US FDA wants more data on once-monthly Invega
This article was originally published in Scrip
The US FDAhas asked Johnson & Johnsonin a complete response letter to provide additional information on paliperidone palmitate, its investigational once-monthly formulation of Invega (paliperidone), for treating schizophrenia and preventing recurrence of symptoms.
The agency does not require any additional studies, but the letter outlines the remaining questions that need to be addressed before paliperidone palmitate can be approved, J&J said. The company told Scrip that it was still reviewing the letter and should have more details on its response and how it might delay approval ahead of the next investor briefing in October. This is the second complete response request J&J has received in a week, following the FDA's letter about Doribax (doripenem), an intravenous antibiotic (Scrip Online, August 26th, 2008).
The NDA for paliperidone palmitate was submitted in October last year. The filing included data from 3,000 patients included in Phase III studies which examined the primary endpoints of PANSS-total (in acute patients) and time to relapse (in patients who had been previously stabilised) and met both these endpoints.
Paliperidone palmitate uses Elan's NanoCrystal technology to create a once-monthly intramuscular formulation of the atypical antipsychotic (paliperidone, a full serotonin and partial dopamine D2 antagonist. Paliperidone is itself an oral controlled-release (once-daily) formulation of the principal active metabolite of Johnson & Johnson's older antipsychotic Risperdal (risperidone), available in an oral formulation as well as a longer-acting intramuscular formulation, Risperdal Consta, which is dosed once every two weeks.
Paliperidone palmitate has the advantage over Risperdal Consta of not needing to be refrigerated or reconstituted, making it easier to dose, and it uses a smaller needle (as well as being dosed intramuscularly once a month, rather than every two weeks). The efficacy and side-effect profile of Risperdal Consta and paliperidone palmitate are being compared in a Phase III trial expected to be completed next year. However, Johnson and Johnson said it believed that each of the formulations will have advantages for particular patients and that the availability of paliperidone palmitate will provide further treatment options for patients.
The US patent exclusivity of Risperdal's oral formulation expired earlier this year and, in July, Teva Pharmaceutical Industries launched a generic oral version of risperidone. In addition, Invega has so far performed below expectations in the US, partly because of formulary restrictions, and has been declined by national reimbursement schemes in Denmark, Scotland and Sweden. However, analysts at Credit Suisse are optimistic about the potential of paliperidone palmitate and have predicted blockbuster sales of the product.
Other atypical antipsychotics for schizophrenia, such as Otsuka and Bristol-Myers Squibb's Abilify (aripiprazole), Pfizer's Geodon (ziprasidone) and Lilly's Zyprexa (olanzapine), are available as once-daily tablets for acute and maintenance treatment and as intramuscular injections for acute episodes. AstraZeneca's Seroquel XR (quetiapine fumarate) is only available as a once-daily tablet.