User login
LOS ANGELES – Two different monoclonal antibodies showed potent activity for safely cutting blood levels of low-density lipoprotein cholesterol in results from five phase II studies reported at the annual scientific sessions of the American Heart Association.
The findings showed that at the highest dosages tested, both antibodies roughly matched the LDL cholesterol lowering achieved by the highest approved dosages of potent statins, and the antibodies’ effects appeared additive to those of statins when physicians prescribed the two classes in tandem. Because they are antibodies, the new agents are administered by subcutaneous injection or intravenous infusion every 2 or 4 weeks.
While phase III trial results and Food and Drug Administration consideration are a few years down the road, many physicians were buoyed by the prospect of soon being able to treat selected patients with a second 50% reduction in LDL on top of the first 50% drop delivered by statins. Treatment with one of the new antibodies, directed against the plasma protein convertase subtilisin/kexin type 9 (PCSK9) that reduces LDL cell-receptor numbers, leads to increased receptor levels that can halve LDL levels.
Antibodies that inhibit PCSK9 offer a "new paradigm for reducing LDL cholesterol," said Dr. Robert P. Giugliano, who reported data from the largest of the four trials that treated 474 patients with subcutaneous injection of the Amgen 145 antibody either every 2 or 4 weeks.
"We are witnessing the birth of a new treatment. Never have I seen the goal attainments in the lipid area" shown by some of the reports, commented Dr. John J.P. Kastelein, professor and chair of the department of vascular medicine at the Academic Medical Center in Amsterdam. In the results reported by Dr. Giugliano, for example, 90% of patients who received the highest tested antibody dosage every 2 weeks reached their LDL cholesterol goal of less than 70 mg/dL.
Four of the five studies reported at the meeting involved the Amgen 145 antibody:
• The largest of the trials, LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined with Statin Therapy), treated 631 patients who had LDL cholesterol levels of at least 85 mg/dL despite being on a stable statin regimen that for some patients also included ezetimibe. Patients received one of three subcutaneous dosages of Amgen 145 or placebo either every 2 or 4 weeks for 12 weeks. The study’s primary end point was the percent change in LDL cholesterol during 12 weeks on treatment. Among the 78 patients who received the largest antibody dosage every 2 weeks, average LDL levels fell by 66%, reported Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
None of the 474 total patients who received the Amgen 145 antibody stopped receiving the drug because of a serious adverse event. Four of the 474 patients had a creatine kinase elevation greater than five times the upper limit of normal. None had a liver enzyme elevation greater than three times the upper limit of normal. Results from the study were published online concurrent with Dr. Giugliano’s report at the meeting (Lancer 2012;380 [doi: 10.1016/S0140-6736(12)61770-X]).
• A second trial with the same antibody, MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels), enrolled 411 people who were not on any other lipid-lowering medication and who did not have clinical conditions that mandated lipid-reduction treatment so that the impact of the antibody could be assessed in isolation. The highest antibody dosage tested, 140 mg administered subcutaneously every 2 weeks (the same as the highest dosage tested in LAPLACE-TIMI 57), produced an average 51% reduction in LDL cholesterol during 12 weeks of treatment, reported Dr. Michael J. Koren, chief executive officer of the Jacksonville (Fla.) Center for Clinical Research. Among all the dosages tested, administered either every 2 or 4 weeks, average LDL cholesterol levels fell by at least 39%.
None of the antibody-treated patients had a treatment-related adverse event that led to drug discontinuation. Four patients among the 271 who received the antibody had a creatine kinase elevation more than five times the upper limit of normal, as did 2 of the 90 patients who received placebo. Results from the study were published online concurrent with Dr. Koren’s report at the meeting (Lancet 2012;380 [doi: 10.1016/S0140-6736(12)61771-1]).
