Undeterred by a crammed proton pump inhibitor market already filled with established brand drugs, low-cost generics and over-the-counter alternatives, Takeda is moving ahead with the launch of a new PPI, Kapidex (dexlansoprazole).

Takeda is banking on the drug's novel dual delayed-release formulation to sufficiently differentiate the PPI in a crowded field that will soon include generic versions of its own Prevacid (lansoprazole).

To transform Kapidex into a blockbuster, however, Takeda will need to recreate a marketing coup similar to the one AztraZeneca maneuvered with the launch of its purple pill Nexium back when Prilosec went generic. Given today's price-centric market, yanking a rabbit out of a hat seems easier.

AstraZeneca backed the launch of Nexium with enormous marketing muscle, but a major difference between the switch strategies is that AstraZeneca also launched Nexium in 2001, nearly two years before generic versions of Prilosec became available, giving the company plenty of time to establish the drug in a market that did not include generics.

Kapidex To Shield Takeda From Prevacid Blow

The Japanese pharma announced FDA approval of Kapidex delayed release capsules Jan. 31 for the once-daily oral treatment of heartburn associated with symptomatic non-erosive Gastroesophageal Reflux Disease, the healing of erosive esophagitis and the maintenance of healed EE.

Kapidex, which Takeda expects to launch by March, is critical for the company. It is a follow-on to Prevacid, Takeda's second highest-selling drug, which is expected to face generic competition in the U.S. in November. In the first nine months of the year, Prevacid generated $2.5 billion (¥1=$0.01) for Takeda, $1.65 billion of which came from the Americas region. The drug accounted for about 19 percent of Takeda's total sales.

A series of upcoming challenges has Takeda scrambling for cover ahead of the upcoming revenue declines: loss of the Prevacid patent, lower sales of its top-seller, the diabetes drug Actos (pioglitazone), due to safety issues, anticipated patent expiration of Actos in 2011 and several development setbacks.

Takeda used to split Prevacid revenues and profits with Abbott under the TAP joint venture, but the companies dissolved the arrangement in April, with Takeda maintaining rights to Prevacid, Kapidex and an investigational gout drug filed with FDA, TMX-67, while Abbott maintained rights to Lupron Depot (¹ Also see "Takeda Buys Abbott’s Stake In TAP Joint Venture" - Pink Sheet, 19 March, 2008.).

All in all, given the number of low-cost alternatives, Takeda is likely to face challenges winning over physicians, patients and managed care providers when it comes to launching Kapidex.

PPIs Hit A Generic Iceberg; Prices Sink Fast

Thanks to plenty of marketing prowess, brand drug makers have been able to keep drugs afloat despite the availability of generic Prilosec (omeprazole) since 2003. But treading above water is getting harder to do as more drugs in the category go generic.

Generic versions of Wyeth's Protonix (pantoprazole) began impacting the market last year. Teva and Sun Pharmaceuticals launched a generic version at-risk at the end of 2007, which Wyeth countered with an "authorized" generic (² [A#00700050013], p. 28). This year, generic Prevacid is expected to join the fray. Nexium appears protected through 2014 through a patent settlement with Ranbaxy, although AstraZeneca is facing suits with other generic firms.

On top of the generic competition, the OTC market is also getting more crowded. Procter & Gamble's Prilosec OTC has been available since Prilosec went generic, but last year, private label alternatives joined the market. P&G reported a double-digit decline in sales of Prilosec OTC for the fiscal second quarter Jan. 30, citing private label competition.

Novartis has said it remains "committed" to launching an OTC version of Prevacid after the patent expires under a deal inked with TAP in 2005. The firm, however, has not released any details on the timing of the launch.

$14 Billion Market Doesn't Lose Its Luster Easily

Despite the maturing of the PPI category, the market for the drugs remains large, worth $13.9 billion as of Dec. 31, down 2 percent year over year, according to IMS data. Pricing pressures weighed on U.S. sales of Rx branded PPIs, however, including Prevacid, Nexium (esomeprazole) and Eisai/Johnson & Johnson's Aciphex (rabeprezole).

