Amid safety concerns, FDA adcomm set to review Acadia's Parkinson's drug
- Acadia Pharmaceutical’s Parkinson’s antipsychotic drug will face regulatory scrutiny in a FDA advisory committee review set for tomorrow. Known as Nuplazid, the drug has been in clinical development for roughly a decade for the treatment of psychosis in Parkinson's disease (PDP).
- While recognizing the drug’s efficacy, an earlier FDA assessment raised concerns over increased morbidity and mortality risks. There is currently no approved drug for the treatment of PDP.
- In the phase 3 pivotal clinical trial which forms the backbone of Acadia’s submission, Nuplazid 34 mg showed efficacy in treatment of PDP symptoms. However, subjects treated with the drug had over twice as high rates of severe adverse events, compared to the placebo group.
In a phase 3 clinical trial involving 433 patients, Nuplazid showed efficacy in PDP based on changes in the nine-item SAPS-PD scale, which has been modified from a scale originally developed for schizophrenia.
While this level of efficacy was seen as highly positive—especially considering the dearth of treatment options specifically for PDP patients—the high level of serious adverse events, in addition to evidence of an increased risk of death during treatment, raises doubts about the drug’s trade-offs. In the six-week trial, 7.9% of subjects treated with Nuplazid experienced severe adverse events, compared with 3.5% of placebo-treated subjects.
Numerous studies dating back to the 1990's have shown that treatment of PDP increases the risk of death in patients with PD. A recent study from the University of Pennsylvania looked at data from the Veteran's Affairs database on 15,000 patients to assess the risk between treating PDP and mortality. Their analysis revealed a two-fold risk of death associated with treatment.
As there is no approved treatment for PDP, treating practitioners have traditionally prescribed antipsychotics such as Haldol (haloperidol), and, more recently, atypicals. A closer look at the data reveals large differences in the risk of death associated with these two classes of antipsychotics. For example, Haldol increases the risk of death five-fold in PDP patients, while a newer treatment, olanzapine, increases risk by a factor of 2.79. One of the challenges with assessing the data clearly is that so far no mechanism has been found that might explain the increased risk of mortality.
Assuming eventual FDA approval, Nuplazid has been forecast to hit $1.41 billion in 2020 sales, according to Thomson Reuters Cortellis.
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