RandyW Posted June 6, 2006 Share Posted June 6, 2006 New Data on LunNew Data on Lung Cancer Trials with Targretin® is Presented at ASCO; Biomarker Data Analysis Supports Benefit in Subsets of Patients in 1st and 3rd Line NSCLC 6/5/2006 8:30:00 AM EST BIOWIRE Ligand Pharmaceuticals Incorporated (Pink Sheets:LGND) (the "Company" or "Ligand") -- Results of retrospective analysis in large trials in first line NSCLC and final analysis of a 3rd line NSCLC trial were presented Sunday, June 4th at the annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. Lung cancer data presented yesterday include: -- A retrospective analysis of SPIRIT I and II phase III trials describing components of Metabolic Syndrome in patients benefiting from Targretin®. -- Biomarker identification and correlation with prolonged survival in a subset of NSCLC patients in SPIRIT I and II. -- Final data analysis of a large phase II trial with Targretin monotherapy in 3rd line NSCLC. -- A preclinical study on Targretin prevention or reversal of gemcitabine resistance in NSCLC. "Collectively, the results presented at ASCO this year further strengthen, with the use of selective biomarker analysis, the potential benefit of Targretin therapy added to chemotherapy in a first line setting, or as monotherapy in third line, heavily pretreated patients, in an important group of NSCLC patients," said Andres Negro-Vilar, Executive Vice President, R&D and Chief Scientific Officer, Ligand Pharmaceuticals. "The identified patients in the subgroups most benefiting from Targretin (males, smokers, greater weight loss, stage IV disease) are among those with the poorest prognosis and have not been shown so far to derive benefit from other targeted therapies. Collectively, identification and characterization of a predictive biomarker in these studies has been instrumental to define a prospective pathway to confirm the utility and seek registration for Targretin capsules in first and third line NSCLC." Retrospective analysis of SPIRIT I and II trials shows that baseline Metabolic Syndrome risk factors are associated with high sensitivity to Targretin and prolonged survival A poster presented by lead author Z. Dziewanowska, Vice President, Clinical Research at Ligand Pharmaceuticals conducted a retrospective pooled analysis of 1,213 patients in SPIRIT I and II phase III trials to evaluate the presence of biomarker correlates of prolonged survival. High sensitivity to Targretin, as defined by high increases in triglycerides (34% of patients, N=194) resulted in a statistically significant (P=0.003) better median survival of 12.4 months vs. 9.5 months in the pooled chemo control group (N=618). Further analysis of these subpopulations of high responders was conducted to identify their demographics and other baseline risk factors that may contribute to their different sensitivity to Targretin. Patients with particularly prolonged survival in this subgroup include males, smokers, stage IV disease and patients with greater weight loss prior to treatment, all risk factors associated with worst prognosis in NSCLC. An evaluation of metabolic syndrome risk factors showed that the Targretin-sensitive subgroup showing better survival had at baseline a significant (p less than 0.001) cluster of risk factors associated with Metabolic Syndrome, i.e., greater body mass index, higher total cholesterol/HDL ratio, higher total cholesterol and triglycerides and higher uric acid, than either control group patients or those Targretin patients with no/low triglyceride elevations. All these parameters analyzed during treatment also showed similar statistical correlations (p less than 0.001) either individually or as part of a composite risk score analysis. The report concludes that baseline and in-treatment triglycerides and key Metabolic Syndrome risk factors are important biomarker predictors of the beneficial survival impact of Targretin in first-line NSCLC. Biomarker correlates of survival in NSCLC: Role of RXR-Beta and associated receptors in mediating Targretin impact on patient survival in first-line NSCLC A study presented by Andres Negro-Vilar, Executive Vice President of R&D at Ligand Pharmaceuticals described the results of the analysis of lung tumor biopsies from a subset of patients in the SPIRIT I and II phase III trials. To further support the biomarker-directed analysis of Targretin benefit in these studies, expression levels of RXR-Beta, other RXR subtypes and associated receptor heterodimers were evaluated in lung tumor biopsies from a subset of patients in both arms (chemo and chemo plus Targretin) of those studies. Results show that those patients with high level of expression of the RXR-Beta receptor (the target for Targretin molecular activity) had a significantly longer survival (p=0.01) of 14.6 months vs. 10.6 months for those patients with low RXR-Beta expression. These results confirm and extend to late stage (stage III B and IV) patients the earlier observations of Brabender et al (Clin. Cancer Res. 2002, 8: 430) identifying RXR-Beta as an individual predictor of survival in NSCLC. The best survival outcome was seen in those patients with high RXR-Beta expression in the tumor receiving Targretin plus chemo treatment (20.9 months median survival) compared