The failure of a gastrointestinal compound to meet its primary endpoint in a Phase III study did not deter Nycomed from sticking with a $185 million deal with NPS Pharmaceuticals Inc., the firms said Wednesday.
Although the Phase III results of NPS's Gattex (teduglutide), an analogue of glucagon-like peptide-2, demonstrated efficacy in patients with short bowel syndrome (SBS) receiving a low dose of the compound, the drug failed to show statistical significance in a higher dosage. (See BioWorld Today, Oct. 12, 2007.)
The study's criteria for conducting the statistical analysis of the primary endpoint required that the results for the high-dose group show statistical significance before the results of the low-dose group could be considered.
Under an agreement formed in September, Zurich, Switzerland-based Nycomed had the option to split from the deal within two weeks of the announcement of the Phase III results and forgo paying $25 million of a $35 million up-front payment. (See BioWorld Today, Sept. 27, 2007.)
But after reviewing the Phase III data over the past few weeks, Nycomed is "quite confident in the future" development process for Gattex, and will proceed with the terms of the agreement to develop and market the compound outside North America, said spokesman Tobias Cottmann.
"With additional clinical data we can very well prove that it is effective," he told BioWorld Today. "We are confident, and that's why we want to continue" with the deal, Cottmann said by phone from Zurich.
Nycomed now will pay the $25 million balance for the up-front payment, both firms confirmed.
The deal calls for Parsippany, N.J.-based NPS to retain the rights to develop and market the compound in the U.S., Canada and Mexico.
If Gattex attains certain regulatory milestones for the SBS indication, and the compound is successfully developed for other indications and achieves certain sales-based milestones, NPS could bank an additional $150 million.
The New Jersey biotech also could earn double-digit royalties for sales of Gattex outside North America.
The firms are splitting equally the costs to develop Gattex for other gastrointestinal indications, the companies said.
NPS CEO Tony Coles said his firm is planning to discuss the results of the Gattex SBS Phase III study with the FDA so that the company can "proceed as rapidly as possible with the next steps required to obtain regulatory approval" in the U.S.
NPS spokeswoman Brandi Simpson declined to comment on when her firm planned to meet with U.S. regulators about Gattex.
The Phase III study examined Gattex in 83 patients with parenteral nutrition-dependent SBS, a condition resulting from the surgical removal of significant portions of the bowel following injury or illness.
Patients were randomized to receive daily subcutaneous injections of 0.05 mg or 0.1 mg of Gattex per kilogram of body weight or a placebo. The clinical efficacy endpoint of the study was a reduction of at least 20 percent in parenteral nutrition, or intravenous feeding.
In the low-dose group, 46 percent of patients showed a 20 percent or better reduction in parenteral nutrition after 24 weeks compared with 6 percent in the placebo group. However, only 25 percent of patients in the high-dose group responded and showed a trend in the difference between the treatment and placebo groups.
With NPS's "successful financing and asset monetization activities and Nycomed's commitment to Gattex," Coles said, his firm is in an "excellent position" to complete the U.S. registration of the compound in SBS and pursue its development in multiple indications.
NPS recently announced that it would receive $30 million from London-based AstraZeneca plc under an agreement to end a partnership on another investigational compound. The biotech said it would use those funds to augment its development program for Gattex and other late-stage products. (See BioWorld Today, Oct. 10, 2007.)
NPS said it also is pursuing development of Gattex as a potential therapy for chemotherapy-induced gastrointestinal mucositis in patients with cancer and necrotizing enterocolitis in preterm infants.
Gattex will be an "important addition to our product pipeline," Nycomed CEO Hakan Bjorklund said in a statement, adding that his firm expects the compound to "complement our development and marketing capabilities in the gastroenterology field."
The deal with NPS is part of Nycomed's new R&D strategy to partner with other firms at all stages of product development, which the Swiss firm introduced after it acquired Germany-based Altana Pharma AG in January, Cottmann said.
"We want to have the larger proportions of ideas and projects from the external world," he said, adding that Nycomed has established a "special pipeline sourcing unit to work on that and to insource products at the very early stages in the discovery up to the late phases."
Nycomed also has partnered with NPS on a deal to market the New Jersey biotech's recombinant human parathyroid hormone Preotact outside of the U.S., Japan and Israel. Preotact was granted marketing approval in Europe in May 2006.
NPS is seeking to market the compound in the U.S. under the brand name Preos.