Speaking to the company’s first investor briefing focused on the gastrointestinal area, held recently in New York, Takeda Pharmaceutical Co. Ltd. president, COO and soon-to-be CEO Christophe Weber was clear: "GI is so important for us…and is seen as one of our key growth drivers along with oncology and the emerging markets."

The major Japanese firm expects GI drugs to contribute 28% of its prescription sales in fiscal 2017, up from 22% this fiscal year, largely on the back of expected blockbuster sales for its alpha-4-beta-7 integrin receptor inhibitor antibody Entyvio (vedolizumab) for inflammatory bowel disease (IBD).

The novel biologic is seen by Takeda as achieving peak global sales of at least $2 billion based on a 15-20% patient share, and is the first truly worldwide launch for the firm, marking a "new phase of globalization for Takeda," Weber told investors.

Partly on the back of prospects for the drug, Takeda’s share price has risen from around JPY5,000 at the start of the year to JPPY6,323 as of Mar.19, taking its market capitalization back towards the JPY5,000 billion ($41.5 billion) level, the highest in Japan’s pharma sector. Smaller Astellas, which has a higher proportion of foreign ownership, had overtaken Takeda’s market cap for a while late last year.

Takeda noted that the specialty GI market is expected to be worth around $28 billion in 2020, led by Crohn's disease, with the combined G7 country ulcerative colitis and Crohn's market worth around $10 billion by 2022. Biologics are seen accounting for 80% of this figure.

Not surprisingly, the firm sees the sector as attractive for further investment and one in which it told the meeting it is aiming to achieve global leadership.

The firm's major marketed GI products including Prevacid (lansoprazole) and pantoprazole (ex-Nycomed SPA) had combined sales of JPY299 billion ($2.46 billion) in fiscal 2013 (ended March 2014), Weber noted.

Meanwhile, Amitiza (lubiprostone) for constipation grew by 24% to JPY22.9 billion in the nine months, and the territorial expansion of Takeda's licensing deal with Sucampo Pharmaceuticals Inc. for the drug is expected to lead to launches in major emerging markets in 2017-18.

But while pantoprazole may be growing well (notably in IV form) in China, and the US and emerging markets are helping projected 33% growth for Dexilant (dexlansoprazole) over the fiscal 2011-14 period, Takeda's global sales of lansoprazole are declining following generic competition, with the proton pump inhibitor (PPI) slumping by 14% in the fiscal nine months ended Dec.31.

In general, Datamonitor sees Takeda's GI portfolio losing its current top sales value position to oncology over the period to 2023, given patent this and other patent expiries.

Blockbuster Status For Entyvio?

Much of the focus at the New York meeting was on Entyvio, which was approved in the US and EU last May for moderate to severe ulcerative colitis and Crohn's disease (including in TNF-alpha naïve patients). The drug generated global sales of JPY16.4 billion in the seven months after launch (it is now available in 14 countries), including $112 million in the June-December period in the US, where around 1.5 million suffer from IBD.

The number of IBD patients in this market is growing by around 8% annually (mainly in ulcerative colitis), while Takeda surveys have also shown interest among physicians in emerging markets in using the drug as a first-line biologic, investors heard.

In the US, around two-thirds of Entyvio's current use is in patients failing an anti-TNF-alpha therapy, and nearly two-thirds is in Crohn's, with physicians being encouraged by remission data, tolerability profile, broad indications and lack of boxed warnings, Takeda said. Entyvio's US volume share is currently around 6%.

Future development plans include the additional indication of mucosal healing in Crohn's, a subcutaneous formulation and a head-to-head trial versus adalimumab (AbbVie Inc.'s Humira). Entyvio is also moving into Phase III for primary sclerosing cholangitis, an inflammatory liver disease in which no therapy has shown prevention of progression.

In the meantime, Takeda expects limited impact from biosimilar anti-TNF-alpha products due to Entyvio's differentiated profile and mode of action.

But Datamonitor notes that biosimilar versions of Johnson & Johnson‘s Remicade (infliximab) could launch in GI indications this year, and that Entyvio's relative lack of efficacy in the Crohn's disease anti-TNF failure population in the GEMINI III trial could "dampen its commercial potential" and favor Humira in this setting. The planned comparative trial therefore appears aimed at this potential weakness.

Sales of Entyvio in the US, Japan and five major EU markets are seen by Datamonitor as reaching $439 million in 2021, dominated by the US, out of a total IBD patient-based market forecast of $8 billion.

Vonoprazan

Among the other new products highlighted at the New York meeting was the potassium-competitive acid blocker Takecab (vonoprazan), which was launched in Japan in February for a range of acid-related disorders.

The product is being co-promoted with Otsuka Pharmaceutical Co. Ltd. in seven indications and Takeda envisages peak annual sales of more than JPY60 billion. While the molecule is so far not being developed outside Japan, Takeda is "reviewing different options" and said the Japanese market remains large even after the entry of generic PPIs (which hold around a quarter of the PPI market).

In December 2014, the PPI sector in Japan was valued at around JPY290 billion, driven mainly by very strong growth for esomeprazole (AstraZeneca PLC/Daiichi Sankyo Co. Ltd.'s Nexium) ([A#28150310002]).

"We are still looking at the development plans" outside Japan, revealed Kirsten Detrick, vice-president for the GI therapeutic area within Takeda’s global commercial group, noting that many patients still have breakthrough symptoms and that partial PPI responders also provide an opportunity.

"The [Phase III] data [for vonoprazan] were really better than we expected…and we need to identify patient populations that can benefit," Weber added.

But while Takeda pointed to the convincing results and various other benefits including rapid action, potency, healing of erosive esophagitis, and less effect from drug metabolism polymorphisms (CYP2C19), others are not so sure.

P-CAB drugs in general do not have a particularly strong record, with various firms dropping development molecules (including AstraZeneca) due to what they concluded were limited benefits over existing therapies.

At the recent AstraZeneca Japan business briefing, country president Gabriel Baertschi was skeptical of Takecab's benefits over existing PPIs, and uncertain what niche the drug could find in the crowded market, given the endpoint of the Phase III program was non-inferiority to lansoprazole.

Datamonitor sees Takecab generating only modest revenues in Japan, peaking at $369 million in 2021.

Other Candidates

Beside the various lifecycle management programs, Takeda's GI pipeline also includes the oral STAT3 inhibitor TAK-114 (licensed from Natrogen Therapeutics International Inc.), which is currently in Phase II for moderate to severe ulcerative colitis patients failing 5-ASA drugs or conventional oral therapies.

Over the longer term, Takeda sees this as helping maintain GI as a core therapeutic area, in which it told the meeting that it is presently conducting more than 40 clinical trials.

Takeda Bigs Up Entyvio As Pillar Of GI Plans

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