with high RXR-Beta plus chemo only treatment (12.1 month median survival). Promising results of Targretin capsules in patients with relapsed non-small-cell lung cancer -- Final results of a large Phase II multicenter trial A poster presentation reported the final results of a Phase II multicenter trial of single-agent Targretin in patients with advanced relapsed/refractory NSCLC who have failed multiple prior therapies. This study, the first to evaluate Targretin in this patient population, enrolled 146 patients at 36 sites. The patients had a median age of 66 years (range, 34 - 87), they had failed a median of 3 prior therapies (range, 2 - 7), all had failed prior chemotherapy, and 55% had failed prior gefitinib therapy. The overall median survival was 5 months and the 1-year survival was 23%. Since many patients had fairly advanced disease and had progressed within days of entry into the study, a 2-week landmarked analysis showed a median and 1-year survival of 6 months and 27%, respectively, in the subset of 126 patients who had received Targretin for at least 2 weeks. Targretin was usually well tolerated. The most common Grade 3-4 side effects were increased serum triglycerides, which was reported in 23% of the patients but was not associated with any clinical symptom, and dyspnea (16%) and fatigue (10%), the latter most likely due to the lung cancer. Other Grade 3-4 adverse events were reported in less than 5% of the patients. The authors further investigated the relationship between Targretin-induced hypertriglyceridemia and survival, which was reported initially in the SPIRIT Phase III trials in patients with previously untreated NSCLC. In the subset of 74 patients (51%) who experienced Grade 1-4 hypertriglyceridemia, the median and 1-year survivals were 6 months and 30%, significantly higher than 3 months and 18%, respectively, in patients with no increased triglycerides (p = 0.004). "We are pleased to have completed this large trial investigating single-agent Targretin as third-line therapy in patients with advanced NSCLC," said Dr. R. Govindan, Associate Professor of Medicine at Washington University School of Medicine in St. Louis, and the lead study author. "Considering that patients enrolled in this trial were heavily pretreated, the overall survival results achieved with Targretin capsules are encouraging." Dr. Govindan continued, "and the association between hypertriglyceridemia and survival is consistent with the observations of the SPIRIT trials and presents an approach to define a subset of NSCLC patients who may benefit even more from Targretin." Targretin prevents and reverses gemcitabine resistance in NSCLC cells A poster by T. Herman, Molecular Oncology Scientist at Ligand, describes the activity of Targretin in preventing or reversing the development of resistance to gemcitabine, a chemo therapeutic agent frequently used in chemo doublets for the treatment of first line NSCLC or as single agent beyond first line. The results show that resistance to gemcitabine is correlated with increased expression of rrm1 (ribonucleotide reductase M1) a gene known to be involved in gemcitabine resistance and that this effect was due to gene amplification at the 11 p 15 locus. Targretin treatment in combination with gemcitabine resulted in reduction/elimination of rrm1 gene amplification and re-sensitization of the cells to the growth suppressive activity of gemcitabine. About Targretin In December 1999, the FDA approved Targretin capsules for the treatment of cutaneous manifestations of cutaneous t-cell lymphoma in patients who are refractory to at least one prior systemic therapy. The European Commission granted marketing authorization for Targretin Capsules in March 2001, and the product is currently marketed in many major European countries, including Germany, the United Kingdom, France and Italy. 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 forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These include statements regarding data analysis and evaluation of Targretin, utility or potential benefits to patients, plans for continued development and further studies of Targretin. Actual events or results may differ from our expectations. For example, there can be no assurance that other studies or evaluations of Targretin will be favorable or that they will confirm results of previous trials, that data evaluation will be completed or demonstrate any hypothesis or endpoint, that Targretin will provide utility or benefits to certain patients, that any presentations will be favorably received, that Targretin will be useful in new indications alone or in combination with other drugs, that marketing applications will be filed or, if filed, approved, nor that further clinical or commercial development of these drugs will be completed or successful. Our stock price may suffer as result of the failure of any trials to be completed or meet their endpoints or if any actual events differ from our expectations. 