Inspire Pharmaceuticals Inc. reported less-than-rousing results from a Phase III trial in allergic rhinitis.
The Durham, N.C.-based company reported that a 630-patient, multicenter study of INS37217 Intranasal in perennial allergic rhinitis patients failed to meet its primary endpoint as the product did not significantly reduce the total nasal symptom score over the 28-day treatment period against placebo. The news dropped Inspire's shares (NASDAQ:ISPH) down $1.37 Tuesday, or 8.5 percent, to close at $14.78.
"It's not that the product did not have activity, because it absolutely did," Inspire CEO Christy Shaffer said during a conference call. "It was not that it was worse than placebo - they both improved. We couldn't show the nice delineation and differentiation that we would have liked to have seen in the trial."
While the company did not release specific findings, Shaffer acknowledged during the call that the "p" values were "nowhere close to being significant." But she added that the subjective nature of the patient reporting system employed in the trial could have had a negative effect on the outcome.
"It is not uncommon to have a failed study in this type of indication," Shaffer said, noting that a Phase III trial of Nasonex (from Schering-Plough Corp.) showed no symptomatic benefits at any dose. The total nasal symptom score used in the INS37217 study was a composite of four symptoms: rhinorrhea (runny nose), nasal congestion, nasal itching and post-nasal drip. The reduction in symptoms for the P2Y2 receptor agonist was less than that seen in previously reported Phase I and II studies in perennial allergic rhinitis and common cold.
While the company continues to sift through the data in order to determine the roots of the different findings, some positive results from the latest study were of note. The randomized, parallel-group, double-blinded trial found the 10mg/mL nonpreserved nasal spray formulation to be safe and well tolerated. Including prior studies of the intranasal formulation, Shaffer said Inspire has collected a safety data package in more than 800 patients that could prove useful if the product continues to move forward.
But the company stressed that the program's outlook is unclear.
"At this point I think it's really too early to say what the future of that program would be," Mary Bennett, Inspire's vice president of operations and communications, told BioWorld Today. "We certainly aren't going to move forward a drug based only on safety, so we have a lot of work yet to do to evaluate the efficacy results."
Data also showed patients receiving INS37217 Intranasal had a lower incidence of respiratory-related infection as compared to patients on placebo. Inspire said it plans to further evaluate the anti-infective findings, which were seen in both viral and bacterial infections. The company has studied the product in patients with the common cold, with positive results uncovered in a Phase II trial.
"This could be a potentially meaningful finding with respect to other clinical indications that we have been considering for this product," Shaffer said. "While this is encouraging, we will carefully explore all of our options prior to proceeding with any additional studies."
Inspire plans to drop back and re-evaluate its program for the intranasal formulation of the compound in conjunction with a team of clinicians. But in spite of the setback, other formulations of INS37217 continue to be studied for cystic fibrosis and retinal detachment.
Both programs are in Phase II, with plans to begin a second Phase II study of INS37217 Ophthalmic in retinal disease later this year. Shaffer said about 10 patients have been enrolled in the cystic fibrosis program, and Inspire expects to complete enrollment in the 92-patient trial of INS37217 Respiratory by the end of the year.
"We have very nice underlying science in all these programs," Bennett said. "We're quite confident about the actual activity of the P2Y2 receptor agonists, with evidence in all of our studies that they stimulate the receptor and promote mucociliary clearance and mucosal hydration. The question then is not whether the drug in that sense works, but in fact whether that mechanism is useful in treating a clinical disease."
Shaffer added that the disappointing findings would not hinder the advancement of the company's other programs.
Inspire's near-term priorities include plans to submit a new drug application for diquafosol tetrasodium (INS365) by the middle of the year. Another P2Y2 receptor agonist, the dry-eye product is one subject of a co-promotion deal with Allergan Inc., as is Irvine, Calif.-based Allergan's Restasis. Worldwide sales of its dry-eye product, which received marketing clearance in December, eventually will generate royalties for Inspire, excluding larger Asian markets.
Restasis sales began in April, meaning Inspire will see its first royalty payments a year later. It will receive royalty payments from diquafosol sales upon its release. (See BioWorld Today, June 28, 2001, and Oct. 31, 2002.)
While Inspire has yet to opt into the co-promotion arrangement with Allergan for those products, Bennett said Inspire intends to enter the deal. Osaka, Japan-based Santen Pharmaceutical Co. Ltd. is developing diquafosol in that nation and nine other countries in Asia.
Using a portion of $63.1 million raised through a public offering two months ago, Inspire said it would build a 60-person sales force in the fourth quarter to market Restasis and eventually diquafosol as well. To that end, Bennett said Inspire already hired a vice president for sales and marketing. (See BioWorld Today, March 17, 2003.)
Inspire has one other ongoing clinical program, studying the compound INS316 in a Phase III trial as a lung cancer diagnostic product.