• A third study of the Amgen 145 antibody, RUTHERFORD (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder), enrolled 167 patients with heterozygous familial hypercholesterolemia who had LDL cholesterol levels of at least 100 mg/dL despite a stable lipid-lowering regimen. The highest dosage of the antibody tested, 420 mg delivered subcutaneously every 4 weeks, led to an average 55% reduction in LDL cholesterol during 12 weeks of treatment in 56 patients, reported Dr. Frederick Raal, head of the division of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. Two-thirds of the patients who received this tested dosage achieved an LDL cholesterol level of less than 70 mg/dL.
Two patients treated with the highest dosage had serious adverse events, compared with none of the 56 placebo-treated patients. Four of the patients on the highest dosage had muscle-related adverse events, compared with two of the placebo patients. In addition, two patients in the highest-dosage group had a creatine kinase elevation greater than five times the upper limit of normal, compared with none of the placebo patients. Results from the study were published online concurrent with Dr. Raal’s report (Circulation 2012;126:2408-17).
• The fourth Amgen 145 study, GAUSS (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects), enrolled 157 patients at cardiovascular risk who were unable to tolerate effective statin doses because of muscle-related adverse effects. The highest dosage of the antibody administered alone tested, 420 mg given subcutaneously every 4 weeks, lowered LDL cholesterol by an average of 51% in 31 patients, reported Dr. Evan A. Stein, director of the Metabolic and Atherosclerosis Research Center in Cincinnati. Among 29 patients who received the same antibody dosage plus 10 mg of ezetimibe daily, average LDL cholesterol fell by 63%.
Three patients who received the antibody stopped treatment because of an adverse effect, compared with two placebo patients. Two of the patients on antibody treatment had creatine kinase elevations greater than 10 times the upper limit of normal. Results from the study were published online concurrent with Dr. Stein’s report (JAMA 2012;308 [doi: 10.1001/jama.2012.25790]).
• The fifth phase II study report at the meeting dealt with an antibody under development by Pfizer, RN316. That study enrolled 135 patients with primary hypercholesterolemia who were not at their goal LDL cholesterol level despite high- or maximal-dosage statin regimens. Patients received one of four dosages of the antibody or placebo as an intravenous infusion every 4 weeks. After 12 weeks of treatment, patients on the highest tested dosage had an average 60% reduction in their LDL cholesterol level, reported Dr. Barry Gumbiner, an endocrinologist and executive director of clinical research for Pfizer in South San Francisco, Calif.
Three patients who received RN316 had a serious adverse event, and one patient stopped the study medication because of an adverse event. Five patients who received the antibody developed myalgia, and one patient had a significant rise in creatinine kinase to greater than 10 times the upper limit of normal. No patients had a clinically significant rise in liver enzymes.
The Amgen 145 studies were sponsored by Amgen. The RN316 study was sponsored by Pfizer. Dr. Giugliano said that he has been a consultant to Amgen. Dr. Koren said that he has received research grants from Amgen. Dr. Raal said that he has received research funding from Amgen and Sanofi. Dr. Stein said that he has been a consultant to Amgen, Adnexus Therapeutics, and Sanofi, and that he has received research support from Amgen, Sanofi, and Regeneron. Dr. Gumbiner said that he is an employee of Pfizer.
In these studies, the antibodies showed quite good lipid-lowering effects and quite good safety. They seemed as potent as moderate- to high-potency statins. Some of the antibodies also lower lipoprotein(a), an added plus.
Medicine has been bumping up against statin intolerance in typical post–myocardial infarction patients. We have aggressive LDL cholesterol goals for these patients, and we get frustrated that we often can’t get them to their goal level. We need to do better for patients at moderate and high cardiovascular disease risk.
 |
Mitchel L. Zoler/IMNG Medical Media
|
High-potency statins reduce LDL cholesterol by about 50%, which leaves room for improvement, plus not every patient does well on a statin. Some patients have myalgia or a liver-function abnormality; roughly 5%-15% of patients prescribed a statin are unable to take the most appropriate dose because of an adverse effect. We have a clear need for different and better ways to lower LDL cholesterol.
