Advancing another late-stage product deep into development, Inspire Pharmaceuticals Inc. began a Phase III trial of INS37217 Intranasal in patients with perennial allergic rhinitis (PAR).
The compound, which the company is testing in a number of delivery forms for several indications, in this case is being developed as a non-steroid, non-histamine approach to treating PAR - a $4.5 billion worldwide market opportunity.
"What distinguishes us is our product's very good safety profile," Inspire Vice President of Operations and Communications Mary Bennett told BioWorld Today. "At this point we have no known side effects, though there are potential side effects associated with most anything that's out there. I think it would be a very big plus if we can achieve a very clean side-effect profile."
Currently available treatments primarily include prescription and over-the-counter antihistamines, decongestants and nasal corticosteroids, many of which are associated with side effects such as sedation, rebound congestion, nervousness and insomnia. Because of the product's topical application through the spray, she said it degrades locally and therefore is not measured systemically in the blood.
The randomized, parallel-group, double-blind study is designed to evaluate the safety and efficacy of the P2Y2 agonist in a 10mg/ml nonpreserved nasal spray formulation, compared to placebo. Based on efficacy results from Phase I and II studies of INS37217, the 10mg/ml dose consistently showed the most robust effect.
The Durham, N.C.-based firm said it expects results in the second quarter of next year following the 28-day study, which will be conducted in about 630 patients at 24 U.S. centers. Its primary endpoint measures the total nasal symptom score (a composite of four nasal symptoms) averaged over the treatment period.
In August, Inspire reported that a Phase II trial of INS37217 Intranasal in PAR patients showed statistically significant improvement (p<0.05) in treatment groups compared to placebo for multiple PAR symptoms, including nasal blockage and stuffiness, facial pain and pressure, post-nasal drip and rhinorrhea. Also, a statistically significant improvement compared to placebo (p=0.012) was demonstrated for the mean total nasal symptom score (a composite of five nasal PAR symptoms) in the mid-dose group, which showed the most robust effect in Phase I.
The compound's activity appears beneficial in other indications as well, and findings from prior trials support its development in a number of areas.
"The nice thing about this product is that it has a very large potential market," Bennett said. "[Its indication] could be much broader than just allergic rhinitis - it could be seasonal and perennial allergic rhinitis, cold or sinusitis. So there's a lot of potential for expanding a label."
But she said Inspire first plans to pursue allergic rhinitis, given specific written FDA guidance based on prior approvals for seasonal and perennial allergic rhinitis.
"We are following that guidance closely, so there's a straightforward regulatory pathway," Bennett said. "We will have to run another study or two. We do hope to pursue both seasonal and perennial allergic rhinitis, but we don't really have timelines laid out yet for the rest of the program, though we can say that we will be moving it very aggressively."
Inspire reported earlier this month Phase II data for INS37217 Intranasal in patients with upper respiratory infection - the common cold. Results demonstrated a statistically significant improvement (p<0.05) compared to placebo in post-nasal drip and malaise at multiple doses and on multiple days over the 14-day study period.
The compound is being studied outside of the upper respiratory disorder indications as well.
"In this technology, we stimulate receptors to hydrate and clear mucosal surfaces," Bennett said. "Unlike an antiviral that would target the virus, our product actually addresses the symptoms. So regardless of the cause, our drug could be beneficial in relieving symptoms.
"We're studying the product in many mucosal surfaces."
Its INS37217 Respiratory product, designed to treat cystic fibrosis, has completed Phase I and Phase I/II trials. Inspire said results have shown the candidate to be well tolerated in children and adults, and is scheduled to begin a definitive Phase II trial by the end of this year.
Last month, Inspire entered a collaboration with Bethesda, Md.-based Cystic Fibrosis Foundation Therapeutics Inc., which will provide the majority of funding for the 28-day, double-blind, placebo-controlled, parallel group study, in exchange for post-commercialization milestone payments to be made following FDA approval.
A recent Phase I/II trial showed INS37217 Ophthalmic, when delivered as a single-dose intravitreal injection in patients with rhegmatogenous retinal detachment, to be well tolerated at all doses tested. Patients treated with INS37217 Ophthalmic showed improvement in the extent of retinal reattachment as determined by both objective measures. Patients treated with placebo showed no improvement as determined by the same two measures.
But another Inspire compound is closest to FDA review.
At the end of last month, Inspire said it would file a new drug application next year for its INS365 Ophthalmic, a later-stage product that acts as an eye drop for patients who suffer from chronic dry eye. Phase III data released in the summer indicated that INS365 Ophthalmic 2 percent demonstrated a highly statistically significant improvement (p<0.001) over placebo for the study's primary endpoint - corneal staining. (See BioWorld Today, June 19, 2002.)
An earlier Phase III study of the product failed to meet its primary objective.
Earlier this week Inspire said it would discontinue development of INS365 Respiratory for chronic bronchitis, a program that has been on hold since January, and instead would focus on higher-priority programs including dry eye and allergic rhinitis. The company's partner, Tokyo-based Kissei Pharmaceutical Co. Ltd., said it would discontinue Japanese development and returned to Inspire all Japanese rights to INS365 Respiratory.
The company's INS316 diagnostic product continues its Phase III development, which it began in May 2001. Not expected to close until the end of next year, the trial is studying the short-acting molecule's ability as a lung cancer diagnostic.
"We love the momentum that we're seeing right now," Bennett said. "We think that people are starting to see that there's a lot of value in the rhinitis and the dry eye programs."
Inspire's stock (NASDAQ:ISPH) climbed 68 cents Thursday to close at $7.90.