Avinza

SAN DIEGO -- Second Study in Patients with Moderate-to-Severe Osteoarthritis Demonstrates Improved Sleep for AVINZA Patients

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced the initial results from two studies to be presented in poster sessions at the American Pain Society annual meeting today in Boston. In the first study, its pain product AVINZA(R) showed better control of chronic pain and improved sleep in the initial results from this large comparator study comparing AVINZA given once daily to oxycodone CR(1) given twice daily. A second study demonstrated AVINZA's ability to provide better sleep as well as improved pain control for patients with chronic moderate-to-severe osteoarthritis.

The first study, referred to as ACTION (AVINZA Comparator Trials in Opioid Naive) is a randomized, multi-center, parallel-group study which enrolled 393 patients with moderate to severe chronic back pain and followed them for up to seven months. The study included a titration phase to allow all patients to have stable pain control at the initiation of the eight-week initial evaluation period. This was followed by a four-month extension phase to collect long-term pain control comparator information. It compared once-daily AVINZA (once-a-day morphine sulfate extended-release capsules) to twice-daily OxyContin(R) (oxycodone hydrochloride controlled-release). In initial results of the first phase of the study, with 212 evaluable patients (105 in the AVINZA arm and 107 in the oxycodone CR arm) followed through two months, the study showed that at lower, mean morphine-equivalent doses (72 mg AVINZA to 89 mg oxycodone CR), patients receiving AVINZA once daily demonstrated statistically significant better pain control (evaluated using the Brief Pain Inventory assessment instrument), statistically significant better quality of sleep (evaluated using the Pittsburgh Sleep Quality Index assessment instrument), and a statistically significant reduction in the frequency of required rescue medications. The final results from all patients in the study and the results from the extension phase to collect long-term comparator data are expected later this year.

Regarding around-the-clock pain control, the initial study results showed that in addition to maintaining a steady level of baseline pain control during the entire eight-week period, AVINZA showed additional pain control benefit throughout the day. The measurements at more frequent intervals (pre-dosing at zero hours and at six, nine and 12 hours post dosing) daily during weeks one, four and eight provided clear evidence of AVINZA's advantage as a once-a-day treatment showing statistically significant pain control benefit over oxycodone CR at nine hours (p<0.03) and 12 hours (p<0.01).

Overall use of rescue medication over the entire eight-week evaluation period was significantly lower for AVINZA than for oxycodone CR (p<0.01), again reinforcing the ability of AVINZA to maintain 24-hour pain control.

Patients treated with AVINZA enjoyed a statistically significant improvement in overall quality of sleep (assessed by the Global Quality of Sleep Index) over baseline and when compared with oxycodone CR (p = 0.05 at week one, p<0.01 at weeks four, eight and overall).

Side effects (incidence and severity) were recorded throughout the evaluation period. Compared both qualitatively and quantitatively, both AVINZA and oxycodone CR showed a very similar profile of side effects, indicating that the advantages of 24-hour pain control observed with AVINZA were not accompanied by an increase in the nature and number of patient-reported side effects.

"The initial study data confirms that AVINZA is truly a once-a-day sustained release opioid and as such allows patients to control their pain with relatively lower doses of opioid drugs and less need for overall rescue medications," said the study's lead investigator, Dr. Richard L. Rauck of Wake Forest University Baptist Medical Center. "This allows normal life activities while providing reliable, around-the-clock pain relief for patients."

A second poster will present data on a separate study that evaluated AVINZA's effects on various sleep measures for patients with chronic, moderate-to-severe osteoarthritis pain of the hip or knee who self-report trouble sleeping. This is a 30-patient, placebo/baseline-controlled, single blind study using both polysomnography (PSG) and subjective sleep measurements to assess and better quantify sleep parameters. Patients in the study had moderate-to-severe non-malignant osteoarthritis pain with sleep disturbances not due to another primary sleep disorder. All patients were on pain medications prior to the run-in placebo phase but had not previously had sustained-release opioids. This report covers the first 24 evaluable patients.

PSG studies were conducted in the sleep laboratory at California Clinical Trials in San Diego. The recordings included electroencephalograms and electro-oculograms to analyze multiple sleep parameters such as total sleep time, number of awakenings, latency to sleep, sleep stages and shifts, and REM sleep. Additional recordings were made to monitor EKG, blood pressure, air flow, and muscle and limb movement.

These PSG assessments validate and quantitate objectively the findings derived from subjective questionnaires provided by the patients in their self evaluation.

The initial study results show that subjects who have achieved stable pain control during 2 - 3 weeks of treatment after a placebo run-in period have an improved patient-reported pain control (P<0.001) and overall quality of sleep (p<0.001). The latter correlates with the quantitative PSG measurements which showed an increase in total sleep time, reduced latency to persistent sleep, decreased total wake time, decreased number of awakenings, an increase in sleep stage two duration, as well as no decrease in REM sleep duration from baseline.

"AVINZA not only provided excellent control of pain in each of our subjects, but they also self-reported the added benefit of improved quality and quantity of sleep," said clinical investigator Dr. Murray Rosenthal the PI and Medical Director of California Clinical Trials. "Several improved sleep parameters were documented by the PSG data that support the subjective improvement reported by patients being treated with AVINZA for chronic moderate-to-severe pain. These data suggest that AVINZA's effects upon sleep structure may distinguish this treatment for pain from others and warrants further exploration."

Andres Negro-Vilar, M.D. Ph.D., Ligand's executive vice president for research and development and chief scientific officer said, "The two studies being presented at the American Pain Society provide excellent, mutually-supportive information about the ability of AVINZA, as a once-a-day product, to provide good, around-the-clock pain control and improved sleep both subjectively and objectively through PSG analysis. The large comparator study of AVINZA once a day versus oxycodone CR twice a day clearly illustrates the advantages of a true once-a-day sustained-release opioid in different parameters of efficacy which, combined with a comparable safety profile, contribute to overall patient benefit."

About AVINZA

AVINZA (oral morphine sulfate extended-release capsules) is the first true once-a-day treatment for chronic moderate-to-severe pain in patients who require continuous, around-the-clock opioid therapy for an extended period of time. Approved by the FDA in March 2002, AVINZA consists of two components: an immediate-release component that rapidly achieves plateau morphine concentrations in plasma, and an extended-release component that maintains plasma concentrations throughout a 24-hour dosing interval. Ligand co-promotes AVINZA with Organon Pharmaceuticals USA Inc. in the United States. www.organonusa.com.

About Ligand

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to intracellular receptors. For more information, go to www.ligand.com.

Caution Regarding Forward-Looking Statements

This news release contains certain forward-looking statements that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These statements include those related to the initial results and conclusions of the studies, final study results, benefits and advantages of AVINZA, need for rescue medications, effects on sleep, relative doses and relative side effects. Actual events or results may differ from our expectations. For example, there can be no assurance that the final data, when analyzed, will confirm AVINZA's benefits, superiority, relative effective doses, side effects, need for rescue medications or effects on sleep compared to any competing product, that any subsequent studies will confirm results presented here, nor that AVINZA sales or acceptance will be affected by these results. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases as well as in public periodic filings with the Securities and Exchange Commission, available via www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

(1) Oxycodone CR evaluated in this trial was OxyContin(R) a registered trademark of Purdue Pharma L.P.

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