To Fill Pipeline Gaps, Astellas Narrows Focus And Takeda Spreads A Wider Net: Japan Earnings Roundup

PharmAsia News takes a closer look at pipeline updates from Japan’s two largest pharma companies.

TOKYO – Astellas Pharma Inc. shuttered a number of programs in 2011. The company terminated sales and marketing of Amevive (alefacept) for psoriasis in the U.S., handed off two diabetes compounds from its U.K. subsidiary Prosidion Ltd., ended a co-promotion of Sumavel DosePro (sumatriptan) with Zogenix Inc. for acute migraine and transferred manufacturing and marketing rights for three drugs, including melanin inhibitor Talthion, to Choseido Pharmaceutical Co. Ltd.

Most recently, Astellas dropped its global license for Vibativ (telavancin), and stopped development of OSI-906 in a Phase II program for hepatocellular carcinoma due to a poor risk-benefit balance; OSI-906 will continue in a Phase III program for adrenocortical carcinoma (Also see "Astellas Balks On Vibativ License, But Focus Shifts To Tivozanib And MDV3100" - Scrip, 12 Jan, 2012.).

In particular, Astellas has indicated it is looking for strategic alternatives for the diabetes and obesity research conducted by Prosidion, which it acquired when it bought OSI Pharmaceuticals LLC in June 2010. By entering into an option agreement with AstraZeneca PLC for the two investigational diabetes compounds, Astellas says it can return its focus to products like Vesicare.

Astellas announced in February 2011 it would exercise an option to take marketing responsibilities for Vesicare (solifenacin) away from GlaxoSmithKline Inc., four years before the deal was supposed to conclude. Astellas did not suggest any displeasure with GSK's efforts, but said taking over Vesicare's marketing responsibilities would strengthen Astellas and its products in the U.S. Astellas said during a Feb. 1 earnings call that it began marketing activities for Vesicare in January.

The transaction also should help Astellas build up strength in urology ahead of marketing approval for drugs like mirabegron, which Astellas highlights frequently as a product that can help it retain a strong market position in urology. Astellas will use 170 medical reps specifically for urology, nearly a third of the company's 530 sales reps.

However, Astellas' transition out of the diabetes sector hinges on the clinical trial success for a drug Astellas no longer wants. Astellas' Prosidion granted AstraZeneca an exclusive option to acquire PSN821 and PSN842, under development for type 2 diabetes. But the option depends on the outcome of tests for PSN821 and preclinical assessments. If the test outcomes are positive, AstraZeneca will acquire the assets from Prosidion in exchange for upfront payments and development milestones. Otherwise, AstraZeneca can walk away, minus an undisclosed, nonrefundable fee for the exclusive option (Also see "AstraZeneca Strengthens Diabetes R&D With Option On Astellas/Prosidion's Early-Stage Compounds" - Scrip, 22 Dec, 2011.).

Astellas decreased its Prosidion diabetes portfolio further by selling off a group of patents for early-stage DPP-4 inhibitors to Royalty Pharma for $609 million. With the sell-off, Astellas reduced Prosidion's staff in September from 120 employees to 50. The company is still trying to determine what to do with remaining preclinical compounds and the Prosidion diabetes facilities.

Shedding products and programs allows Astellas to focus on its key therapeutic areas, but also helps Astellas "enhance shareholder value," and propel itself from last year's financial low, in which the company "suffer[ed] the full impact from generics," Astellas CFO Yasumasu Masuda said during the earnings call.

The company is preparing filings for three products, MDV3100, tivozanib and a fixed-dose combination of slifenacin and tamsulosin in Europe. In addition, the company signed a deal last week with UCB Pharma SA for Cimzia (certolizumab) in Japan. Astellas will be the exclusive distributor for certolizumab in Japan, and the companies will co-develop and co-market the PEGylated TNF-alpha. UCB will receive an undisclosed upfront payment and clinical, regulatory and commercial milestone payments.

