Shionogi & Co. will partner with Sage Therapeutics to develop and commercialize Sage’s SAGE-217 to treat major depressive disorder (MDD) and other indications in Japan, Taiwan, and South Korea, through a collaboration that could generate up to $575 million-plus for Sage.

The companies said their collaboration is aimed at speeding up development in key Asian markets for SAGE-217.

Shionogi and Sage disclosed their Asian collaboration last night, a day after Sage announced plans to launch an additional Phase III placebo-controlled trial in the U.S. in MDD in the second half of this year, in addition to its ongoing trial of the drug in women with postpartum depression (PPD), now designated a pivotal trial.

The new trial will assess the efficacy of two weeks of 20 mg or 30 mg SAGE-217 treatment compared to placebo in 450 patients with MDD, with four weeks of additional follow-up, Sage and Shionogi said.

The ongoing PPD trial (NCT02978326) is a multicenter, double-blind, placebo-controlled, randomized clinical study designed to evaluate two weeks of 30 mg of SAGE-217 treatment compared to placebo in 140 patients with PPD.

SAGE-217 is a next-generation positive allosteric modulator under development for MDD and certain other mood and movement disorders. According to Sage, SAGE-217 has been optimized for selectivity to synaptic and extrasynaptic type A γ-aminobutyric acid (GABAA) receptors and a pharmacokinetic profile intended for daily oral dosing.

SAGE-217 won the FDA’s Breakthrough Therapy Designation in February, based primarily on positive results from a Phase II, placebo-controlled trial of SAGE-217 in 89 adults with moderate-to-severe MDD.

In that trial (NCT03000530), SAGE-217 met the primary endpoint with a statistically significant mean reduction in the Hamilton Rating Scale for Depression (HAM-D) 17-item total score from baseline at day 15 in the SAGE-217 group, compared to placebo. Statistically significant improvements were observed in the HAM-D score compared to placebo by the morning following the first dose through week 4 and the effects of SAGE-217 remained numerically greater than placebo through the end of follow-up at week 6, according to Sage and Shionogi.

Under its collaboration with Sage, Shionogi agreed to oversee all clinical development, regulatory filings and commercialization of SAGE-217 for MDD, and potentially other indications, in Japan, Taiwan and South Korea.

$90 Million Upfront

In return, Shionogi agreed to pay Sage $90 million upfront and up to $485 million in payments tied to achieving development and commercial milestones. Sage is also eligible for tiered royalties on sales of SAGE-217 in Japan, Taiwan, and South Korea, if development efforts are successful, with tiers averaging in the >20% range, subject to other terms of the agreement.

Shionogi has also granted Sage additional rights to co-promote SAGE-217 in Japan across all indications. Sage maintains exclusive rights to develop and commercialize SAGE-217 outside of Japan, Taiwan, and South Korea, the companies said.

“We are pleased to collaborate with Shionogi, a company that shares our excitement at the opportunity to work together to accelerate development and broaden geographic access to a potentially paradigm-shifting treatment for depression,” Sage CEO Jeff Jonas, M.D., said in a statement. “By working together, we believe we can expand the global footprint for SAGE-217 alongside our ongoing efforts in the U.S. and E.U.”

Shionogi president and CEO Isao Teshirogi, Ph.D., added that the partnership builds upon his company’s focus on treatments for psychiatric disorders.

The treatments include the antidepressant duloxetine, a selective serotonin and norepinephrine reuptake inhibitor that the company co-markets in Japan with Eli Lilly as Cymbalta®, and the ADHD treatment guanfacine, a selective alpha-2A adrenergic receptor agonist that Shionogi co-markets as Intuniv® in Japan with Shire, soon to be acquired by Takeda Pharmaceutical.

During the fiscal year that ended March 31, Shionogi generated ¥23.5 billion ($213 million) in sales from Cymbalta—16.9% of the company’s total ¥139.2 billion ($1.26 billion) in sales from prescription drugs—and ¥1.9 billion ($17.2 million) in sales from Intuniv.

“This collaboration, if successful, will enable us to move one step closer in realizing a more vigorous society in which patients in need are provided the potential for relief from the psychological uncertainty of depression allowing the possibility of fulfillment of one’s innate ability,” Dr. Teshirogi said.

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