006;11:635-650.
2 Carmeliet P., Jain R.K., Nature. 2000;407:249-257.
3 Folkman J., Nat Rev Drug Discov. 2007;6:273-286.
4 Falcon B.L., Hashizume H., Koumoutsakos P., et al., Am J Pathol. 2009;175:2159–2170.
5 Ahmad S.A., Liu W., Jung Y.D., et al., Cancer Res. 2001;61:1255-1259. 
6 Huang H., Bhat A., Woodnutt G., et al.,  Nat Rev Cancer. 2010;10:575-585.

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