Tigecycline would add to resistant infection armory

The FDA's decision to grant Wyeth's tigecycline priority review status is a welcome one. Wyeth recently presented data on tigecycline, the first drug in a novel class of antibiotics, which showed that the drug demonstrated efficacy against a wide variety of bacterial infections, including MRSA. Tigecycline's entry onto the market would be timely, as global concern mounts over such 'superbugs'.

Despite fears that the world may be running out of effective antibiotics, data presented at the recent European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) on various compounds highlighted that potential advances in the battle against drug resistance bacterial infections are not too far away. One such drug offering hope against resistant infections is Wyeth's candidate tigecycline, provisionally known as Tygacil, which was submitted for approval in December 2004.

Tigecycline is the first in a new class of antibacterials known as glycylcyclines, and is derived from the minocycline molecule. It has demonstrated activity against tetracycline-resistant gram-positive and gram-negative pathogens, with an identical mode of action to tetracycline except for the position nine substitution of tigecycline, which provides additional steric hindrance features and resulting greater spectrum of activity.

Wyeth filed the submission for global regulatory approval for tigecycline at the end of last year with the FDA, EMEA and authorities in Canada and Australia. Approval is sought for tigecycline as a monotherapy to treat patients with complicated intra-abdominal infections and complicated skin and skin structural infections caused by gram-negative and gram-positive pathogens, anaerobes and both methicillin resistant strains of Staphylococcus aureus (MSSA and MRSA).

Promising data

Data presented at the ECCMID included a study on infections obtained in intensive care units, where tigecycline was highly active against the most frequently isolated pathogens, including resistant strains, although not the difficult to treat Pseudomonas aeruginosa. Most significant was the data presented on the drug's activity against common resistant pathogens, including the increasingly prevalent MRSA.

The problem of resistant bacterial infections, in particular MRSA, has been gathering pace, with incidence increasing throughout the seven major markets. Recent data from the US highlighted to the growing issue of community acquired MRSA, and outbreaks of infection in UK hospitals are common. According to a recent National Audit report from the UK, MRSA rates are rising dramatically across Europe, with the UK, Ireland, Greece and Italy having the highest rates. Within these, the proportion of MRSA rates is highest among patients admitted to intensive care units. In the light of this, UK politicians and health officials are due to attend a conference in London, known as the Clean Hospitals Summit, to discuss the best way to deal with hospital acquired infections.

Although there are several antibacterials available for the treatment of resistant infections, such as Pfizer's Zyvox (linezolid), King Pharmaceutical's Synercid (dalfopristin / quinupristin) and Cubist's recently approved Cubicin (daptomycin), there is still a need for new drugs. Tolerability issues, for example, prevent the prolonged use of Zyvox, which runs the risk of the development of myelosuppression. Furthermore, Synercid is only available in injectable formulation, preventing its use outside of the hospital. Moreover, these drugs are not active against all strains of resistant bacteria.

Regulatory backing

The urgent need for new antibiotic treatments has led to the FDA designating tigecycline priority review status, which is granted to drugs that offer the potential for radically improved options in extremely difficult-to-treat therapeutic areas. Data presented at ECCMID showed that tigecycline monotherapy exhibited antibacterial activity against a wide range of bacteria commonly found in patients hospitalized in intensive care units worldwide.

The issue of bacterial resistance is not a new one, but is adopting a greater significance as cases of infection increase. Indeed, reports from the UK National Audit Office state that at any one time, 9% of NHS hospital patients are suffering from an infection acquired while in surgery or as an outpatient on the hospital wards.

These infections affect 100,000 people, cause up to 5,000 deaths and are estimated to cost the National Health Service up to GBP1 billion per year. Faced with the increasingly pressing problem of growing resistance to many of the currently available broad-spectrum antibiotics, especially in the fight against MRSA, the approval of tigecycline would provide another valuable addition to the armaments against resistant infections.

Related research: 

• Commercial Insight: Antibacterials - Regulations, Resistance & Generics priced $15,200
• Stakeholder Opinions: Skin Infections - Where In The Antibacterial Lifecycle? priced $3,800
• Stakeholder Opinions: Urinary Tract Infections - Ciprofloxacin Leads the Way priced $3,800

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