Fidaxomicin – Narrow-Spectrum Antibiotic for Clostridium Difficile Infection

Fidaxomicin is a new class of antibiotics developed by Optimer Pharmaceuticals to treat Clostridium difficile infection (CDI). The drug, formerly known as OPT-80, PAR-101 or Difimicin, is undergoing a second Phase III clinical trial.

The first Phase III clinical trial of the drug reported results in November 2008. Conducted in North America, the trial demonstrated positive results for its primary and secondary endpoints.

Results of the second Phase III trial, if positive, will allow the company to file a new drug application with the US registration. The results of the second Phase III trial are due by early 2010.

Targeting CDI

CDI is a growing illness that spreads largely in hospitals, long-term healthcare facilities and in community settings. Caused by Clostridium difficile (C. difficile), gram-positive bacteria that creates severe infection in the colon, CDI results in severe diarrhoea, colon inflammation and in extreme cases even death.

In 2007, the disease was believed to have led to over 8,000 deaths in the UK. Broad-spectrum antibiotics that destroy the normal gut flora of humans are the prime reason for the growth of C. difficile.

Elderly people with weak immune systems, or people who have had an extended stay in a healthcare environment, are vulnerable to the disease. Treatment options for CDI include oral Vancocin, the only US Food and Drug Administration (FDA)-approved therapeutic option and off-label use of metronidazole. Approximately 20–30% of patients who had responded to these treatments witnessed a recurrence of the disease once the medication was stopped.

Fidaxomicin inhibits RNA polymerase

Rather than merely halting bacteria growth, Fidaxomicin leads to the death of C. difficile by inhibiting RNA polymerase, a bacterial enzyme that kills specific bacteria. Unlike broad-spectrum antibiotics, Fidaxomicin is a narrow-spectrum antibiotic that maintains the natural balance of flora while destroying C. difficile in the gastrointestinal tract.

It has minimal systematic exposure, low resistance from C. difficile and a convenient dosing regimen. By returning the colon's physiological conditions to normal, Fidaxomicin-based treatment also results in a lower recurrence rate.

Clinical trials

The superiority of Fidaxomicin was proved over Vancocin in the first Phase III clinical trial that was performed on over 629 adults. Conducted at over 100 clinical sites across North America, the trial demonstrated that a ten-day course of Fidaxomicin is as safe and at least as effective as a same-period course of Vancocin for treating CDI. Patients were dosed with either 200mg of Fidaxomicin twice daily or 125mg of Vancocin four times in a day in the multi-centre, randomised, double-blind clinical trial.

Results proved that Fidaxomicin not only has a higher cure rate globally but also resulted in lower recurrence among patients. Patients required no CDI medication two days after the treatment was completed and showed no recurrence even after four weeks of ending the therapy.

The second Phase III clinical trial, which enrolled 536 adults, will further evaluate the safety and efficacy of Fidaxomicin in comparison to Vancocin. The multi-centre, randomised, double-blind trial is being conducted at approximately 100 sites throughout North America and Europe.

It will measure and compare patients' response to treatment during and after a ten-day therapy course, as well as evaluating the recurrence and global cure rate with Fidaxomicin.

As in the first Phase III clinical trial, patients in the second Phase III clinical trial will be given 200mg of Fidaxomicin twice daily or 125mg of Vancocin four times in a day.

Oral suspension formulation

Apart from the tablet form, Fidaxomicin will be developed as an oral suspension formulation by Optimer Pharmaceuticals. The formulation will be used within intensive care units and for elderly patients. Optimer Pharmaceuticals is also planning to file for an Investigational New Drug application to develop Fidaxomicin for additional indications.