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The lack of available treatments that adequately treat Parkinson’s disease psychosis proved to be a big motivating factor for a majority of members of the Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee, who voted at a meeting March 29 that the benefits of the novel drug pimavanserin outweigh its risks.
The panel voted 12-2 in support of the benefit-to-risk ratio for pimavanserin, a selective 5-hydroxytryptamine2A (5-HT2A) inverse agonist that does not affect the dopaminergic, histaminergic, adrenergic, or muscarinic systems, according to its developer, Acadia Pharmaceuticals.
Although Acadia submitted just one positive phase III trial out of a total of four 6-week, randomized, placebo-controlled trials of pimavanserin, committee members voted 12-2 that the company “provided substantial evidence of the effectiveness” of the drug for the treatment of psychosis associated with Parkinsons’s disease (PDP). Another 11-3 vote supported the question of whether pimavanersin’s safety profile was “adequately characterized.”
Results from the single phase III trial conducted in 199 patients with Parkinsons’s disease psychosis (PDP) unequivocally showed that 34 mg/day pimavanserin improved scores on an abbreviated, 9-item version of the 20-item Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions score, called the SAPS-PD. After 6 weeks, SAPS-PD scores declined by a statistically significant 3.1 points or 23.1% on active treatment versus placebo, which was an absolute decrease of about 6 points from baseline. One of the questions brought up by FDA reviewers and panelists was whether the 3.1-point difference (on the SAPS-PD’s 45-point scale) seen between active treatment and placebo was of great enough clinical benefit to outweigh the higher rate of serious adverse events observed with pimavanserin versus placebo across all of the 6-week trials.
Across all four 6-week studies, serious adverse events occurred in 16 (7.9%) of 202 patients who took 34 mg pimavanserin and in 8 (3.5%) of 231 placebo-treated patients. Three deaths occurred in the patients who received pimavanserin, and one in the placebo arms. However, none of the deaths were considered to be a drug-related event, and the deaths were not pathologically unique relative to what is expected in the disease course of patients with PDP. The death of another patient who had received 10 mg pimavanserin in an earlier uncontrolled trial also was reported.
Meanwhile, the drug did not worsen motor symptoms of Parkinson’s disease.
FDA analyses showed that 11 patients would need to be treated in order for 1 patient to have a 50% reduction in the SAPS-PD, which corresponds to “much improvement,” whereas 22 patients would need to be treated for 1 to be harmed with a serious adverse event (SAE). This means that for every two patients who have a 50% reduction in the SAPS-PD, one will have a serious adverse event attributable to pimavanserin. Overall, 37.2% of patients in the pimavanserin arm of the phase III trial had a 50% decline in the SAPS-PD after 6 weeks, compared with 27.8% in the placebo arm.
However, the number needed to harm/number needed to treat ratio for SAEs had wide confidence intervals, and there was a high degree of uncertainty about its magnitude such that the inclusion of just one or two more SAEs would substantially change the ratio, many panelists agreed.
Some panelists voiced concern about pimavanserin being called an antipsychotic, even though it has demonstrated no proof of efficacy in conditions with classical symptoms of psychosis, such as schizophrenia, and worried about its off-label use in patients with other conditions who have psychotic symptoms. They also called for a postmarketing observational study to track the safety of the drug if it is approved.
Pimavanserin’s application received breakthrough drug status from the FDA and was fast tracked, and a decision is expected from the agency by May 1. If approved, pimavanserin would be marketed under the trade name Nuplazid.
The lack of available treatments that adequately treat Parkinson’s disease psychosis proved to be a big motivating factor for a majority of members of the Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee, who voted at a meeting March 29 that the benefits of the novel drug pimavanserin outweigh its risks.
The panel voted 12-2 in support of the benefit-to-risk ratio for pimavanserin, a selective 5-hydroxytryptamine2A (5-HT2A) inverse agonist that does not affect the dopaminergic, histaminergic, adrenergic, or muscarinic systems, according to its developer, Acadia Pharmaceuticals.
Although Acadia submitted just one positive phase III trial out of a total of four 6-week, randomized, placebo-controlled trials of pimavanserin, committee members voted 12-2 that the company “provided substantial evidence of the effectiveness” of the drug for the treatment of psychosis associated with Parkinsons’s disease (PDP). Another 11-3 vote supported the question of whether pimavanersin’s safety profile was “adequately characterized.”
Results from the single phase III trial conducted in 199 patients with Parkinsons’s disease psychosis (PDP) unequivocally showed that 34 mg/day pimavanserin improved scores on an abbreviated, 9-item version of the 20-item Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions score, called the SAPS-PD. After 6 weeks, SAPS-PD scores declined by a statistically significant 3.1 points or 23.1% on active treatment versus placebo, which was an absolute decrease of about 6 points from baseline. One of the questions brought up by FDA reviewers and panelists was whether the 3.1-point difference (on the SAPS-PD’s 45-point scale) seen between active treatment and placebo was of great enough clinical benefit to outweigh the higher rate of serious adverse events observed with pimavanserin versus placebo across all of the 6-week trials.