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. CONTACT: Ligand Pharmaceuticals Incorporated Paul V. Maier, 858-550-7573 g Cancer Trials with Targretin® is Presented at ASCO; Biomarker Data Analysis Supports Benefit in Subsets of Patients in 1st and 3rd Line NSCLC 6/5/2006 8:30:00 AM EST BIOWIRE Ligand Pharmaceuticals Incorporated (Pink Sheets:LGND) (the "Company" or "Ligand") -- Results of retrospective analysis in large trials in first line NSCLC and final analysis of a 3rd line NSCLC trial were presented Sunday, June 4th at the annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. Lung cancer data presented yesterday include: -- A retrospective analysis of SPIRIT I and II phase III trials describing components of Metabolic Syndrome in patients benefiting from Targretin®. -- Biomarker identification and correlation with prolonged survival in a subset of NSCLC patients in SPIRIT I and II. -- Final data analysis of a large phase II trial with Targretin monotherapy in 3rd line NSCLC. -- A preclinical study on Targretin prevention or reversal of gemcitabine resistance in NSCLC. "Collectively, the results presented at ASCO this year further strengthen, with the use of selective biomarker analysis, the potential benefit of Targretin therapy added to chemotherapy in a first line setting, or as monotherapy in third line, heavily pretreated patients, in an important group of NSCLC patients," said Andres Negro-Vilar, Executive Vice President, R&D and Chief Scientific Officer, Ligand Pharmaceuticals. "The identified patients in the subgroups most benefiting from Targretin (males, smokers, greater weight loss, stage IV disease) are among those with the poorest prognosis and have not been shown so far to derive benefit from other targeted therapies. Collectively, identification and characterization of a predictive biomarker in these studies has been instrumental to define a prospective pathway to confirm the utility and seek registration for Targretin capsules in first and third line NSCLC." Retrospective analysis of SPIRIT I and II trials shows that baseline Metabolic Syndrome risk factors are associated with high sensitivity to Targretin and prolonged survival A poster presented by lead author Z. Dziewanowska, Vice President, Clinical Research at Ligand Pharmaceuticals conducted a retrospective pooled analysis of 1,213 patients in SPIRIT I and II phase III trials to evaluate the presence of biomarker correlates of prolonged survival. High sensitivity to Targretin, as defined by high increases in triglycerides (34% of patients, N=194) resulted in a statistically significant (P=0.003) better median survival of 12.4 months vs. 9.5 months in the pooled chemo control group (N=618). Further analysis of these subpopulations of high responders was conducted to identify their demographics and other baseline risk factors that may contribute to their different sensitivity to Targretin. Patients with particularly prolonged survival in this subgroup include males, smokers, stage IV disease and patients with greater weight loss prior to treatment, all risk factors associated with worst prognosis in NSCLC. An evaluation of metabolic syndrome risk factors showed that the Targretin-sensitive subgroup showing better survival had at baseline a significant (p less than 0.001) cluster of risk factors associated with Metabolic Syndrome, i.e., greater body mass index, higher total cholesterol/HDL ratio, higher total cholesterol and triglycerides and higher uric acid, than either control group patients or those Targretin patients with no/low triglyceride elevations. All these parameters analyzed during treatment also showed similar statistical correlations (p less than 0.001) either individually or as part of a composite risk score analysis. The report concludes that baseline and in-treatment triglycerides and key Metabolic Syndrome risk factors are important biomarker predictors of the beneficial survival impact of Targretin in first-line NSCLC. Biomarker correlates of survival in NSCLC: Role of RXR-Beta and associated receptors in mediating Targretin impact on patient survival in first-line NSCLC A study presented by Andres Negro-Vilar, Executive Vice President of R&D at Ligand Pharmaceuticals described the results of the analysis of lung tumor biopsies from a subset of patients in the SPIRIT I and II phase III trials. To further support the biomarker-directed analysis of Targretin benefit in these studies, expression levels of RXR-Beta, other RXR subtypes and associated receptor heterodimers were evaluated in lung tumor biopsies from a subset of patients in both arms (chemo and chemo plus Targretin) of those studies. Results show that those patients with high level of expression of the RXR-Beta receptor (the target for Targretin molecular activity) had a significantly longer survival (p=0.01) of 14.6 months vs. 10.6 months for those patients with low RXR-Beta expression. These results confirm and extend to late stage (stage III B and IV) patients the earlier observations of Brabender et al (Clin. Cancer Res. 2002, 8: 430) identifying RXR-Beta as an individual predictor of survival in NSCLC. The best survival outcome was seen in those patients with high RXR-Beta expression in the tumor receiving Targretin plus chemo treatment (20.9 months median survival) compared with high RXR-Beta plus chemo only treatment (12.1 month median survival). Promising results of Targretin capsules in patients with relapsed non-small-cell lung cancer -- Final results of a large Phase II multicenter trial A poster presentation