Cidecin Manufacturing Issues Could Delay Launch By “A Number Of Weeks”

Manufacturing issues are likely to delay the launch of Cubist's cyclic lipopeptide antibiotic Cidecin by "a number of weeks" after the anticipated Sept. 20 approval, the firm said.

"The issue has been that the yields have not improved at the rate we had expected them to, and that is requiring us to run a couple more batches to get to [a] finished goods inventory level that we're comfortable with," CEO Michael Bonney said during a June 18 conference call.

Bonney reassured analysts that the manufacturing issues will be resolved and are not a recurring problem. "It's really just a one-time issue having to do with getting through the inspection and getting more clarity on final specs and so forth," he said.

"We're talking about a potential delay, assuming a Sept. 20 approval, measured in a number of weeks-not extended beyond that."

The manufacturing delay is on top of a three-month extension of Cidecin's user fee goal date, from June 20 to Sept. 20. The agent is receiving a priority review for complicated skin and skin structure infections caused by Gram-positive organisms, including antibiotic-resistant strains of Staphylococcus aureus (¹ Pharmaceutical Approvals Monthly March 1, 2003, p. 6).

FDA's June 17 extension is the result of the submission of reformatted data sets for the two pivotal studies in the Cidecin NDA, the firm said, adding that no new data or analyses were submitted.

"Basically, late in the review process, it became apparent to us that the FDA was having difficulty navigating certain sections of the electronic submissions due to some electronic formatting issues," Bonney said.

"At this point, we have not had any questions from the agency that would suggest that there are concerns about the fundamental issues of safety and efficacy."

"What ultimately led us to understand that the issue was navigability of the database were questions on specific individual patients, one or two of them, in terms of how they met the evaluability criteria in the core studies."

One analyst commented that the last time FDA had a reformatting issue with an e-submission was about four years ago "on a product that still hasn't received approval." GlaxoSmithKline/Corixa received a refuse-to-file letter in August 1999 for Bexxar , including a reformatting request. The lymphoma treatment was approved June 27, eight days after the Cubist call.

Bonney maintained that "over the last couple of weeks…we've actually had people at the agency working side by side with them to help navigate through the data sets, and there don't appear to be…a ny issues that would suggest" the need for additional data.

The firm re-emphasized its U.S. launch plans, stating that "we are going to attack the U.S. market as Cubist" with "a Cubist only...sales and marketing organization."

While Bonney declined to provide revenue estimates for Cidecin, he pointed out that in 2002 there were 30 mil. patient days of I.V. antibiotics administered for Gram-positive infections in U.S. hospitals, 17 mil. of which came solely from vancomycin treatment.

"If you make a price assumption," with Cidecin "somewhere between [Roche's] Rocephin [ceftriaxone], which is $40 to $60 a day, and linezolid [Pfizer's Zyvox ], which is $130 a day, and then make what you believe to be the penetration assumption that this drug will achieve, you can arrive at a revenue number."

In the EU, Cubist expects to conclude talks with potential marketing partners by year-end. Cubist has been meeting with authorities "to get clarity" on whether the centralized or mutual recognition procedure is best for a European filing.

Bonney noted that the EMEA recently issued a draft guidance on antibiotics indicating that when resistance is a problem, demonstrating non-inferiority for a single indication, as in the Cidecin NDA, is acceptable for filing.

"There seems to be some growing momentum in Europe, as there is in the U.S., that resistance, particularly in Gram-positive organisms, is a serious problem, and the lack of new drugs to treat this needs to be addressed from a regulatory standpoint."