Companies take various approaches to revealing the information that is contained in a Complete Response Letter from the FDA, but Targanta Therapeutics Corporation (NASDAQ: TARG) was very thorough in its press release this week. It is not uncommon for small pharma companies to not win approval in their early efforts – in fact it is quite common. But Targanta's handling of the matter signals a company that is unusually willing to be highly transparent and open, and that must be a comfort to investors.
The product is called oritavancin and it is for the treatment of complicated skin and skin structure infections (cSSSI). The company not only issued a very thorough press release detailing the issues that the FDA had with the application, but held a Webcast as well
. While the news could not have been a surprise after the Advisory Committee outcome
, the detail that the company went into with investors went very far. From the press release:
The FDA indicated in its letter that they cannot approve the application for oritavancin in its current form and will require Targanta to perform an additional well-controlled clinical study to demonstrate efficacy and safety in order to gain approval. The FDA requested that a sufficient number of patients with methicillin-resistant Staphylococcus aureus (MRSA) as the cause of cSSSI be enrolled in the study to demonstrate the effectiveness of oritavancin in this subset of patients. The FDA further suggested that the clinical study evaluate the effect of oritavancin on macrophage function and monitor for the potential for subsequent infections that could possibly be related to macrophage dysfunction due to the long terminal half-life of oritavancin. The FDA also requested that the clinical study collect additional information on phlebitis rates.
In its letter to Targanta, the FDA stated the Company’s NDA did not demonstrate the safety and efficacy of oritavancin for treatment of cSSSI. The FDA reasoned that ARRI, the second and larger of two Phase 3 clinical studies which met a 10% non-inferiority margin, provided evidence of activity of oritavancin but did not provide substantial evidence alone or in combination with ARRD, the smaller of two Phase 3 clinical studies, to support the efficacy and safety of oritavancin. Regarding ARRD, the FDA determined that the study did not provide sufficient evidence of activity because the 95% confidence interval between oritavancin and vancomycin was not less than 10%. FDA also mentioned that, in ARRI, oritavancin did not appear to perform well in patients with MRSA and, in ARRD, the number of patients with MRSA was insufficient to address the performance of the drug candidate in treating these patients.
The FDA mentioned several safety findings from the two pivotal studies for cSSSI 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.
The Targanta approach bears noting and certainly adds to the spectrum of company reactions to FDA Complete Response Letters. Meanwhile, here is an update of the chart on approvals versus CRLs.