reported the final results of a Phase II multicenter trial of single-agent Targretin in patients with advanced relapsed/refractory NSCLC who have failed multiple prior therapies. This study, the first to evaluate Targretin in this patient population, enrolled 146 patients at 36 sites. The patients had a median age of 66 years (range, 34 - 87), they had failed a median of 3 prior therapies (range, 2 - 7), all had failed prior chemotherapy, and 55% had failed prior gefitinib therapy. The overall median survival was 5 months and the 1-year survival was 23%. Since many patients had fairly advanced disease and had progressed within days of entry into the study, a 2-week landmarked analysis showed a median and 1-year survival of 6 months and 27%, respectively, in the subset of 126 patients who had received Targretin for at least 2 weeks. Targretin was usually well tolerated. The most common Grade 3-4 side effects were increased serum triglycerides, which was reported in 23% of the patients but was not associated with any clinical symptom, and dyspnea (16%) and fatigue (10%), the latter most likely due to the lung cancer. Other Grade 3-4 adverse events were reported in less than 5% of the patients. The authors further investigated the relationship between Targretin-induced hypertriglyceridemia and survival, which was reported initially in the SPIRIT Phase III trials in patients with previously untreated NSCLC. In the subset of 74 patients (51%) who experienced Grade 1-4 hypertriglyceridemia, the median and 1-year survivals were 6 months and 30%, significantly higher than 3 months and 18%, respectively, in patients with no increased triglycerides (p = 0.004). "We are pleased to have completed this large trial investigating single-agent Targretin as third-line therapy in patients with advanced NSCLC," said Dr. R. Govindan, Associate Professor of Medicine at Washington University School of Medicine in St. Louis, and the lead study author. "Considering that patients enrolled in this trial were heavily pretreated, the overall survival results achieved with Targretin capsules are encouraging." Dr. Govindan continued, "and the association between hypertriglyceridemia and survival is consistent with the observations of the SPIRIT trials and presents an approach to define a subset of NSCLC patients who may benefit even more from Targretin." Targretin prevents and reverses gemcitabine resistance in NSCLC cells A poster by T. Herman, Molecular Oncology Scientist at Ligand, describes the activity of Targretin in preventing or reversing the development of resistance to gemcitabine, a chemo therapeutic agent frequently used in chemo doublets for the treatment of first line NSCLC or as single agent beyond first line. The results show that resistance to gemcitabine is correlated with increased expression of rrm1 (ribonucleotide reductase M1) a gene known to be involved in gemcitabine resistance and that this effect was due to gene amplification at the 11 p 15 locus. Targretin treatment in combination with gemcitabine resulted in reduction/elimination of rrm1 gene amplification and re-sensitization of the cells to the growth suppressive activity of gemcitabine. About Targretin In December 1999, the FDA approved Targretin capsules for the treatment of cutaneous manifestations of cutaneous t-cell lymphoma in patients who are refractory to at least one prior systemic therapy. The European Commission granted marketing authorization for Targretin Capsules in March 2001, and the product is currently marketed in many major European countries, including Germany, the United Kingdom, France and Italy. 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 forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These include statements regarding data analysis and evaluation of Targretin, utility or potential benefits to patients, plans for continued development and further studies of Targretin. Actual events or results may differ from our expectations. For example, there can be no assurance that other studies or evaluations of Targretin will be favorable or that they will confirm results of previous trials, that data evaluation will be completed or demonstrate any hypothesis or endpoint, that Targretin will provide utility or benefits to certain patients, that any presentations will be favorably received, that Targretin will be useful in new indications alone or in combination with other drugs, that marketing applications will be filed or, if filed, approved, nor that further clinical or commercial development of these drugs will be completed or successful. Our stock price may suffer as result of the failure of any trials to be completed or meet their endpoints or if any actual events differ from our expectations. 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. CONTACT: Ligand Pharmaceuticals Incorporated Paul V. Maier, 858-550-7573 Quote Link to comment Share on other sites More sharing options...
tnmynatt Posted June 6, 2006 Share Posted June 6, 2006 Charlie was in this third-line monotherapy study. Unfortunately, he did not respond even though his triglycerides went through the roof. Glad it is working for others. Quote Link to comment Share on other sites More sharing options...
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