Across all four 6-week studies, serious adverse events occurred in 16 (7.9%) of 202 patients who took 34 mg pimavanserin and in 8 (3.5%) of 231 placebo-treated patients. Three deaths occurred in the patients who received pimavanserin, and one in the placebo arms. However, none of the deaths were considered to be a drug-related event, and the deaths were not pathologically unique relative to what is expected in the disease course of patients with PDP. The death of another patient who had received 10 mg pimavanserin in an earlier uncontrolled trial also was reported.
Meanwhile, the drug did not worsen motor symptoms of Parkinson’s disease.
FDA analyses showed that 11 patients would need to be treated in order for 1 patient to have a 50% reduction in the SAPS-PD, which corresponds to “much improvement,” whereas 22 patients would need to be treated for 1 to be harmed with a serious adverse event (SAE). This means that for every two patients who have a 50% reduction in the SAPS-PD, one will have a serious adverse event attributable to pimavanserin. Overall, 37.2% of patients in the pimavanserin arm of the phase III trial had a 50% decline in the SAPS-PD after 6 weeks, compared with 27.8% in the placebo arm.
However, the number needed to harm/number needed to treat ratio for SAEs had wide confidence intervals, and there was a high degree of uncertainty about its magnitude such that the inclusion of just one or two more SAEs would substantially change the ratio, many panelists agreed.
Some panelists voiced concern about pimavanserin being called an antipsychotic, even though it has demonstrated no proof of efficacy in conditions with classical symptoms of psychosis, such as schizophrenia, and worried about its off-label use in patients with other conditions who have psychotic symptoms. They also called for a postmarketing observational study to track the safety of the drug if it is approved.
Pimavanserin’s application received breakthrough drug status from the FDA and was fast tracked, and a decision is expected from the agency by May 1. If approved, pimavanserin would be marketed under the trade name Nuplazid.
The lack of available treatments that adequately treat Parkinson’s disease psychosis proved to be a big motivating factor for a majority of members of the Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee, who voted at a meeting March 29 that the benefits of the novel drug pimavanserin outweigh its risks.
The panel voted 12-2 in support of the benefit-to-risk ratio for pimavanserin, a selective 5-hydroxytryptamine2A (5-HT2A) inverse agonist that does not affect the dopaminergic, histaminergic, adrenergic, or muscarinic systems, according to its developer, Acadia Pharmaceuticals.
Although Acadia submitted just one positive phase III trial out of a total of four 6-week, randomized, placebo-controlled trials of pimavanserin, committee members voted 12-2 that the company “provided substantial evidence of the effectiveness” of the drug for the treatment of psychosis associated with Parkinsons’s disease (PDP). Another 11-3 vote supported the question of whether pimavanersin’s safety profile was “adequately characterized.”
Results from the single phase III trial conducted in 199 patients with Parkinsons’s disease psychosis (PDP) unequivocally showed that 34 mg/day pimavanserin improved scores on an abbreviated, 9-item version of the 20-item Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions score, called the SAPS-PD. After 6 weeks, SAPS-PD scores declined by a statistically significant 3.1 points or 23.1% on active treatment versus placebo, which was an absolute decrease of about 6 points from baseline. One of the questions brought up by FDA reviewers and panelists was whether the 3.1-point difference (on the SAPS-PD’s 45-point scale) seen between active treatment and placebo was of great enough clinical benefit to outweigh the higher rate of serious adverse events observed with pimavanserin versus placebo across all of the 6-week trials.
Across all four 6-week studies, serious adverse events occurred in 16 (7.9%) of 202 patients who took 34 mg pimavanserin and in 8 (3.5%) of 231 placebo-treated patients. Three deaths occurred in the patients who received pimavanserin, and one in the placebo arms. However, none of the deaths were considered to be a drug-related event, and the deaths were not pathologically unique relative to what is expected in the disease course of patients with PDP. The death of another patient who had received 10 mg pimavanserin in an earlier uncontrolled trial also was reported.
Meanwhile, the drug did not worsen motor symptoms of Parkinson’s disease.
FDA analyses showed that 11 patients would need to be treated in order for 1 patient to have a 50% reduction in the SAPS-PD, which corresponds to “much improvement,” whereas 22 patients would need to be treated for 1 to be harmed with a serious adverse event (SAE). This means that for every two patients who have a 50% reduction in the SAPS-PD, one will have a serious adverse event attributable to pimavanserin. Overall, 37.2% of patients in the pimavanserin arm of the phase III trial had a 50% decline in the SAPS-PD after 6 weeks, compared with 27.8% in the placebo arm.
However, the number needed to harm/number needed to treat ratio for SAEs had wide confidence intervals, and there was a high degree of uncertainty about its magnitude such that the inclusion of just one or two more SAEs would substantially change the ratio, many panelists agreed.
Some panelists voiced concern about pimavanserin being called an antipsychotic, even though it has demonstrated no proof of efficacy in conditions with classical symptoms of psychosis, such as schizophrenia, and worried about its off-label use in patients with other conditions who have psychotic symptoms. They also called for a postmarketing observational study to track the safety of the drug if it is approved.
Pimavanserin’s application received breakthrough drug status from the FDA and was fast tracked, and a decision is expected from the agency by May 1. If approved, pimavanserin would be marketed under the trade name Nuplazid.
