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Javelin's Positive Intranasal Morphine Phase 2 Clinical Trial Data Presented at the American Pain Society Annual Meeting

New Secondary Analyses Show Rapid, Statistically Significant Analgesia Similar to IV Morphine in Postsurgical Pain

SAN ANTONIO, T.X. -- May 4, 2006 -- Javelin Pharmaceuticals, Inc. today presented new secondary analyses of a Phase 2b study of Rylomine(TM) (intranasal morphine) in 187 patients with moderate- to-severe post-surgical pain.

In addition to meeting the study's primary endpoint of a linear dose response for pain relief over 4 hours (TOTPAR4) as compared to placebo, new data presented today showed a rapid onset of analgesic action and duration of analgesic effect statistically superior (P <.05) to placebo and comparable to intravenous (IV) morphine.

"These data were recently presented to the FDA in an end of phase 2 meeting in support of Javelin's upcoming pivotal phase 3 program for Rylomine," said Dr. Daniel Carr, Javelin's Chief Executive Officer and Chief Medical Officer. "We are very excited at the results of these secondary analyses, which confirm that Rylomine's(TM) analgesic performance is similar to IV morphine. Unlike IV morphine, Rylomine offers patients the ability to self-administer effective pain medication using a simple, single-use device that avoids the need for painful injections, complicated technology, or the expense and discomfort associated with IV access."

In this study, 5 minutes after self administration of Rylomine 7.5 mg patients experienced statistically superior (P <.05) pain relief compared to IV morphine 7.5 mg and placebo as measured on the VAS and categorical scales. The duration of analgesic effect as measured by the median time to rescue medication for Rylomine 7.5 mg, Rylomine 15 mg and IV morphine 7.5 mg was 2 hours 4 minutes, 2 hours 19 minutes, and 2 hours 10 minutes, respectively. These median times to rescue medication for Rylomine treated patients were statistically significant compared to placebo (P <.05) and statistically similar to IV morphine.

The average redosing time was 4 hours 38 minutes for 1 nasal spray of Rylomine 7.5 mg and 5 hours and 59 minutes for 2 nasal sprays of Rylomine 15 mg. These data were presented today at the 25^th Annual Meeting of the American Pain Society (APS) in San Antonio, Texas. (Abstract #6237).

In this study, termed, MOR-002, 187 patients with moderate-to-severe post- surgical pain were randomized to receive a single dose of Rylomine 3.75 mg (n=24), Rylomine 7.5 mg (n=24), Rylomine 15 mg (n=24), Rylomine 30 mg (n=23), bolus IV morphine 7.5 mg (n=46) or placebo (n=46), and in the multiple dose phase received either 7.5 mg (n=90) or 15 mg (n=87) of Rylomine.

As previously described, single intranasal doses of Rylomine showed a progressive, statistically significant (P <.0001) analgesic dose response, as compared to patients given placebo, with analgesic effects similar to IV morphine for the higher intranasal doses.

Most adverse events were reported as mild-to-moderate in intensity. Local adverse events associated with nasal administration and reported by at least ten percent of patients, regardless of treatment group, included bad taste, nasal congestion, nasal discomfort, throat irritation, sneezing and rhinorrhoea.

General adverse events related to active drug (IV morphine or intranasal morphine), regardless of route of administration, were dose related and consistent with morphine's pharmacologic effects. General adverse events reported by at least 10% of patients in any treatment group included syncope, dizziness, nausea, sedation, oxygen desaturation, erythema, hypotension and vomiting. Oxygen desaturation was mostly mild-to-moderate and was resolved spontaneously or with nasal oxygen, but in no instance required intervention with naloxone.

Safety outcomes suggest Rylomine can cause morphine-like adverse events typically seen with other forms of parenteral morphine.

About the Study
A total of 187 post-bunionectomy patients from the United States were randomized in this multi-center, double-blind, placebo- and comparator- controlled study, to receive either a single bolus IV injection of morphine 7.5 mg, varying intranasal doses of Rylomine (3.75 to 30 mg), or placebo. After the single dose phase, patients received multiple doses of Rylomine (7.5 or 15 mg) over the course of the 24-hour treatment period.

In this blinded study, patients received treatments of which the identity was not known by either the investigator or the patient. Data from the primary endpoint and safety of this study were presented at the American Academy of Pain Medicine in San Diego, CA in February 2006.

Results of the step-down, multiple testing analysis indicate the minimally effective dose of Rylomine was 7.5 mg. Based on the ratios of pain relief (TOTPAR4) values, one spray of Rylomine 7.5 mg is approximately equivalent to a bolus IV injection of morphine sulfate 5 mg. Results from the multiple dose phase of the study indicated that both 7.5 and 15 mg Rylomine dose levels were effective at relieving pain over 24 hours with the higher dose showing superior efficacy and the lower dose showing better tolerability. To view a copy of the study posters, please visit http://www.javelinpharmaceuticals.com/press.html.

About Rylomine
Rylomine is a patient-controlled nasal spray that delivers a single, metered dose of morphine, an opioid analgesic used for the treatment of moderate-to-severe pain. After use, a negligible amount of morphine remains in the dispenser, avoiding the risk of scavenging and abuse of discarded devices.

Parenteral morphine is the standard-of-care in the management of acute pain, especially in the post-surgical setting, where analgesic requirements vary between individuals and may fluctuate even in the same patient. IV morphine analgesia has rapid onset, excellent efficacy, can accommodate variations in analgesic demand, and has risks that are well understood by medical personnel.

Morphine, like many drugs, is poorly absorbed across mucosal barriers and, in particular, the nasal membrane. Javelin's proprietary technology allows for nasal delivery of predictable therapeutic blood levels of morphine.

The key to this technology is ChiSys(TM), a carbohydrate polymer that, while pharmaceutically inert by itself, enhances the absorption of compounds across mucosal membranes, such as those found in the nasal cavity. The contribution of ChiSys(TM) to enhancing mucosal drug absorption reflects several factors including its potent mucoadhesive property, which prevents drug washout.

Rylomine is a novel formulation of morphine and ChiSys(TM) packaged in a single 7.5 mg unit nasal spray. Worldwide, no comparable formulation of morphine is available.


SOURCE: Javelin Pharmaceuticals, Inc.

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