With the initiation of a pair of pivotal efficacy and safety trials for ALTU-135, Altus Pharmaceuticals Inc. is gearing up to enter the $750 million worldwide pancreatic enzyme replacement market.

ALTU-135 still has a way to go before it enters the fray. Top-line data from its Phase III efficacy trial are expected in the second quarter of 2008, followed by data from its Phase III safety trial and a U.S. regulatory filing in the first half of 2009. But when ALTU-135's time does come, the drug could capture up to 50 percent of the market, according to a report from analyst Joseph Schwartz at Leerink Swann and Co.

That's because ALTU-135 would be the first microbially derived, recombinant option in a world of porcine-derived products. "If you look at the history in other markets, recombinant products almost always take the lion's share of the market over animal products," said Jonathan Lieber, vice president, CFO and treasurer at Altus.

ALTU-135, a blend of lipase, protease and amylase created with Altus' protein crystallization technology, could offer less variability than its porcine-derived competitors. Additionally, it is dosed in a single pill at every meal or snack while competitive products require four to five pills at a time.

The Phase III efficacy trial, in which the first patient has been treated, is a multicenter, randomized, double-blind, placebo-controlled study in about 150 cystic fibrosis patients with pancreatic insufficiency. Patients will receive one capsule of ALTU-135 at each meal. The primary endpoint is the treatment of fat malabsorption as measured by coefficient of fat absorption. Secondary endpoints include the treatment of protein and carbohydrate malabsorption as well as a decrease in the weight and frequency of patient stools.

The Phase III safety trial, which Lieber said will begin enrolling this quarter, is a year-long, open-label study in 240 patients, many of whom will roll over from the efficacy trial. The safety of ALTU-135 will be evaluated based on adverse events, physical examinations, vital signs and standard clinical laboratory testing.

The pivotal trials are expected to enroll within nine months at 50 trial sites. The trials follow a Phase II study in 129 patients in which ALTU-135 was well tolerated and improved fat (p <0.001) and protein (p <0.001) absorption as well as carbohydrate absorption.

Altus originally had hoped to start its ALTU-135 pivotal program in the second half of last year, but a manufacturing complication in July caused the company to delay the trials and knocked a quarter of the value off the shares. On Thursday, the Cambridge, Mass.-based company's stock (NASDAQ:ALTU) dipped 22 cents to close at $13.66. (See BioWorld Today, July 26, 2006.)

As of March 31, Altus reported $101 million in cash, cash equivalents and marketable securities. That figure does not include a public offering completed in April that netted the company $90 million. Lieber said Altus will use between $55 million and $65 million to fund operating activities in 2007, including the Phase III trials. (See BioWorld Today, April 20, 2007.)

If ALTU-135 proves successful, Altus plans to commercialize the drug in North America through an internal sales force of 70 to 80 representatives and managers. Most patients with pancreatic insufficiency also have cystic fibrosis, and Lieber estimated the company could cover the 115 cystic fibrosis treatment centers in the U.S. with about 35 reps. The remaining reps could be used to target chronic pancreatitis, an area in which Lieber said he sees "significant expansion potential."

In Europe, the countries of the former Soviet Union, Israel and Egypt, rights to ALTU-135 are held by Dr. Falk Pharma GmbH, of Freiburg, Germany. Lieber said the companies are "in discussions as far as a development plan for how to best move the product forward in Europe."

The market currently is dominated by Creon (Solvay Pharmaceuticals Inc.), Ultrase (Axcan Pharma Inc.) and Pancrease MT (McNeil Consumer & Specialty Pharmaceuticals), but changes are afoot. In 2008, IPO hopeful Eurand International SpA expects to launch a competitive product.

ALTU-135 may not be the only commercialization opportunity for Altus. Late last year, the company opted for a co-promotion clause when it licensed North American rights to its crystallized human growth hormone drug ALTU-238 to Genentech Inc., of South San Francisco, in exchange for $30 million up front (half cash, half equity) and up to $140 million in milestones. The joint development committee has not yet released a timeline for Phase III trials. (See BioWorld Today, Dec. 21, 2006.)

In preclinical development, Altus' most advanced candidate is ALTU-237, a crystalline formulation of an oxalate-degrading enzyme to address a disease in which patients have too much oxalate.

Altus plans to file an investigational new drug application this quarter, begin a Phase I trial in the third quarter and complete the trial by the end of the year.

If the ALTU-237 trial goes well, Lieber said it should create a "good comfort level" regarding ALTU-236 for phenylketonuria and ALTU-242 for gout, two preclinical drugs that use a similar approach to ALTU-237. Altus expects preclinical proof-of-concept data with both of those drugs this year and will move one into the clinic in 2008.