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FDA Rejects Arpida's Iclaprim as Company Seeks a Partner

BioWorld Today Correspondent

Although the news was hardly a surprise, shares in Arpida AG still dropped by more than 4 percent Tuesday, following confirmation from the FDA that it would require additional clinical data to approve the Swiss firm's antibiotic iclaprim.

A straight approval of the drug, which is in development for treating complicated skin and skin structure infections (cSSSIs), was never in the cards, following a 17-to-2 vote against from the FDA's Anti-infective Drugs Advisory Committee in November.

The FDA's complete response letter, which the company disclosed on Monday, called for an additional clinical study - or studies - to demonstrate the drug's efficacy.

"It's been stated in broad terms what they think should be done to achieve approval," Harry Welten, chief financial officer of Reinach, Switzerland-based Arpida, told BioWorld Today. It would cost between CHF20 million (US17.5 million) and CHF40 million to fund the necessary trials.

"It goes without saying that this is not within our reach," he said. The company therefore is seeking a partner to take on further development of the drug, a diaminopyrimidine dihydrofolate reductase inhibitor, while also engaging with the FDA to determine what precisely is required.

It also is proceeding with a major cost-cutting program, which was announced late last year. The company is laying off three-quarters of its staff and paring its payroll back to 20 people, to conserve cash and buy more time.

This week, the company disclosed that its board also is being reduced. Former CEO Khalid Islam has resigned as a director, although he remains available to the company as a consultant, and Axel Kleemann will not seek re-election at the company's next shareholder meeting.

Arpida also is halting all its early development programs. "Iclaprim is the key asset, which we are focusing our attention on now," Welten said.

The company has yet to hear from the London-based European Medicines Agency (EMEA), which accepted a dossier for review last August, although it is not making any encouraging noises here either.

"We're going to know more in Q3," Welten said.

The stock (ZURICH:ARPN), which is down 94 percent year-on-year, closed at CHF0.86 Tuesday, down CHF0.04 from the previous day. The company has forecast a cash balance of approximately CHF38 million by the end of 2008 and around CHF17 million by the end of this year.

Arpida's shares took a 54 percent hit in November after an FDA analysis of Phase III data of iclaprim raised significant concerns about its efficacy and safety, with three deaths suspected of being related to the drug. (See BioWorld Today, Nov. 19, 2008.)

The analysis showed that iclaprim was less effective than New York-based Pfizer Inc.'s Zyvox (linezolid), which conflicted with the results released by Arpida in July 2007 and December 2006.

The FDA analysis showed that Arpida's Phase III studies comparing iclaprim with Zyvox, known as ASSIST-1 and ASSIST-2, failed to meet noninferiority to the prespecified margin of 12.5 percent.

The lower bound of the 95 percent confidence interval for the treatment difference of the clinical cure at the test-of-cure period between iclaprim and Zyvox exceeded the FDA's determination of the noninferiority margin of 10 percent in most of the intent-to-treat and per-protocol co-primary analyses, the agency's drug reviewers stated.

In addition, the upper limit of the 95 percent confidence interval for the treatment difference failed to cross zero in ASSIST-1, the reviewers said.

The FDA's analysis showed there were six deaths among patients treated with iclaprim in the two Phase III studies, with three of those deaths assessed by the agency as "possibly related" to the medication.

Renal adverse events comprised 2.8 percent of all adverse events reported in the iclaprim group, regulators said, adding that there were no drug discontinuations due to treatment emergent renal failure or azotemia, a buildup of nitrogen-type wastes, such as creatinine and urea.

Published: January 21, 2009