antiquity
05-01-2002, 11:45 PM
AVINZA Phase III Study Published in Leading Pain Journal Shows that New Drug Reduces Pain, Improves Sleep in Osteoarthritis Patients Compared to Placebo
Business Editors/Health & Medical Writers
BIOWIRE2K
SAN DIEGO--(BW HealthWire)--May 1, 2002--Ligand's new once-daily pain product, AVINZA(TM) (morphine sulfate extended-release capsules), reduced pain and improved overall quality of sleep in patients with chronic, moderate-to-severe osteoarthritis (OA) pain compared to placebo, according to a Phase III study published in The Journal of Pain and Symptom Management (Vol. 23, No. 4, 2002).
Once-daily AVINZA was approved in March 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. Ligand plans to launch AVINZA this quarter.
In the article, researchers describe a randomized, four-week study evaluating the safety and efficacy of AVINZA, MS Contin(R) (MSC, morphine sulfate controlled-release, Purdue Frederick), and placebo in 295 patients with chronic, moderate-to-severe OA pain. Patients had failed to achieve adequate response to NSAIDs and acetaminophen or had previously received opioid therapy. Patients were given AVINZA 30 mg. once daily in the morning (QAM) or evening (QPM), MSC 15 mg. twice daily, or placebo. No dosage adjustments were allowed.
According to the WOMAC OA Index Pain Visual Analogue Scale, AVINZA QAM (17% scale improvement), QPM (20%) and MSC twice-daily (18%) demonstrated a statistically significant reduction in pain from baseline over the four-week study compared to placebo (4%). Less pain was reported in all treatment groups by week one, and further reductions in pain were evident throughout the four-week period compared to baseline. Analgesic efficacy was comparable between once-daily AVINZA and twice-daily MSC. According to Overall Arthritis Pain Intensity Scores, AVINZA QAM (26% improvement), QPM (22%) and MSC twice-daily (22%) reduced pain compared to placebo (14%), although these differences were not statistically significant.
AVINZA and MSC also provided improvements in all sleep measures compared to placebo. In addition, AVINZA QAM demonstrated a statistically significant improvement in overall quality of sleep compared to twice-daily MSC at weeks one and four. Sleep disturbances occur in 50-70% of patients with chronic pain. The investigators evaluated overall quality of sleep, need for sleep medication, hours of sleep, difficulty falling asleep, and awakening in the morning and evening due to pain.
"Poor sleep may lead to increased pain, physical disability, and psychological disturbances that accompany chronic pain," said lead author Jacques Caldwell, M.D., of Radiant Research in Daytona Beach, Fla. "In this study, the greatest improvements in sleep measures were experienced by patients taking AVINZA QAM, and further studies are warranted."
Adverse events, most commonly nausea and constipation, were consistent with those commonly observed with opioid therapy and generally similar among the active treatments. A total of 58 patients (20%) withdrew from the study due to adverse events. Six patients experienced a serious adverse event but only one, who was hospitalized for constipation, experienced an adverse event possibly related to study drug (AVINZA QPM).
Open-Label, 26-Week Extension Study of AVINZA
Patients who completed the four-week trial were eligible to participate in an open-label, 26-week extension study of AVINZA QAM or QPM. Of 184 eligible patients, 181 chose to participate in the extension study, during which patients could increase their dose to optimize pain control. Eighty-six patients completed the extension study; of these, 42 (49%) remained on the initial 30 mg. dose of AVINZA. "Nearly half of patients who completed the extension trial remained on the initial once-daily dose, which suggests this modest amount of morphine was adequate for many patients for controlling OA pain over 30 weeks," Dr. Caldwell said.
Improvements in pain intensity, stiffness and physical functioning were observed in the first week of the extension trial and were sustained in all subsequent weeks. Mean clinical improvements through week 12 corresponded with increases in the mean daily dose of AVINZA. In weeks 12 through 30, pain intensity, physical function and stiffness remained stable, as did the average daily dose of AVINZA (approximately 50 mg). "Stable analgesia was observed in the open-label trial, which was consistent with the relatively stable AVINZA dose following dose titration to achieve optimal pain control," Dr. Caldwell said. "This suggests that tolerance was not experienced by the majority of patients in this study."
