DIFICID(TM) (fidaxomicin), a first-in-class antibiotic, now approved in Canada to treat C. difficile, a serious and life-threatening infection
TORONTO, July 5, 2012 /CNW/ – Optimer Pharmaceuticals Canada, Inc.
announced today the approval of DIFICID (fidaxomicin) by Health Canada
for the treatment of Clostridium difficile infection (CDI) in patients 18 years of age and older. DIFICID was
approved in Canada on a priority basis recognizing the critical need
for new options to treat this disease and is the first new treatment
for CDI in over 20 years.
Two large double-blind, comparative, randomized clinical studies were
conducted with results published in two leading medical journals, The New England Journal of Medicine and The Lancet Infectious Diseases. Over 400 Canadian patients participated in the trials, representing
over one third of patients studied. DIFICID was superior to oral
vancomycin in reducing CDI recurrence by 46% and shown to be superior
in sustaining clinical response for 28 days after treatment(i,ii).
DIFICID is the first in a new class of antibiotics called macrocycles.
DIFICID targets C. difficile with a high degree of specificity, and has been shown to preserve the
normal gut flora, suppress the production of C. difficile toxins A and B, and inhibit the production of C. difficile spores(i). “Collectively, these novel effects may contribute to DIFICID’s
superior efficacy in reducing the risk of CDI recurrence,” stated Dr.
Wendy Arnott, Executive Director, Scientific Affairs, Optimer Canada.
CDI has a significant burden on the healthcare system(iii,iv,v,vi )and on the lives of patients and their families suffering from this
“Clostridium difficile infections (CDI) have been an increasing
challenge and burden for the Canadian healthcare system during the last
decade(vii,viii,ix), and affect the elderly population in a disproportionate manner,(iv,v,vii,x )” said Dr. Karl Weiss, Professor of Medicine at Maisonneuve-Rosemont
Hospital and a member of the Faculty of Medicine at UniversitÃ© de
MontrÃ©al. “Reducing CDI recurrence is a major objective, knowing that
20 to 30% of affected Canadian patients will experience at least one
relapse of the disease, escalating to over 60% after multiple
“Today marks a significant advance in the fight against CDI. Awareness
of the burden of CDI on the Canadian healthcare system is high with
many healthcare providers, patients, and caregivers impacted by this
devastating infection, but what is less commonly understood is that CDI
is much more than an acute infection. In a significant proportion of
patients it is a chronic disease given this high rate of recurrence,”
said Paulash Mohsen, President and Country Manager for Optimer Canada.
“We are proud to have the opportunity to bring this first-in-class
antibiotic to help Canadian patients in need.”
“C. difficile can be a very serious condition with devastating impact on the lives of
patients and their caregivers,” said Gail Attara, President & Chief
Executive Officer, Gastrointestinal Society. “Advances in CDI therapy
are important if we want to win the ongoing battle against these types
About CDI in Canada
CDI is one of the leading causes of hospital-acquired infections(iii,vi,xi), and mortality has been reported to be as high as 17% during outbreaks
in Canada(ix). C. difficile is a virulent, toxin- and spore-producing pathogen. Infection from
this pathogen is a serious and life-threatening condition which can
result in severe and debilitating diarrhea, removal of the colon and,
in the most serious cases, death(iv,v,viii,xii). CDI predominantly affects hospital inpatients(v,viii,ix,x )and has been associated with numerous outbreaks across the country(ix). The risk of CDI increases with age, an impaired immune system,
co-morbid disease and previous exposure to antibiotics which disrupt
the patient’s normal gut flora(v,x,xiii,xiv).
CDI represents a major challenge to the Canadian healthcare system(iii,vi,ix).( )The detriment of this disease impacts the lives of the patients and the
families of those who suffer from this virulent pathogen. In Canada,
the infection has been associated with a median increase in length of
stay in the hospital of 6 days(xv). The spore form of pathogen is resistant to gastric acid(xvi,xvii,xviii), antibacterial soaps and alcohol based hand sanitizers(xix), and can survive for months on surfaces(xix). While not as well characterized, CDI is thought to be an increasing
burden in long-term care facilities(xx,xxi,xxii,xxiii,)( )and the community setting as well(xii,xxiv).
