Wyeth seeks approval of new class antibiotic

Wyeth​ is seeking market approval for Tygacil as a single agent therapy to treat patients with complicated intra-abdominal infections (cIAI) and complicated skin and skin structure infections (cSSSI).

Tygacil is causing waves within the industry as it becomes the first effective therapy to treat infections caused by gram-negative and gram-positive pathogens, anaerobes, and both methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus (MSSA and MRSA).

Virtually all main classes of bacteria have developed resistance to one or more classes of antibiotics. Future antibiotics will need to be active broadly, not just against the usual "suspects," frequently seen disease-causing bacteria, but also against new strains, particularly those with resistance.

In particular, hospitals face an increasing clinical challenge as current efforts to prevent and control antimicrobial resistance in the hospital and community are inadequate. In fact, more and more patients admitted to hospitals from the community are presenting with antibiotic resistant bacteria that were previously only found within the hospital environment. This issue is compounded by the fact that few broad-spectrum antibiotic agents are currently in development to fight existing and emerging resistant bacteria.

Tygacil is described by Wyeth as a structurally distinct and re-engineered tetracycline. A modification at the ninth position of its core structure enables it to bind to the 30S ribosomal subunit with increased affinity compared with any prior generation tetracycline. This means it can overcome typical bacterial resistance to tetracyclines mediated by efflux pumps and ribosomal protection.

"Tygacil is the first glycylcycline, a new class of antibiotic, with the potential to be a monotherapy option for clinicians treating complicated skin and skin structure infections and complicated intra-abdominal infections,"​ says Dr. Robert Ruffolo, president of Wyeth research.

"Complicated infections and antibiotic resistance are serious concerns around the world, and the hope is that Tygacil will provide the global medical community with a much needed treatment alternative."​

The submission included data from four phase III studies examining the safety and efficacy of Tygacil. The filing also included in vitro data against both gram-negative and gram-positive bacteria, and anaerobes, including drug-resistant pathogens. The most common adverse events associated with Tygacil in clinical trials were nausea and vomiting.

This is the first time Wyeth has applied simultaneously for global approval of a new product. The registration package included the submission of a New Drug Application (NDA) with the US Food and Drug Administration (FDA). Marketing Authorization Application (MAA) with the European Medicines Agency and additional filings were also applied for with authorities in Canada, Australia, and Switzerland.

According to the US Centres for Disease Control and Prevention (CDC), antibiotic resistance has become so widespread that many significant bacterial infections in the world are becoming resistant to commonly used antibiotics.

Bacteria that have become resistant to previously effective antimicrobials include pneumococci, staphylococci, enterococci, E. coli, Enterobacter,​ and Acinetobacter.​

A paper published in the medical journal Clinical Infectious Diseases​ in April 2004 found just five of thirty-one anti-infectives currently in development at the world's fifteen largest pharmaceutical companies were antibacterial agents.

Dr. Sherwood Gorbach, professor of public health and medicine, Tufts University School of Medicine said: "Increasing antibiotic resistance in hospitals can lead to treatment failure, poor patient outcomes, and increased cost."​

"In times where the antibiotic pipeline is declining, the filing of new antibiotics could not be more appropriate."​