Sales of Nexium, the branded market leader, were down 8 percent to $3.1 billion in the U.S. for the year, AstraZeneca reported during its year-end sales and earnings call. Takeda reported higher sales of Prevacid for the first nine months of the fiscal year in the Americas Feb. 3, but only because of recordkeeping involving the dissolution of TAP. Otherwise, sales were down 21.4 percent year over year.

Generic omeprazole is the market leader in the category in terms of dispensed scripts with a 30 percent share. Nexium and Prevacid follow, with 26.9 percent and 14.5 percent shares, respectively. Generic pantoprazole has captured a 13.8 percent share, while Aciphex has a 5.4 percent share of the market as of Dec. 31, according to IMS.

Nexium prices declined about 11 percent in 2008, CFO Simon Lowth said during AstraZeneca's fourth quarter and year-end conference call Jan. 29. Based on managed care contracts for 2009, Nexium prices are expected to decline even further, he added, though "probably not in the double-digits."

"The unknown factors in the second half are whether the market sees multi-source generic pantoprazole or the launch of generic lansoprazole, both of which could add to some downward pressure," he said.

Can Dual-Delayed Release Trigger A Jumpstart?

Takeda is relying on a marketing edge for Kapidex, however: the drug's dual delayed-release formulation is the first for a PPI. Dexlansoprazole is an enantiomer of lansoprazole formulated with two types of enteric-coated granules, resulting in a concentration-time profile with two distinct peaks: the first occurs one to two hours after administration, followed by a second peak within four to five hours.

"By having the dual delayed-release and the extended period of time in the circulation, there is an improvement in symptomatic relief in patients who have GERD ... without the presence of esophageal erosions," Takeda's Gastroenterology Medical Director Charles Baum said.

In those patients, Kapidex demonstrated a greater improvement in 24-hour heartburn-free days and a reduction in both daytime and nighttime heartburn severity versus placebo, Baum said.

Takeda also pointed to a recent survey by the American Gastroenterological Association showing that about 40 percent of patients taking a PPI continue to experience breakthrough symptoms.

"The problem is that a lot of those folks are taking the medication twice a day in an attempt to get that extended release occurring, the kind of coverage in terms of circulating blood levels of the drug that we achieve with a single daily dose through the dual delayed release," Baum said.

The FDA approval for healing of erosive espophagitis was based on two clinical trials comparing Kapidex 60 mg and 90 mg daily to Prevacid 30 mg daily. In both trials, Kapidex 60 mg demonstrated overall higher healing rates at week eight versus lansoprazole. Non-inferiority was demonstrated in both studies, but superiority was only demonstrated in one, according to labeling.

For the other indications in maintenance of healed erosive esophagitis and symptomatic non-erosive GERD, Takeda studied Kapidex versus placebo. Kapidex is approved in 30 mg and 60 mg capsules. Side effects observed in clinical trials were similar to those seen with Prevacid.

AstraZeneca Isn't Cowering To Kapidex

AstraZeneca said it sees little threat to Nexium from Kapidex. "We feel good about the position Nexium has with patients and prescribers at this point," said Exec Director-Primary Care John McCarthy, pointing to AstraZeneca's clinical trial database that includes 12 head-to-head trials comparing Nexium to Prevacid, Protonix and Prilosec.

"In the space of the PPI promotion we hold a very strong advantage with the clinical data that we've generated with Nexium," he said. "With the launch of Kapidex, the data that [Takeda will] have is just against lansoprazole."

The exec also pointed to Nexium's strong formulary positioning, where the drug enjoys significant Tier 2 (preferred) coverage. "It really gets us to the point where most patients are paying $30 or less per month for Nexium," McCarthy said. "We see that as an important offering in a class that does have price pressure."

Takeda, for its part, has been shy when it comes to talking about sales goals or launch plans for Kapidex. During the company's quarterly call, Corporate Officer General Manager Hiroshi Takahara declined to answer most questions related to Kapidex, but did admit that given the challenging market, the drug will be priced competitively.

In a Feb. 3 research note, Deutsche Bank analyst Kenji Masuzoe weighed in, stating, "We will be watching the marketing strategy for recently approved GERD treatment agent Kapidex." However, the analyst noted, "No solution is seen to the patent exposure of Prevacid (November 2009) and Actos (January 2011)."

- Jessica Merrill (j.merrill@elsevier.com)

PPI Market Snapshot: Kapidex Joins The Party Fashionably Late

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