The other major target for a new LDL-lowering drug is patients with heterozygous familial hypercholesterolemia. About 500,000-1,000,000 of these patients are American, with a worldwide prevalence of about 10 million. More than half of these patients don’t know they have the disease. Because they start with very high LDL levels, conventional treatment with a potent statin and ezetimibe often does not provide enough LDL reduction.
The phase II results indicate that the antibodies produced a low rate of myalgias. A few patients had large creatinine kinase elevations, and this effect needs further assessment in larger studies, plus more scrutiny is needed of immunologic effects and triggering of antibody reactions to the administered antibody protein. And the impact of treatment with these antibodies needs testing in large studies with cardiovascular disease end points. But so far the results are extremely encouraging for effective lowering of LDL cholesterol, non-HDL cholesterol, and apoprotein B.
Peter W.F. Wilson, M.D., is a professor of medicine in the Clinical Cardiovascular Research Institute of Emory University in Atlanta. Dr. Wilson said that he had no relevant disclosures. He made these comments as the invited discussant, and in an interview.
In these studies, the antibodies showed quite good lipid-lowering effects and quite good safety. They seemed as potent as moderate- to high-potency statins. Some of the antibodies also lower lipoprotein(a), an added plus.
Medicine has been bumping up against statin intolerance in typical post–myocardial infarction patients. We have aggressive LDL cholesterol goals for these patients, and we get frustrated that we often can’t get them to their goal level. We need to do better for patients at moderate and high cardiovascular disease risk.
|
Mitchel L. Zoler/IMNG Medical Media
|
High-potency statins reduce LDL cholesterol by about 50%, which leaves room for improvement, plus not every patient does well on a statin. Some patients have myalgia or a liver-function abnormality; roughly 5%-15% of patients prescribed a statin are unable to take the most appropriate dose because of an adverse effect. We have a clear need for different and better ways to lower LDL cholesterol.
The other major target for a new LDL-lowering drug is patients with heterozygous familial hypercholesterolemia. About 500,000-1,000,000 of these patients are American, with a worldwide prevalence of about 10 million. More than half of these patients don’t know they have the disease. Because they start with very high LDL levels, conventional treatment with a potent statin and ezetimibe often does not provide enough LDL reduction.
The phase II results indicate that the antibodies produced a low rate of myalgias. A few patients had large creatinine kinase elevations, and this effect needs further assessment in larger studies, plus more scrutiny is needed of immunologic effects and triggering of antibody reactions to the administered antibody protein. And the impact of treatment with these antibodies needs testing in large studies with cardiovascular disease end points. But so far the results are extremely encouraging for effective lowering of LDL cholesterol, non-HDL cholesterol, and apoprotein B.
Peter W.F. Wilson, M.D., is a professor of medicine in the Clinical Cardiovascular Research Institute of Emory University in Atlanta. Dr. Wilson said that he had no relevant disclosures. He made these comments as the invited discussant, and in an interview.
In these studies, the antibodies showed quite good lipid-lowering effects and quite good safety. They seemed as potent as moderate- to high-potency statins. Some of the antibodies also lower lipoprotein(a), an added plus.
Medicine has been bumping up against statin intolerance in typical post–myocardial infarction patients. We have aggressive LDL cholesterol goals for these patients, and we get frustrated that we often can’t get them to their goal level. We need to do better for patients at moderate and high cardiovascular disease risk.
|
Mitchel L. Zoler/IMNG Medical Media
|
High-potency statins reduce LDL cholesterol by about 50%, which leaves room for improvement, plus not every patient does well on a statin. Some patients have myalgia or a liver-function abnormality; roughly 5%-15% of patients prescribed a statin are unable to take the most appropriate dose because of an adverse effect. We have a clear need for different and better ways to lower LDL cholesterol.
