NPS Pharmaceuticals Inc. completed its new drug application (NDA) submission for Gattex (teduglutide) in short bowel syndrome (SBS), seeking a priority six-month review that could see the orphan drug on the market in the first half of next year.

But the Bedminster, N.J.-based biotech already has started planning for the drug's launch, said Francois Nader, president and CEO. 'We've had a plan set in motion' for the last 18 months or so, with top-line data reported from the Phase III Gattex trial in January 'triggering the initiation of commercial buildup.'

Not that NPS is jumping the gun. Nader described the firm's activities as a 'gated buildup' based on milestones such as the submission of the Chemistry, Manufacturing and Control portion of the NDA in August and the completion of the application this week. The next move will depend on whether the FDA grants priority review for Gattex in SBS, a decision expected around the end of February.

'That will determine our 2012 layout,' Nader told BioWorld Today.

So far, NPS has deployed medical science liaisons and has worked over the past two years to strengthen relationships with groups such as the Oley Foundation that can help the firm reach out to patients with SBS. And a few weeks ago, the firm brought on board a chief commercial officer, Eric Pauwels, whose resume includes a stint at Shire Human Genetics Therapies where he helped launch four orphan drugs.

SBS, which is estimated to affect about 10,000 to 15,000 people in the U.S., is a condition usually caused by extensive resection of the bowel that impairs the body's ability to absorb nutrients, forcing patients to undergo intravenous feeding – parenteral nutrition (PN) – to stabilize nutritional needs.

Gattex, a recombinant analogue of glucagon-like peptide 2, is aimed at reducing that need for PN by expanding the surface area of the intestine for the absorption of nutrients. In the confirmatory STEPS pivotal study reported in January, 63 percent of patients (27 of 43) receiving Gattex achieved a 20 percent or greater reduction in weekly PN vs. 30 percent (13 of 43) in the placebo arm (p = 0.002). Moreover, the drug's benefit appears to be cumulative: Data from the STEPS 2 extension trial showed that the response rate had jumped to 91 percent for patients completing 12 months of Gattex treatment. (See BioWorld Today, Feb. 1, 2011.)

The drug also has been well tolerated, though reports of three cancer cases during a presentation of an interim analysis from STEPS 2 sent NPS' stock tumbling in late October, a reaction Nader called 'somewhat paradoxical' to that of the study's investigators. 'They had known about the cases for some time, and there were no concerns.'

NPS pointed out that two involved cases of lung cancer in older patients with histories of smoking, while the third involved a case of metastatic adenocarcinoma of probable intestinal origin in patient with a history of Hodgkin disease who likely should have been declined from study participation. Moreover, no other cases of cancer have been observed, and a two-year rat carcinogenicity study came up clean. (See BioWorld Today, Nov. 1, 2011.)

Despite the market reaction, most analysts have since taken a more sanguine view. In a Nov. 9 research note, Leerink Swann's Joshua Schimmer called it a 'non-issue.'

A few, however, have raised questions. 'The absence of two completed carcinogenicity studies may be a risk to the Gattex filing,' noted analyst Jim Birchenough, of BMO Capital Markets, in a research report.

Either way, NPS is anticipating an FDA advisory meeting since Gattex is a new molecular entity and a first-in-class drug and is preparing to answer questions about the cancer findings since 'we don't know at this stage which way the panel will lean,' Nader said.

Gattex also is under review in Europe as Revestive. Partner Nycomed A/S, of Zurich, Switzerland, (now part of Takeda Pharmaceutical Co. Ltd.) filed a marketing authorization application in March and expects approval in mid-2012. Under the companies' 2007 licensing deal, NPS will be due a milestone payment on Revestive's first major European market launch. It also will earn double-digit royalties on all ex-U.S. sales. (See BioWorld Today, Nov. 1, 2007.)

Beyond Gattex, NPS also is looking to an NDA filing in late 2012 for a second orphan product. The firm reported strong top-line data from a Phase III study last month for Natpara (NPSP558), a bioengineered replica of human parathyroid hormone, in adults with hypoparathyroidism. (See BioWorld Today, Nov. 8, 2011.)

With two late-stage products, the company has been boosting its cash position over the past couple of years. It took advantage of the stock bump following the Gattex STEPS data to pull in $107 million in net proceeds from a public offering in April. And, in August, NPS took a $145 million advance on Sensipar (cinacalcet HCl) royalties from Amgen Inc., of Thousand Oaks, Calif. (See BioWorld Today, April 15, 2011, and Aug. 17, 2011.)

As of Sept. 30, NPS had about $190 million on its balance sheet.

'We've always been very opportunistic when it comes to financing,' Nader said. 'I believe we're in good shape.'

And come 2013, he added, hopefully the company will be receiving Gattex revenue and getting ready to launch Natpara. That same year should see a return of Sensipar royalties after NPS concludes its repayment to Amgen. 'So we should have a pretty significant royalty stream.'

Shares of NPS (NASDAQ:NPSP) closed Thursday at $5.63, down 5 cents.