MDV3100 has already produced good interim results. The PREVAIL study is expected to last until at least September 2014, and Astellas currently plans to complete the study before filing. However the company also said it could consider filing based on interim results in the months ahead.

Questions arose during the earnings call on the sales strategy for MDV3100 in the U.S. The most recently released results put the drug in position for the post-chemo market, but the ongoing PREVAIL study has the potential to add pre-chemo patients as well. For now, Astellas said the target is post-chemo, but the PREVAIL study is "progressing steadily in Japan and Korea … and [Astellas] hopes to file for the approval as soon as possible to support the sales," Astellas said.

The company said MDV3100 exceeded expectations of the AFFIRM trial for prostate cancer in men previously treated with docetaxel chemotherapy, producing positive results on primary and secondary efficacy endpoints. Data presented at the Genitourinary Cancers Symposium in San Francisco Feb. 2 showed MDV3100 patients lived for a median of 18.4 months, compared to 13.6 months for men taking placebo, and MDV3100 showed radiographic progression-free survival of 8.3 months versus 2.9 months on placebo, according to Astellas.

Takeda's R&D Reshuffle

Japan’s largest pharma, Takeda Pharmaceutical Co. Ltd., has its own competitor to MDV3100, TAK-700, but Takeda's launch likely would come after Astellas’. Still, Takeda is optimistic about the drug's potential, including in combination with MDV3100.

Takeda Oncology advanced TAK-700 into two global Phase III trials for prostate cancer patients whose disease has metastasized.

"The results with [Astellas'] MDV3100 were very good and we anticipate that these two products, TAK-700 and MDV3100 could have similar outcomes, but could also potentially be used together in that the mechanisms of hormones suppression are different and therefore may be combinable for an even greater result," Millennium CEO Deborah Dunsire said during Takeda's Feb. 1 earnings call.

TAK-700 won't be first to market in the U.S. or EU, but Takeda believes it could still beat MDV3100 to market in Japan.

Takeda is in the process of restructuring its R&D organization, with eyes on filling a "substantial gap" in its mid-stage pipeline, according to Chief Scientific Officer Tadataka Yamada.

The idea is to integrate the Strategic Product Planning Department into the R&D arm, and in turn split up R&D into three groups: one that leads therapeutic targets; another called New Frontier Sciences that will "explore opportunities for bringing important early scientific platforms into the company"; and an office support arm.

Yamada says the reorganization will pull R&D out from being a "siloed, independent unit" to participate more in partnership conversations with biotechs and academia.

Yamada points to Takeda’s recent acquisition of Takeda Nycomed AS as a step to fill the mid-stage portfolio, but also indicated the company will continue with "aggressive in-licensing."

In December, Takeda purchased Intellikine Inc., which brought in two Phase I oncology compounds: INK1117, a selective inhibitor of the PI3K alpha isoform, and INK128, a dual inhibitor of mTOR complex 1 and mTOR complex 2 (Also see "Velcade’s New SubQ Formulation Means More To Takeda Than An Incremental Advance" - Scrip, 25 Jan, 2012.).

The reorganization also reflects integration of the Nycomed business. Takeda announced earlier in January that it would cut 2,100 jobs in Europe, in part to consolidate R&D sites (Also see "Takeda Shaves Off European Subsidiaries And U.S. Jobs On Japanese Approval Day" - Scrip, 18 Jan, 2012.).

While the Nycomed deal led to consolidation in R&D, it is also expanding other sectors of Takeda's business. Takeda announced in December it will build up a global vaccines business to take advantage of its widespread presence in new markets.

"We're actively engaged in discussions to cull market vaccines from established suppliers and to build a portfolio of novel vaccine candidates and vaccine development platforms through alliances," Yamada said.

Takeda is currently developing a Sabin-inactivated poliovirus vaccine and a human papillomavirus vaccine.

[Editor’s note: This story was contributed by PharmAsia News, which provides daily coverage of the Asia biopharmaceutical industry and regulatory policies. To learn more, sign up for a free trial.]