Adverse events were similar in the QAM and QPM groups, with constipation and nausea the most frequently reported. Of the 181 patients randomized, 56 (31%) withdrew from the study due to adverse events. Four patients experienced serious adverse events that were considered possibly related to AVINZA: enteritis and gastritis; dehydration, diarrhea, hyponatremia, nausea and vomiting; constipation; and vomiting, respectively. All four patients recovered.
Other Recent AVINZA Publications
Recently published articles on AVINZA (formerly Morphelan(TM)) include:
Russell K. Portenoy, M.D., et al, "Steady-State Pharmacokinetic Comparison of a New Extended-Release, Once-Daily Morphine Formulation, AVINZA(TM), and a Twice-Daily Controlled-Release Morphine Formulation in Patients with Chronic Moderate-to-Severe Pain," Journal of Pain and Symptom Management, Vol. 23, No. 4, 2002.
Lise Eliot, Ph.D., et al, "Pharmacokinetic Evaluation of a Sprinkle-Dose Regimen of a Once-Daily, Extended-Release Morphine Formulation," Clinical Therapeutics, Vol. 24, No. 2, February 2002.
Lise Eliot, Ph.D., et al, "Steady-state pharmacokinetic comparison of a new once-daily, extended-release morphine formulation (Morphelan(TM)) and OxyContin(R) twice daily," Journal of Oncology Pharmacy Practice, Vol. 7, 2001.
Lise Eliot, Ph.D., et al, "Evaluation of Two Loading-Dose Regimens of Morphelan(TM) in Healthy Volunteers," The Journal Of Applied Research, Vol. 2, No. 1, Winter 2002.
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).
Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm (http://www.businesswire.com/cnn/lgnd.htm).
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 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 (http://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.
--30--jf/sd* dw/sd
CONTACT: Ligand Pharmaceuticals Incorporated, San Diego
Michael Watts, Director, Investor Relations and
Corporate Communications
858/550-7850
mwatts@ligand.com
KEYWORD: CALIFORNIA
INDUSTRY KEYWORD: BIOTECHNOLOGY MEDICAL PHARMACEUTICAL PRODUCT
SOURCE: Ligand Pharmaceuticals Incorporated
Today's News On The Net - Business Wire's full file on the Internet
with Hyperlinks to your home page.
URL: http://www.businesswire.com
05/01/2002 19:19 EASTERN
Business Editors/Health & Medical Writers
BIOWIRE2K
SAN DIEGO--(BW HealthWire)--May 1, 2002--Ligand's new once-daily pain product, AVINZA(TM) (morphine sulfate extended-release capsules), reduced pain and improved overall quality of sleep in patients with chronic, moderate-to-severe osteoarthritis (OA) pain compared to placebo, according to a Phase III study published in The Journal of Pain and Symptom Management (Vol. 23, No. 4, 2002).
Once-daily AVINZA was approved in March 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. Ligand plans to launch AVINZA this quarter.
In the article, researchers describe a randomized, four-week study evaluating the safety and efficacy of AVINZA, MS Contin(R) (MSC, morphine sulfate controlled-release, Purdue Frederick), and placebo in 295 patients with chronic, moderate-to-severe OA pain. Patients had failed to achieve adequate response to NSAIDs and acetaminophen or had previously received opioid therapy. Patients were given AVINZA 30 mg. once daily in the morning (QAM) or evening (QPM), MSC 15 mg. twice daily, or placebo. No dosage adjustments were allowed.
According to the WOMAC OA Index Pain Visual Analogue Scale, AVINZA QAM (17% scale improvement), QPM (20%) and MSC twice-daily (18%) demonstrated a statistically significant reduction in pain from baseline over the four-week study compared to placebo (4%). Less pain was reported in all treatment groups by week one, and further reductions in pain were evident throughout the four-week period compared to baseline. Analgesic efficacy was comparable between once-daily AVINZA and twice-daily MSC. According to Overall Arthritis Pain Intensity Scores, AVINZA QAM (26% improvement), QPM (22%) and MSC twice-daily (22%) reduced pain compared to placebo (14%), although these differences were not statistically significant.
AVINZA and MSC also provided improvements in all sleep measures compared to placebo. In addition, AVINZA QAM demonstrated a statistically significant improvement in overall quality of sleep compared to twice-daily MSC at weeks one and four. Sleep disturbances occur in 50-70% of patients with chronic pain. The investigators evaluated overall quality of sleep, need for sleep medication, hours of sleep, difficulty falling asleep, and awakening in the morning and evening due to pain.
