J&J Finalizing Risperdal Consta Resubmission; Approval Possible By Year-End

Johnson & Johnson is finalizing its response to a Risperdal Consta "not approvable" letter received from FDA last year.

"We should be filing a complete response in the pretty near future," J&J VP-Investor Relations Helen Short said during an analysts call April 15.

J&J received the "not approvable" letter for Risperdal Consta - an Alkermes-developed sustained-release formulation of J&J's antipsychotic - risperidone June 28 (¹ 'The Pink Sheet' July 8, 2002, In Brief).

"Since that time, [J&J] has been working internally and with the agency to develop a comprehensive response to the pre-clinical toxicology issues that have been raised," Alkermes CFO James Frates said during a SG Cowen analyst meeting March 19.

The two companies anticipate a six-month PDUFA clock on their response. "We're building our business model for this year...for approval of Risperdal Consta in the U.S. by the end of this calendar year or soon thereafter," Frates said.

FDA approved an orally disintegrating tablet form of Risperdal April 2. J&J submitted an sNDA to support use of Risperdal as both adjunctive and monotherapy in the treatment of manic symptoms associated with bipolar disorder in December.

J&J could use the different administration forms of Risperdal to distinguish between indications for the antipsychotic.

The long-acting injectable Risperdal Consta appears to be ideally suited for use in the schizophrenia market, while the currently marketed tablet form of risperidone could be more targeted to treat bipolar disorder.

"The opportunity...for a depot injection for these drugs is important because the cost of non-compliance, when schizophrenics do not take their medication...can be quite devastating," Frates explained.

"And the cost of non-compliance, again, with the relapse rate, hospitalization and other costs to the family are quite high. So this is going to be a nice opportunity for Risperdal Consta to potentially fill this need," Frates stated.

J&J began an advertising campaign in the fall stressing the importance of compliance.

An ad currently running in the American Journal of Psychiatry shows an iceberg with only its tip above the water. The ad states, "For anyone who thinks that partial compliance of schizophrenia is a small problem, three out of four patients with schizophrenia are only partially compliant with their antipsychotic medication."

The Risperdal Consta resubmission will presumably reflect updated labeling for Risperdal warning of a potential risk of stroke. Updated labeling warns of cerebrovascular adverse events reported "in trials of risperidone in elderly patients with dementia-related psychosis."

J&J will send a "Dear Health Care Professional" letter in the U.S. regarding the additional warning in the near future (² 'The Pink Sheet' April 14, In Brief).

The company sent a letter on the topic to Canadian physicians in October.

"While elderly patients are at an increased risk of [cerebrovascular adverse events]," the letter says, "the above clinical trial data reflect an increased incidence of such adverse events in patients taking Risperdal compared with age-matched, placebo-treated dementia patients."

J&J's well-established presence in the nursing home market may make the new warning a more significant issue for Risperdal. Risperdal, in fact, is often used off-label as a treatment of dementia in elderly patients.

The new stroke warning for Risperdal is part of a round of publicity surrounding potential side effects associated with the antipsychotic class.

The most prominent issue continues to be metabolic effects associated with Lilly's Zyprexa ; FDA is weighing whether there is a product or class effect that merits a labeling change. Zyprexa and AstraZeneca's Seroquel (quetiapine) received diabetes label changes in Japan (³ (Also see "Lilly Expects Zyprexa Sales To Flatten During Bristol Abilify Launch In Q4" - Pink Sheet, 28 Oct, 2002.), p. 24).

The Department of Veterans Affairs is expecting data on diabetes associated with Zyprexa in June (see ⁴ (Also see "Schizophrenia Drugs And Diabetes: VA Data On Causal Link Expected In June" - Pink Sheet, 21 Apr, 2003.) ).