The other major target for a new LDL-lowering drug is patients with heterozygous familial hypercholesterolemia. About 500,000-1,000,000 of these patients are American, with a worldwide prevalence of about 10 million. More than half of these patients don’t know they have the disease. Because they start with very high LDL levels, conventional treatment with a potent statin and ezetimibe often does not provide enough LDL reduction.
The phase II results indicate that the antibodies produced a low rate of myalgias. A few patients had large creatinine kinase elevations, and this effect needs further assessment in larger studies, plus more scrutiny is needed of immunologic effects and triggering of antibody reactions to the administered antibody protein. And the impact of treatment with these antibodies needs testing in large studies with cardiovascular disease end points. But so far the results are extremely encouraging for effective lowering of LDL cholesterol, non-HDL cholesterol, and apoprotein B.
Peter W.F. Wilson, M.D., is a professor of medicine in the Clinical Cardiovascular Research Institute of Emory University in Atlanta. Dr. Wilson said that he had no relevant disclosures. He made these comments as the invited discussant, and in an interview.
LOS ANGELES – Two different monoclonal antibodies showed potent activity for safely cutting blood levels of low-density lipoprotein cholesterol in results from five phase II studies reported at the annual scientific sessions of the American Heart Association.
The findings showed that at the highest dosages tested, both antibodies roughly matched the LDL cholesterol lowering achieved by the highest approved dosages of potent statins, and the antibodies’ effects appeared additive to those of statins when physicians prescribed the two classes in tandem. Because they are antibodies, the new agents are administered by subcutaneous injection or intravenous infusion every 2 or 4 weeks.
While phase III trial results and Food and Drug Administration consideration are a few years down the road, many physicians were buoyed by the prospect of soon being able to treat selected patients with a second 50% reduction in LDL on top of the first 50% drop delivered by statins. Treatment with one of the new antibodies, directed against the plasma protein convertase subtilisin/kexin type 9 (PCSK9) that reduces LDL cell-receptor numbers, leads to increased receptor levels that can halve LDL levels.
Antibodies that inhibit PCSK9 offer a "new paradigm for reducing LDL cholesterol," said Dr. Robert P. Giugliano, who reported data from the largest of the four trials that treated 474 patients with subcutaneous injection of the Amgen 145 antibody either every 2 or 4 weeks.
"We are witnessing the birth of a new treatment. Never have I seen the goal attainments in the lipid area" shown by some of the reports, commented Dr. John J.P. Kastelein, professor and chair of the department of vascular medicine at the Academic Medical Center in Amsterdam. In the results reported by Dr. Giugliano, for example, 90% of patients who received the highest tested antibody dosage every 2 weeks reached their LDL cholesterol goal of less than 70 mg/dL.
Four of the five studies reported at the meeting involved the Amgen 145 antibody:
• The largest of the trials, LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined with Statin Therapy), treated 631 patients who had LDL cholesterol levels of at least 85 mg/dL despite being on a stable statin regimen that for some patients also included ezetimibe. Patients received one of three subcutaneous dosages of Amgen 145 or placebo either every 2 or 4 weeks for 12 weeks. The study’s primary end point was the percent change in LDL cholesterol during 12 weeks on treatment. Among the 78 patients who received the largest antibody dosage every 2 weeks, average LDL levels fell by 66%, reported Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
None of the 474 total patients who received the Amgen 145 antibody stopped receiving the drug because of a serious adverse event. Four of the 474 patients had a creatine kinase elevation greater than five times the upper limit of normal. None had a liver enzyme elevation greater than three times the upper limit of normal. Results from the study were published online concurrent with Dr. Giugliano’s report at the meeting (Lancer 2012;380 [doi: 10.1016/S0140-6736(12)61770-X]).
• A second trial with the same antibody, MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels), enrolled 411 people who were not on any other lipid-lowering medication and who did not have clinical conditions that mandated lipid-reduction treatment so that the impact of the antibody could be assessed in isolation. The highest antibody dosage tested, 140 mg administered subcutaneously every 2 weeks (the same as the highest dosage tested in LAPLACE-TIMI 57), produced an average 51% reduction in LDL cholesterol during 12 weeks of treatment, reported Dr. Michael J. Koren, chief executive officer of the Jacksonville (Fla.) Center for Clinical Research. Among all the dosages tested, administered either every 2 or 4 weeks, average LDL cholesterol levels fell by at least 39%.
