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A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.