Generic Threat to Optimer Pharma's Fidaxomicin Antibiotic

The relative efficacy of Optimer Pharma’s investigational antibiotic, fidaxomicin, compared to standard-of-care vancomycin (marketed as Vancocin by drugmaker ViroPharma), remains unclear. Published results show similar recurrence rates in a subset of patients infected with a life-threatening strain of the hospital-acquired gastrointestinal infection Clostridium difficile. In my opinion, even if Optimer obtains regulatory approval to market fidaxomicin, its commercial success will be limited, as the FDA is likely to move forward on an advisory committee’s recommendation for the sale of cheaper generic copies of Vancocin.

Optimer reported top line data from a late-stage study in November 2008, showing that fidaxomicin met both its primary endpoint of clinical cure (defined as patients requiring no further therapy two days after completion of study medication) and secondary endpoint (which evaluated recurrence up to four weeks post therapy, with recurrence defined as the return of diarrhea associated with C. difficile confirmed by a positive toxin test).

A more detailed analysis of the Phase 3 study presented at the 19th annual European Congress of Clinical Microbiology and Infectious Diseases in May, however, showed that fidaxomicin was no more effective compared to Vancocin in a subset of patients with the most virulent strain (known as BI/NAP1/ribotype 027). The recurrence rates for fidaxomicin and Vancocin in the BI/NAP1/027 subgroup were 25 percent and 24.1 percent.

Relapse with the same or different strains occurs in about 10 percent to 35 percent of patients treated with either oral vancomycin or the oral anti-infective metronidazole (off-label usage). Although fidaxomicin affords no special protection from recurrence with the hyper-virulent strain, chief financial officer John Prunty remains optimistic, telling Xconomy editor Luke Timmerman that looking at the results and simply inferring the market just shrunk by one-third would be a mistake:

“Doctors faced with a diagnosis of “C.Diff” are dealing with an emergency that requires immediate treatment. The current lab tests that are sensitive enough to tell the difference between normal C.Diff and the hypervirulent form take three weeks to produce a result. [Ed. Note. The most common confirmatory study is an enzyme immunoassay for C. difficile toxins A and B, with results available in two to four hours.] So in the real world, no doctor is going to wait around for that result before deciding whether to prescribe the Optimer drug, or the usual vancomycin…. They’re likely to prescribe fidaxomycin anyway, in the hopes that the patient is among the two-thirds of the population who will get a greater protection against relapse.”

“Whatever you say, say it with conviction,” said American author and humorist Mark Twain (1835 - 1910).

In an August 20 interview with Reuters, Optimer chief executive Michael Chang said he did not see potential fidaxomicin’s sales getting hurt by generic Vancocin — expected to hit the market by late 2009. Chang’s reasoning was that the first late-stage study of fidaxomicin showed a reduction in the number of patients who suffer a relapse of the infection, as compared with Vancocin. Chang identified the broad-spectrum antibiotic metronidazole, the common first-line treatment for the infection, as the chief competition.

Although C. difficile results in longer hospital stays (from three to thirteen days), both Chang and Prunty are gravely mistaken in assuming that doctors would be more inclined “to prescribe fidaxomicin anyway.” In the real world community hospitals are under tremendous pressure to rein in all costs. And, as drug procurement costs are visible and easy to quantify, one could just as easily conclude that hospital administrators would “encourage” treatment algorithms favoring generic vancomycin or metronidazole (off-label usage) — especially with potential Medicare reimbursement cuts on the horizon.

A second fidaxomicin Phase 3 clinical trial is ongoing, and Optimer anticipates reporting data from this trial later this year. Assuming this study demonstrates similar top-line results, fidaxomicin could be on hospital pharmacy shelves by mid-2010. Optimer expects fidaxomicin to have global peak sales potential of between $300 million and $600 million. However, until the company has data on fidaxomicin’s cost-effectiveness (calculated as total costs divided by proportion of successes), the drug will likely be reserved for use in vancomycin-resistant enterococci (VRE) infections — and track at the lower end of the company’s sales guidance.