Two pivotal, randomized, multi-center, double-blinded trials were
conducted in a total of 1,164 adults with confirmed CDI. A
non-inferiority design was utilized to demonstrate the efficacy of
DIFICID (200 mg orally twice daily for 10 days) compared to vancomycin
(125 mg orally four times daily for 10 days) for initial cure of the
infection. Additional efficacy endpoints were recurrence of infection
and sustained clinical response, defined as clinical response at the
end of treatment and not having a recurrence of CDI at any time through
28 days beyond the end of treatment.
DIFICID was superior to oral vancomycin in reducing CDI recurrence by
46% (recurrence rates 14.1% and 26.0% for DIFICID and vancomycin
respectively p<0.001). DIFICID was also shown to be superior to
vancomycin in sustaining clinical response for 28 days after treatment(i,ii). For treatment of the acute initial episode DIFICID achieved the goal
of noninferiority versus vancomycin [95%CI](i,ii).
DIFICID was approved by the FDA in May 2011, and by the European
Medicines Agency (EMA) in December 2011.
Important Safety and Dosing Information about DIFICID(xxv)
DIFICID should not be used for systemic infections. DIFICID should be
used only to treat infections that are proven or strongly suspected to
be caused by C. difficile.
The most common adverse drug reactions in patients receiving DIFICID
were nausea (2.7%), constipation (1.2%), and vomiting (1.2%). The
majority of adverse drug reactions were reported as mild or moderate in
DIFICID is administered orally over a 10 day course at 200mg twice
daily, and its activity is confined to the gastrointestinal tract,
where CDI persists, allowing for maximum bactericidal activity.
Video footage of Dr. Karl Weiss, clinical investigator on the
comparative trials published in NEJM and The Lancet Infectious Diseases
is available for download at http://cnw.pathfireondemand.com/viewpackage.action?packageid=558
For complete Product Monograph for DIFICID, please call 1-855-DIFICID
Optimer Pharmaceuticals Canada Inc. is an indirect wholly-owned
subsidiary of Optimer Pharmaceuticals, Inc. (NASDAQ: OPTR), a
biopharmaceutical company focused on discovering, developing and
commercializing innovative hospital specialty products that have a
positive impact on society. Optimer has developed and commercialized
fidaxomicin tablets, an antibacterial drug authorized for sale as
DIFICID® in the US and as DIFICLIR(TM) in Europe for the treatment of adult patients with Clostridium difficile infection (CDI). Additional information can be found at http://www.optimerpharma.com.
Forward Looking Statements
Statements included in this press release that are not a description of
historical facts are forward-looking statements, including without
limitation statements related to Optimer’s plans to commercialize
DIFICID, the incidence of CDI, and Optimer’s plans to conduct
post-marketing research, a surveillance program and clinical trials of
DIFICID. Words such as “believes”, “would”, “anticipates”, “plans”,
“expects”, “may”, “intend”, “will”, and similar expressions are
intended to identify forward-looking statements. The inclusion of
forward-looking statements should not be regarded as a representation
by Optimer that any of its plans will be achieved. These
forward-looking statements are based on management’s expectations on
the date of this release. Actual results may differ materially from
those set forth in this release due to the risks and uncertainties
inherent in Optimer’s business including, without limitation, risks
relating to:, the ability of Optimer and its third party contractors to
manufacture and supply sufficient quantities of DIFICID in accordance
with Good Manufacturing Practices to meet demand, whether healthcare
professionals will prescribe DIFICID, whether DIFICID will receive
reimbursement coverage from healthcare payors and government agencies,
the extent to which DIFICID organization, Optimer’s ability to
initiate and complete planned post-marketing research, surveillance
programs and clinical trials of DIFICID in a timely manner and the
results of those efforts and other risks detailed in Optimer’s filings
with the Securities and Exchange Commission.
(i) DIFICID Product Monograph. June 2012, Optimer Pharmaceuticals Canada,
(ii) Based on a pooled analysis of the two pivotal Phase 3 clinical studies:
1) Cornely, O et al. “Fidaxomicin versus vancomycin for infection with
Clostridium difficile in Europe, Canada, and the USA: a double-blind,
non-inferiority, randomised controlled trial.” The Lancet Infectious Diseases 2012: 12(4):281-289. 2) Louie, T et al. “Fidaxomicin versus Vancomycin
for Clostridium difficile Infection.” N Engl J Med 2011;364:422-31.
