Agency also pointed to a number of safety issues.

The FDA has found that it cannot approve Targanta Therapeutics’ oritavancin since the NDA did not demonstrate safety and efficacy for treatment of complicated skin and skin structure infections (cSSSI) under the current NDA. The agency requires an additional well-controlled clinical study to demonstrate efficacy and safety.

On November 19, the agency’s advisory committee voted against the approval of oritavancin for the treatment of cSSSI. The firm’s shares dropped from $7.75 at the close of November 19 to $1.38 the next day’s closing. The company has been struggling ever since and opened today at $0.85.

In a conference call, Mark Leuchtenberger, president and CEO, expressed surprise over FDA’s requirements. He said that while the firm expected a complete response letter as opposed to  a complete approval, the extent of the agency’s requirements were unexpected.

Leuchtenberger went on to say that the company would meet with the FDA to evaluate the best way to proceed and stressed that the company was commited to bringing this drug to market.

Howard Liang, biotechnology equity research analyst for Leerink Swann, downgraded Targanta from an outperform to market-perform status based on the FDA’s decision and uncertainties in the MRSA market.

The FDA specifically asked that a sufficient number of patients with MRSA as the cause of cSSSI be enrolled in the study to demonstrate the effectiveness of the drug in this subset of patients. The agency also suggested that the clinical study evaluate the effect of oritavancin on macrophage function and monitor for subsequent infections that could possibly be related to macrophage dysfunction due to the long terminal half-life of oritavancin. Additionally, the clinical study would need to collect additional information on phlebitis rates.

The FDA in its complete response letter to Targanta stated that ARRI, the second and larger of two Phase III studies, which met a 10% noninferiority margin, provided evidence of activity of oritavancin. It did not provide, however, substantial evidence alone or in combination with ARRD, the smaller of two Phase III trials, to support the efficacy and safety of oritavancin. The agency notes that ARRD did not provide sufficient evidence of activity. Additionally in ARRI oritavancin did not appear to perform well in patients with MRSA, and in ARRD the number of patients with MRSA was insufficient.

The FDA also pointed to several safety findings from the two pivotal studies, including the higher rate of study discontinuations for lack of efficacy among oritavancin-treated patients, the greater number of oritavancin-treated patients who died, or had a serious adverse event of sepsis, septic shock, and related events, and more oritavancin-treated patients who experienced adverse events of osteomyelitis and other sepsis.

Targanta is developing oritavancin in other indications including catheter-related bacteremia. Oritavancin is a semisynthetic lipoglycopeptide antibiotic candidate with potent bactericidal activity against a broad spectrum of gram-positive bacteria.

The oritavancin NDA submission included data from 19 trials. The NDA dossier also included data from more than 2,100 individuals and in vitro activity data on oritavancin against more than 9,000 clinical bacterial isolates including a broad range of gram-positive strains resistant to commonly used antibiotics such as oxacillin, methicillin, vancomycin, daptomycin, and linezolid.

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