None of the antibody-treated patients had a treatment-related adverse event that led to drug discontinuation. Four patients among the 271 who received the antibody had a creatine kinase elevation more than five times the upper limit of normal, as did 2 of the 90 patients who received placebo. Results from the study were published online concurrent with Dr. Koren’s report at the meeting (Lancet 2012;380 [doi: 10.1016/S0140-6736(12)61771-1]).
• A third study of the Amgen 145 antibody, RUTHERFORD (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder), enrolled 167 patients with heterozygous familial hypercholesterolemia who had LDL cholesterol levels of at least 100 mg/dL despite a stable lipid-lowering regimen. The highest dosage of the antibody tested, 420 mg delivered subcutaneously every 4 weeks, led to an average 55% reduction in LDL cholesterol during 12 weeks of treatment in 56 patients, reported Dr. Frederick Raal, head of the division of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. Two-thirds of the patients who received this tested dosage achieved an LDL cholesterol level of less than 70 mg/dL.
Two patients treated with the highest dosage had serious adverse events, compared with none of the 56 placebo-treated patients. Four of the patients on the highest dosage had muscle-related adverse events, compared with two of the placebo patients. In addition, two patients in the highest-dosage group had a creatine kinase elevation greater than five times the upper limit of normal, compared with none of the placebo patients. Results from the study were published online concurrent with Dr. Raal’s report (Circulation 2012;126:2408-17).
• The fourth Amgen 145 study, GAUSS (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects), enrolled 157 patients at cardiovascular risk who were unable to tolerate effective statin doses because of muscle-related adverse effects. The highest dosage of the antibody administered alone tested, 420 mg given subcutaneously every 4 weeks, lowered LDL cholesterol by an average of 51% in 31 patients, reported Dr. Evan A. Stein, director of the Metabolic and Atherosclerosis Research Center in Cincinnati. Among 29 patients who received the same antibody dosage plus 10 mg of ezetimibe daily, average LDL cholesterol fell by 63%.
Three patients who received the antibody stopped treatment because of an adverse effect, compared with two placebo patients. Two of the patients on antibody treatment had creatine kinase elevations greater than 10 times the upper limit of normal. Results from the study were published online concurrent with Dr. Stein’s report (JAMA 2012;308 [doi: 10.1001/jama.2012.25790]).
• The fifth phase II study report at the meeting dealt with an antibody under development by Pfizer, RN316. That study enrolled 135 patients with primary hypercholesterolemia who were not at their goal LDL cholesterol level despite high- or maximal-dosage statin regimens. Patients received one of four dosages of the antibody or placebo as an intravenous infusion every 4 weeks. After 12 weeks of treatment, patients on the highest tested dosage had an average 60% reduction in their LDL cholesterol level, reported Dr. Barry Gumbiner, an endocrinologist and executive director of clinical research for Pfizer in South San Francisco, Calif.
Three patients who received RN316 had a serious adverse event, and one patient stopped the study medication because of an adverse event. Five patients who received the antibody developed myalgia, and one patient had a significant rise in creatinine kinase to greater than 10 times the upper limit of normal. No patients had a clinically significant rise in liver enzymes.
The Amgen 145 studies were sponsored by Amgen. The RN316 study was sponsored by Pfizer. Dr. Giugliano said that he has been a consultant to Amgen. Dr. Koren said that he has received research grants from Amgen. Dr. Raal said that he has received research funding from Amgen and Sanofi. Dr. Stein said that he has been a consultant to Amgen, Adnexus Therapeutics, and Sanofi, and that he has received research support from Amgen, Sanofi, and Regeneron. Dr. Gumbiner said that he is an employee of Pfizer.
