Alkermes Inc. said partner Johnson & Johnson submitted everything the FDA should need to consider Risperdal Consta for approval, effectively resetting the PDUFA clock for an agency response in the fourth quarter.

"That's why we called it a complete response,'" said Richard Pops, Alkermes' CEO, adding that the company handed in "specific analyses and data," and it addressed "the non-approval issues that were raised last summer."

On top of that, the company responded to "a series of questions that you would find in an approvable letter," which were included in the FDA's non-approvable letter back in June. That done, Cambridge, Mass.-based Alkermes can sit back and wait to see if the U.S. will be added to the list of countries in which Risperdal Consta is approved.

"[The FDA has] six months to respond," Pops said.

Risperdal Consta is a long-acting injectable form of risperidone and is designed to be given once every two weeks to manage schizophrenia. The drug uses Alkermes' delivery technology, Medisorb, which encapsulates risperidone in microspheres made of a biodegradable polymer. The product was developed by Alkermes and Johnson & Johnson Pharmaceutical Research & Development, with the J&J unit having global sales and marketing responsibilities and Alkermes taking care of worldwide manufacturing.

The companies submitted their new drug application in August 2001 and received the non-approvable letter the following June. What, specifically, the FDA had concerns with was not publicly released by Alkermes, but industry observers pointed to preclinical data and increased cancer risks in rodents. Alkermes' stock took a major hit on the news last year, dropping $10.86, or 67.8 percent, to close at $5.15.

Alkermes' stock (NASDAQ:ALKS) fell $1.09 Tuesday, or 10.4 percent, to close at $9.41, a loss that might be attributed to a downgrade from "strong buy" by investment firm SG Cowen Securities Corp. Cowen said before the market opened Tuesday that Alkermes now was fairly valued and had gained in anticipation of the filing.

The non-approvable letter eventually helped cause the "mutual termination" of a planned Alkermes equity merger with Reliant Pharmaceuticals LLC, of Liberty Corner, N.J. Dropping stock prices devalued that deal by nearly $675 million from its original assumed price of $934 million when it was first announced in March 2002. For Alkermes, that busted merger was followed by a 23 percent staff reduction in August as the company reduced spending due to the delay of expected Risperdal Consta revenue in the U.S. (See BioWorld Today, March 22, 2002; Aug. 15, 2002; and Aug. 27, 2002.)

It will be J&J that launches the drug, so while Alkermes is producing commercial product for the countries in which Risperdal Consta has been launched, Pops said, "The milestone we are focused on now is U.S. approval."

Alkermes receives worldwide royalties on Risperdal Consta sales and gets manufacturing fees. The product is on file in 42 countries, approved in 23 and launched in seven, so regardless of how it fares in the U.S. this time around, the company should see an increasing Risperdal Consta revenue stream. Pops said the word from J&J is that Risperdal Consta's "early performance has exceeded their expectations."

As of Dec. 31, the company had cash and investments of $167.1 million. It posted a pro forma net loss of $12.8 million for the quarter. Its 2002 fourth quarter ended March 31 and the company is due to release its year-end figures the third week of May.

Alkermes has Nutropin Depot for pediatric growth hormone deficiency approved, partnered with Genentech Inc., of South San Francisco, and featuring Alkermes' ProLease technology. The product is in Phase III trials in adults. The Medisorb technology also is on display in Vivitrex, an injectable form of naltrexone. That product is in Phase III trials in alcoholism and opiate abuse. The company also is working with Eli Lilly and Co., of Indianapolis, and Amylin Pharmaceuticals Inc., of San Diego, in diabetes. The approval of Risperdal Consta would mean a couple of things, Pops told BioWorld Today.

"Risperdal Consta is a very important product for us for two reasons," he said. "No. 1, its important [in the treatment of schizophrenia], and No. 2, it's our first product that is based on the Medisorb technology. Risperdal Consta is important as an independent product and it also is indicative of the general capabilities of the company."