Neurogen Corp. said top-line results from a Phase IIa trial of its oral C5a antagonist in asthma patients failed to demonstrate statistical significance.
Nevertheless, the company intends to further analyze data from the 142-patient trial to determine whether the candidate, NGD 2000-1, produced a therapeutic benefit in any subset of patients.
Despite the poor results, Neurogen's stock (NASDAQ:NRGN) held up fairly well, falling just 36 cents Tuesday to close at $8.72.
Of the Phase IIa, William Koster, company president and CEO, told BioWorld Today: "Clearly, this is not the most desirable news, but this is one of a number of [programs] we have going on within our organization. We are the first ones out there with the C5a antagonist. We feel this compound is a good regulator of the C5a receptor; it has all the appropriate pharmacokinetics and bioavailability - but again, we are the first ones out there and we are traveling in unchartered waters."
The Phase IIa was a randomized, double-blind, placebo-controlled study conducted in 16 clinical centers where patients were dosed for 28 days with either placebo or the drug at one of three dose levels twice a day. The primary endpoint measured forced expiratory volume in one second, the most frequently used lung function index for assessing bronchoconstriction or bronchodilatation in asthmatics. Secondary endpoints included an assessment of disease signs and symptoms and the use of albuterol, a common rescue medication used by asthma patients, the company said.
Jim Cassella, Neurogen's senior vice president of clinical research and development, told BioWorld Today the trial was a standard asthma study, "but at the end of the day, we did not see any statistically significant signals for treatment conditions in either the primary or secondary endpoints."
Meanwhile, Neurogen, of Branford, Conn., is conducting a Phase IIa for use of NGD 2000-1 in rheumatoid arthritis patients. Cassella expects to complete enrollment of the 48-patient trial during the first quarter.
As far as other indications go, Cassella said the company has a few possibilities in mind, but will make decisions later regarding which ones - if any - it will pursue.
"I think the beauty of the C5a mechanism is that it's involved with a lot of inflammatory processes," he said. "We picked RA and asthma because those are two very clear indications where we had the right alignment of the mechanism involved in the disease and the feasibility to do the studies. So we started both of these trials around the same time; we wanted to conduct them in parallel because we think there is a good probability that the mechanism is important for those indications."
The C5a program was discovered and is owned by Neurogen. It has not been partnered. Steve Davis, Neurogen's executive vice president and chief business officer, told BioWorld Today the company wanted to advance the program on its own.
However, Neurogen has a number of partnerships with other large firms. For example, Neurogen and New York-based Pfizer Inc. have enjoyed a decade-long relationship surrounding gamma-aminobutyric acid-based (GABA) drugs. Currently the partners are taking an insomnia drug through Phase I. (See BioWorld Today, Feb. 10, 1992; Dec. 11, 1997; and June 19, 1999.)
In other areas, Merck & Co. Inc., of Whitehouse Station, N.J., and Neurogen have a deal potentially worth $118 million to Neurogen to discover and develop pain medications that target the vanilloid receptor. (See BioWorld Today, Dec. 2, 2003.)
And Neurogen in the last month received a $1 million preclinical milestone payment from Aventis SA, of Strasbourg, France, in accordance with a deal to develop drugs that target corticotrophin-releasing factor (CRF-1) for depression, anxiety and other stress-related disorders.
Neurogen also has an unpartnered obesity program.