LOS ANGELES – Two different monoclonal antibodies showed potent activity for safely cutting blood levels of low-density lipoprotein cholesterol in results from five phase II studies reported at the annual scientific sessions of the American Heart Association.
The findings showed that at the highest dosages tested, both antibodies roughly matched the LDL cholesterol lowering achieved by the highest approved dosages of potent statins, and the antibodies’ effects appeared additive to those of statins when physicians prescribed the two classes in tandem. Because they are antibodies, the new agents are administered by subcutaneous injection or intravenous infusion every 2 or 4 weeks.
While phase III trial results and Food and Drug Administration consideration are a few years down the road, many physicians were buoyed by the prospect of soon being able to treat selected patients with a second 50% reduction in LDL on top of the first 50% drop delivered by statins. Treatment with one of the new antibodies, directed against the plasma protein convertase subtilisin/kexin type 9 (PCSK9) that reduces LDL cell-receptor numbers, leads to increased receptor levels that can halve LDL levels.
Antibodies that inhibit PCSK9 offer a "new paradigm for reducing LDL cholesterol," said Dr. Robert P. Giugliano, who reported data from the largest of the four trials that treated 474 patients with subcutaneous injection of the Amgen 145 antibody either every 2 or 4 weeks.
"We are witnessing the birth of a new treatment. Never have I seen the goal attainments in the lipid area" shown by some of the reports, commented Dr. John J.P. Kastelein, professor and chair of the department of vascular medicine at the Academic Medical Center in Amsterdam. In the results reported by Dr. Giugliano, for example, 90% of patients who received the highest tested antibody dosage every 2 weeks reached their LDL cholesterol goal of less than 70 mg/dL.
Four of the five studies reported at the meeting involved the Amgen 145 antibody:
• The largest of the trials, LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined with Statin Therapy), treated 631 patients who had LDL cholesterol levels of at least 85 mg/dL despite being on a stable statin regimen that for some patients also included ezetimibe. Patients received one of three subcutaneous dosages of Amgen 145 or placebo either every 2 or 4 weeks for 12 weeks. The study’s primary end point was the percent change in LDL cholesterol during 12 weeks on treatment. Among the 78 patients who received the largest antibody dosage every 2 weeks, average LDL levels fell by 66%, reported Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
None of the 474 total patients who received the Amgen 145 antibody stopped receiving the drug because of a serious adverse event. Four of the 474 patients had a creatine kinase elevation greater than five times the upper limit of normal. None had a liver enzyme elevation greater than three times the upper limit of normal. Results from the study were published online concurrent with Dr. Giugliano’s report at the meeting (Lancer 2012;380 [doi: 10.1016/S0140-6736(12)61770-X]).
• A second trial with the same antibody, MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels), enrolled 411 people who were not on any other lipid-lowering medication and who did not have clinical conditions that mandated lipid-reduction treatment so that the impact of the antibody could be assessed in isolation. The highest antibody dosage tested, 140 mg administered subcutaneously every 2 weeks (the same as the highest dosage tested in LAPLACE-TIMI 57), produced an average 51% reduction in LDL cholesterol during 12 weeks of treatment, reported Dr. Michael J. Koren, chief executive officer of the Jacksonville (Fla.) Center for Clinical Research. Among all the dosages tested, administered either every 2 or 4 weeks, average LDL cholesterol levels fell by at least 39%.
None of the antibody-treated patients had a treatment-related adverse event that led to drug discontinuation. Four patients among the 271 who received the antibody had a creatine kinase elevation more than five times the upper limit of normal, as did 2 of the 90 patients who received placebo. Results from the study were published online concurrent with Dr. Koren’s report at the meeting (Lancet 2012;380 [doi: 10.1016/S0140-6736(12)61771-1]).