"Poor sleep may lead to increased pain, physical disability, and psychological disturbances that accompany chronic pain," said lead author Jacques Caldwell, M.D., of Radiant Research in Daytona Beach, Fla. "In this study, the greatest improvements in sleep measures were experienced by patients taking AVINZA QAM, and further studies are warranted."
Adverse events, most commonly nausea and constipation, were consistent with those commonly observed with opioid therapy and generally similar among the active treatments. A total of 58 patients (20%) withdrew from the study due to adverse events. Six patients experienced a serious adverse event but only one, who was hospitalized for constipation, experienced an adverse event possibly related to study drug (AVINZA QPM).
Open-Label, 26-Week Extension Study of AVINZA
Patients who completed the four-week trial were eligible to participate in an open-label, 26-week extension study of AVINZA QAM or QPM. Of 184 eligible patients, 181 chose to participate in the extension study, during which patients could increase their dose to optimize pain control. Eighty-six patients completed the extension study; of these, 42 (49%) remained on the initial 30 mg. dose of AVINZA. "Nearly half of patients who completed the extension trial remained on the initial once-daily dose, which suggests this modest amount of morphine was adequate for many patients for controlling OA pain over 30 weeks," Dr. Caldwell said.
Improvements in pain intensity, stiffness and physical functioning were observed in the first week of the extension trial and were sustained in all subsequent weeks. Mean clinical improvements through week 12 corresponded with increases in the mean daily dose of AVINZA. In weeks 12 through 30, pain intensity, physical function and stiffness remained stable, as did the average daily dose of AVINZA (approximately 50 mg). "Stable analgesia was observed in the open-label trial, which was consistent with the relatively stable AVINZA dose following dose titration to achieve optimal pain control," Dr. Caldwell said. "This suggests that tolerance was not experienced by the majority of patients in this study."
Adverse events were similar in the QAM and QPM groups, with constipation and nausea the most frequently reported. Of the 181 patients randomized, 56 (31%) withdrew from the study due to adverse events. Four patients experienced serious adverse events that were considered possibly related to AVINZA: enteritis and gastritis; dehydration, diarrhea, hyponatremia, nausea and vomiting; constipation; and vomiting, respectively. All four patients recovered.
Other Recent AVINZA Publications
Recently published articles on AVINZA (formerly Morphelan(TM)) include:
Russell K. Portenoy, M.D., et al, "Steady-State Pharmacokinetic Comparison of a New Extended-Release, Once-Daily Morphine Formulation, AVINZA(TM), and a Twice-Daily Controlled-Release Morphine Formulation in Patients with Chronic Moderate-to-Severe Pain," Journal of Pain and Symptom Management, Vol. 23, No. 4, 2002.
Lise Eliot, Ph.D., et al, "Pharmacokinetic Evaluation of a Sprinkle-Dose Regimen of a Once-Daily, Extended-Release Morphine Formulation," Clinical Therapeutics, Vol. 24, No. 2, February 2002.
Lise Eliot, Ph.D., et al, "Steady-state pharmacokinetic comparison of a new once-daily, extended-release morphine formulation (Morphelan(TM)) and OxyContin(R) twice daily," Journal of Oncology Pharmacy Practice, Vol. 7, 2001.
Lise Eliot, Ph.D., et al, "Evaluation of Two Loading-Dose Regimens of Morphelan(TM) in Healthy Volunteers," The Journal Of Applied Research, Vol. 2, No. 1, Winter 2002.
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).
Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm (http://www.businesswire.com/cnn/lgnd.htm).
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 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 (http://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.
--30--jf/sd* dw/sd
CONTACT: Ligand Pharmaceuticals Incorporated, San Diego
Michael Watts, Director, Investor Relations and
Corporate Communications
858/550-7850
mwatts@ligand.com
KEYWORD: CALIFORNIA
INDUSTRY KEYWORD: BIOTECHNOLOGY MEDICAL PHARMACEUTICAL PRODUCT
SOURCE: Ligand Pharmaceuticals Incorporated
Today's News On The Net - Business Wire's full file on the Internet
with Hyperlinks to your home page.
URL: http://www.businesswire.com
05/01/2002 19:19 EASTERN