User login
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Treatment with evolocumab every 4 weeks for 1 year safely cut average LDL cholesterol levels by 50%, compared with controls.
Data source: OSLER, an open-label study that randomized 368 patients to standard care and 736 to standard care plus evolocumab treatment.
Disclosures: OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