(iii) Ghantoji, SS et al. Economic healthcare costs of Clostridium difficile
infection: a systematic review. J Hosp Infect. 2010 Apr: 74(4): 309-18.
(iv) McFarland LV et al. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. ICHE. 1999: 20(1): 43-50.
(v) O’Brien JA et al. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. ICHE. 2007: 28(11): 1219-1227.
(vi) Miller MA, Hyland M, Ofner-Agostini M, Gourdeau M, Ishak M. Morbidity,
mortality, and healthcare burden of nosocomial Clostridium difficile-associated diarrhea in Canadian hospitals. Infect Control Hosp Epidemiol 2002;23:137-40
(vii) Mulvey et al. Hypervirulent Clostridium difficile Strains in Hospitalized Patients, Canada. Emerg Infect Dis 2010; 16:678-81
(viii) Gravel et al. Health Care-Associated Clostridium difficile Infection in Adults Admitted to Acute Care Hospitals in Canada: A
Canadian Nosocomial Infection Surveillance Program Study. Clin Infect
Dis 2009; 46:568-76
(ix) Pepin et al. Mortality Attributable to Nosocomial Clostridium difficile-associated Disease During an Epidemic Caused By a Hypervirulent Strain
in Quebec. CMAJ. 2005;173(9):1-6.
(x) Kelly et al. Clostriodium difficile–More Difficult than Ever. N Engl J Med. 2008;359(18):1932-1940
(xi) Health Canada. It’s Your Health. June 2006. Catalogue #
H13-7/13-2006E-PDF, ISBN # 0-662-43588-5. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases-maladies/cdifficile-eng.php accessed May 31 2012.
(xii) Louie, T et al. N Engl J Med 2011;364:422-31.
(xiii) Bignardi GE. Risk factors for Clostridium difficile infection. J Hosp
Infect 1998; 40:1-15.
(xiv) Barbut F, Petit JC. Epidemiology of Clostridium difficile-associated
infections. Clin Microbiol Infect 2001;7:405-10.
(xv) Forster A, Taljaard M, Oake N, Wilson K, Roth V, van Walraven C. The
effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital. CMAJ 2012; 184(1) 37-42.
(xvi) Nerandzic M et al. Examination of Potential Mechanisms to Explain the
Association between Proton Pump Inhibitors and Clostridium difficile Infection. Antimicrob. Agents Chemother. 2009: 53(10):4133-7.
(xvii) Sunenshine RH, McDonald LC. Clostridium difficile-associated Disease: New Challenges from an Established Pathogen. Cleve Clin J Med. 2006:73(2):187-197.
(xviii) Jump RLP, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile Survives in Room Air on Moist Surfaces and in Gastric Contents with
Reduced Acidity: A Potential Mechanism to Explain the Association
Between Proton Pump Inhibitors and C. difficile-associated Diarrhea? Antimicrob Agents Chemother. 2007:51(8):2883-7.
(xix) Cohen SH et al. Clinical Practice Guidelines for Clostridium difficile infection in Adults: 2010 Update by the Society for Healthcare
Epidemiology of America (SHEA) and the Infectous Diseases Society of
America (IDSA). Infect Control Hosp Epidemiol. 2010:31(5):431-455
(xx) Simor A et al. Clostridium difficile in Long-Term-Care Facilities for the Elderly. Infection Control and Hospital Epidemiology. 2002:23(11):696-703.
(xxi) Walker KJ, Gilliland SS, Vance-Bryan K, Moody JA, Larsson AJ,
Rotschafer JC, et al. Clostridium difficile colonization in residents of long-term care facilities: prevalence and
risk factors. J Am Geriatr Soc 1993;41:940-6.
(xxii) Rivera EV, Woods S. Prevalence of asymptomatic Clostridium difficile colonization in a nursing home population: a cross-sectional study. J Gender-Specific Med 2003;6:27-30
(xxiii) Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN.
Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97-100
(xxiv) Kasper AM et al. A Multicenter Study of Clostridium difficile Infection-related Colectemy, 2000-2006. Infect Control Hosp Epidemiol. 2012 May;33(5):470-6
(xxv) Prescribing Information. May 2011, Optimer Pharmaceuticals, Inc.
SOURCE Optimer Pharmaceuticals Canada, Inc.