San Diego, Calif., March 01, 2003 - Chronic pain patients who took Ligand's (Nasdaq: LGND) once-daily pain product, AVINZA(R), needed less rescue medicine during active, waking hours than patients who took twice-daily MS Contin(R), according to a retrospective analysis presented in poster form yesterday at the annual meeting of the American Pain Society (APS) in Chicago.
Rescue medicines are routinely used to treat breakthrough pain that occurs while chronic pain patients are taking sustained-release opioid products such as AVINZA (morphine sulfate extended-release capsules), and MS Contin (morphine sulfate controlled-release, Purdue Frederick).
"Once-daily AVINZA has previously been shown to provide more stable plasma morphine concentrations than twice-daily MS Contin," said lead author Jacques Caldwell, M.D., of Radiant Research in Daytona Beach, Florida. "This retrospective analysis showed that more stable plasma concentrations may translate into better pain control and a reduced need for rescue medicines, especially during the waking period when patients are more susceptible to breakthrough pain of incident origin. Additional prospective studies are warranted."
Data were analyzed from two previously conducted clinical trials of patients with moderate to severe pain of nonmalignant origin. Results from the first study, a pharmacokinetic trial, were published in the Journal of Pain and Symptom Management (Vol. 23, pages 292-300, 2002). Rescue medicine use was assessed in a second previous trial, a randomized, double-blind cross-over study of 16 patients. Patients were treated for seven days with both AVINZA and MS Contin, and rescue medicines at a dose equal to 10% of the total daily morphine dose were allowed every two hours as needed. Rescue medicine doses were tracked on the last three days of therapy with each drug.
In the new analysis presented at APS, the researchers compared pharmacokinetic parameters and rescue medicine use over three time periods:
As expected, more rescue medicine was needed during daytime hours than nighttime hours. For both AVINZA and MS Contin, nighttime use of rescue medicines was about 30% of daytime use.
During the active, waking period between four and 14 hours after the morning dose, plasma morphine concentrations averaged approximately 18% higher for once-daily AVINZA than twice-daily MS Contin, and minimum concentrations were xx% higher for AVINZA than MS Contin. Consistent with this pharmacokinetic profile, patients taking AVINZA required fewer rescue medicines during this time period. Specifically, AVINZA patients required 51 doses of rescue medicines during active hours, while MS Contin patients needed 64 doses (p=0.14).
"Reduced need for rescue medicine during active hours with once-daily AVINZA relative to twice-daily MS Contin may be related to higher overall morphine concentrations in plasma, statistically significant higher minimum concentrations and reduced fluctuations with AVINZA," Dr. Caldwell said. "Given twice-daily, MS Contin appears to be susceptible to end-of-dose failure and lower overall morphine concentrations during the critical daytime period of highest rescue medicine use."
Use of rescue medicines was similar among patients taking AVINZA and MS Contin in the first four hours after the morning dose (21 rescue medicine doses for AVINZA patients and 19 for MS Contin patients), and in the inactive, nighttime period (32 rescue medicine doses for AVINZA patients and 31 for MS Contin patients). Overall, patients taking AVINZA averaged 2.2 doses of rescue medicines a day during the study, while patients taking MS Contin averaged 2.4 doses a day.
AVINZA and MS Contin produced comparable safety profiles. Adverse events were similar to those typically seen with opioid therapy.
AVINZA was approved in March 2002 by the U.S. Food and Drug Administration for the relief of moderate-to-severe pain in patients requiring continuous, around-the-clock opioid therapy for an extended period of time. AVINZA is co-marketed in the United States by Ligand and Organon, a business unit of Akzo Nobel.
About Ligand
Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, 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 (IRs) and Signal Transducers and Activators of Transcription (STATs).
Caution Regarding Forward-Looking Statements
This news release may contain certain forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Actual events or results may differ from Ligand's expectations. For example, there can be no assurance that results of subsequent studies of AVINZA will confirm results presented here, or that patient and physician acceptance of AVINZA will be achieved. Additional information concerning these and other risk factors affecting Ligand's business can be found in prior press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available via Ligand's internet site at 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.
Contact:
Michael Watts
Director, Investor Relations and
Corporate Communications
(858) 550-7850
mwatts@ligand.com
