BioWorld Today Contributing Writer
Excitement is building in advance of an FDA advisory committee meeting on Tuesday to review fidaxomicin, an antibiotic candidate being developed by Optimer Pharmaceuticals Inc. for Clostridium difficile infection (CDI).
Briefing documents released by the FDA showed fidaxomicin demonstrated noninferiority to vancomycin, with a positive impact on recurrence rates.
Optimer stock (NASDAQ:OPTR) gained 11 percent, or $1.30, on Friday to close at $13.13 on the expectation that the advisory committee will recommend approval.
"We have worked for eight years to see this moment. We are very encouraged," Optimer President and CEO Pedro Lichtinger told BioWorld Today. He credited the FDA's continuous marketing application (CMA) pilot program for the solidly positive briefing document issued by the FDA in preparation for its advisory committee meeting.
"We've been in contact almost every three weeks or four weeks, for years now," Lichtinger said. "You're never really surprised by emerging new thoughts, because you're part of the emerging new thoughts. We're very happy with that experience."
Optimer's fidaxomicin entered the FDA's Pilot 2 CMA program under its anti-infective division. The CMA concept was a goal of the Prescription Drugs User Fee Act of 1992. The Pilot 1 and 2 programs, enrolling a limited number of companies and fast-track drugs, allow much more extended interaction between the FDA and the company making an application. "I would hope that these type of programs are expanded so that companies can work with the FDA in a collaborative fashion," Lichtinger said.
The FDA's documents described two double-blind, randomized clinical trials carried out by Optimer, designated 101-1-C-003 and 101-1-C-004 in which 200-mg oral, twice-daily fidaxomicin was compared with 125-mg, oral, four-times daily vancomycin in patients with C. difficile-associated diarrhea. Clinical response was assessed on day 10 or 11 of therapy, with weekly checkups for 25 days after the last dose. Among subjects with a prior CDI episode and a recurrence within three months, fidaxomicin showed a 47 percent reduction in further recurrences as compared to Vancocin (vancomycin).
Fidaxomicin also improved the recurrence and global cure rate in patients with CDI who required concomitant antibiotics compared to Vancocin. The results were published in the Feb. 11, 2011, edition of The New England Journal of Medicine.
Further results from the second Phase III trial showed a clinically meaningful reduction in recurrence rates and higher global cure rates in the hyper-virulent BI/NAP1/027 and non-BI subgroups, compared to Vancocin. Fidaxomicin and Vancocin had similar cure rates in those subgroups.
The FDA's review largely supported Optimer's claims. Its documents noted: "Although the numbers we report are slightly different than those of the application, our final conclusions are in agreement with the applicant regarding noninferiority of fidaxomicin to vancomycin for the endpoint of clinical cure and superiority of fidaxomicin to vancomycin for the endpoint of global cure."
The briefing documents hinted that the Anti-infective Advisory Committee will recommend fidaxomicin for approval on Tuesday, and speculation on that outcome has begun. Cannacord Genuity Analyst George Farmer wrote, "Going into an upcoming FDA advisory committee meeting on Tuesday, we maintain our BUY rating on OPTR given our view of high likelihood of support for the company's lead drug, fidaxomicin, for treatment of C. diff. infection."
A final decision on approval of fidaxomicin would be due May 30. If granted, it would become the first new oral antibiotic for C. difficile in more than 25 years.
The CDC has a reported rate of 500,000 cases of CDI annually, and according to Lichtinger, many experts estimate that undiagnosed cases push that number up to 3 million. The incidence of CDI has increased in the U.S. in recent years, with the spread of the infection becoming a significant problem in hospitals and long-term care facilities. It also is becoming more prevalent in the community, although as a less severe infection.
The 2008 National Prevalence Study of Clostridium difficile in U.S. Healthcare Facilities the largest, most comprehensive nationwide study of the prevalence of C. difficile in U.S. health care facilities indicated that 13 of every 1,000 inpatients were either infected or colonized with the bacterium. Patients typically develop CDI from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal flora, allowing C. difficile bacteria to flourish.
ViroPharma Inc.'s Vancocin is the only antibiotic approved in the U.S. to treat infections caused by C. difficile, with other drugs, like metronidazole, being used off-label.
However, up to 30 percent of CDI patients treated with vancomycin or other drugs experience a recurrence of the disease. An additional approved antibiotic could give physicians another tool to fight the infection.
On the strength of its clinical data, Optimer licensed rights to fidaxomicin to Astellas Pharma Europe Ltd. in February for $68 million up front, supplementing its existing $59 million balance. The deal includes regulatory and commercial milestones up to $156 million, for a potential deal total of $224 million. The agreement gives Astellas rights to market fidaxomicin in Europe, where Optimer has a marketing authorization application pending, as well as the Middle East, Africa and the Commonwealth of Independent States. (See Bioworld Today, Feb. 8, 2011.)
Shortly after, Optimer supplemented its cash with an underwritten public offering of 6.9 million shares of common stock. The offering, fully exercised by underwriters, totaled $77.6 million, with shares priced at $11.25. (See BioWorld Today, Feb. 14, 2011.)
Fidaxomicin, a macrolide antibiotic, and Optimer's other pipeline antibiotic Pruvel, a fluoroquinolone, are small-molecule drugs, but the company also develops carbohydrate-based biologics based on its One-Pot Synthesis (OpopS) platform.
OPT-822/821 is a breast cancer antigen, Globo H, linked to a protein carrier that Optimer's subsidiary, OBI, is developing for metastatic breast cancer, originally licensed from the Memorial Sloan-Kettering Cancer Center. MSKCC has completed Phase I safety studies in prostate and breast cancer, and in January OBI began Phase II/III trials.
Optimer also has a new antibiotic, CEM-101 (previously OP-1068), targeted against bacteria that are resistant to macrolide and ketolide antibiotics, developed with its glyco optimization technology that has had some positive results in animal trials.