• A third study of the Amgen 145 antibody, RUTHERFORD (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder), enrolled 167 patients with heterozygous familial hypercholesterolemia who had LDL cholesterol levels of at least 100 mg/dL despite a stable lipid-lowering regimen. The highest dosage of the antibody tested, 420 mg delivered subcutaneously every 4 weeks, led to an average 55% reduction in LDL cholesterol during 12 weeks of treatment in 56 patients, reported Dr. Frederick Raal, head of the division of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. Two-thirds of the patients who received this tested dosage achieved an LDL cholesterol level of less than 70 mg/dL.
Two patients treated with the highest dosage had serious adverse events, compared with none of the 56 placebo-treated patients. Four of the patients on the highest dosage had muscle-related adverse events, compared with two of the placebo patients. In addition, two patients in the highest-dosage group had a creatine kinase elevation greater than five times the upper limit of normal, compared with none of the placebo patients. Results from the study were published online concurrent with Dr. Raal’s report (Circulation 2012;126:2408-17).
• The fourth Amgen 145 study, GAUSS (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects), enrolled 157 patients at cardiovascular risk who were unable to tolerate effective statin doses because of muscle-related adverse effects. The highest dosage of the antibody administered alone tested, 420 mg given subcutaneously every 4 weeks, lowered LDL cholesterol by an average of 51% in 31 patients, reported Dr. Evan A. Stein, director of the Metabolic and Atherosclerosis Research Center in Cincinnati. Among 29 patients who received the same antibody dosage plus 10 mg of ezetimibe daily, average LDL cholesterol fell by 63%.
Three patients who received the antibody stopped treatment because of an adverse effect, compared with two placebo patients. Two of the patients on antibody treatment had creatine kinase elevations greater than 10 times the upper limit of normal. Results from the study were published online concurrent with Dr. Stein’s report (JAMA 2012;308 [doi: 10.1001/jama.2012.25790]).
• The fifth phase II study report at the meeting dealt with an antibody under development by Pfizer, RN316. That study enrolled 135 patients with primary hypercholesterolemia who were not at their goal LDL cholesterol level despite high- or maximal-dosage statin regimens. Patients received one of four dosages of the antibody or placebo as an intravenous infusion every 4 weeks. After 12 weeks of treatment, patients on the highest tested dosage had an average 60% reduction in their LDL cholesterol level, reported Dr. Barry Gumbiner, an endocrinologist and executive director of clinical research for Pfizer in South San Francisco, Calif.
Three patients who received RN316 had a serious adverse event, and one patient stopped the study medication because of an adverse event. Five patients who received the antibody developed myalgia, and one patient had a significant rise in creatinine kinase to greater than 10 times the upper limit of normal. No patients had a clinically significant rise in liver enzymes.
The Amgen 145 studies were sponsored by Amgen. The RN316 study was sponsored by Pfizer. Dr. Giugliano said that he has been a consultant to Amgen. Dr. Koren said that he has received research grants from Amgen. Dr. Raal said that he has received research funding from Amgen and Sanofi. Dr. Stein said that he has been a consultant to Amgen, Adnexus Therapeutics, and Sanofi, and that he has received research support from Amgen, Sanofi, and Regeneron. Dr. Gumbiner said that he is an employee of Pfizer.
AT THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Patients on the largest Amgen 145 dosage had an average 66% reduction in their LDL cholesterol, and 90% reached their goal LDL level.
Data Source: This was a phase II randomized study of Amgen 145 antibody in 631 patients not at their goal cholesterol level despite a stable statin regimen.
Disclosures: The Amgen 145 studies were sponsored by Amgen. The RN316 study was sponsored by Pfizer. Dr. Giugliano said that he has been a consultant to Amgen. Dr. Koren said that he has received research grants from Amgen. Dr. Raal said that he has received research funding from Amgen and Sanofi. Dr. Stein said that he has been a consultant to Amgen, Adnexus Therapeutics, and Sanofi, and that he has received research support from Amgen, Sanofi, and Regeneron. Dr. Gumbiner said that he is an employee of Pfizer.
