Use of Extended-Pulsed Regimen with DIFICLIR[TM] (fidaxomicin) is More Effective Than Standard vancomycin in Achieving Sustained Cure of Clostridium difficile Infection (CDI) and Preventing Recurrence

Vienna (ots/PRNewswire) -

CDI, a potentially fatal disease,[2] is three times as deadly as
MRSA[3],[4] and is estimated to cost the EU EUR3 billion per annum[5]

New data presented today at the 27th European Congress of Clinical
Microbiology and Infectious Diseases (ECCMID) 2017, demonstrate
benefits of extended-pulsed fidaxomicin (EPFX), compared to standard
vancomycin.[1] Data from the EXTEND study[1] show that EPFX provides
a superior rate of sustained clinical cure at 30 days following
treatment compared to standard vancomycin.[1] At 40 days, recurrence
rates were also found to be almost 10 times lower in patients treated
with EPFX compared with standard vancomycin.[1] EPFX is currently not
an approved dosing regimen.[6]

"The results of the study show at 30 days after end of treatment
(i.e. day 55 for extended fidaxomicin (EPFX) and day 40 for
vancomycin), recurrence occurred in 4.0% and 16.8% of patients
receiving EPFX and vancomycin, respectively", commented study author
Professor Benoit Guery, Infectious Diseases Services, University
Hospital of Lausanne. "The EXTEND study shows superiority of extended
fidaxomicin over vancomycin[1] and importantly this result is
obtained with the same number of tablets and therefore does not
change the cost and clearly improves the cost-efficacy ratio." The
extended-pulsed fidaxomicin regimen means that patients receive the
same number of tablets as the standard licensed course of fidaxomicin
(one tablet administered twice-daily for 10 days), but over a longer
period of time.

A randomised, controlled, open-label study, the EXTEND trial is
the first multicentre study of clinical outcomes for EPFX and was
conducted in hospitals in 22 European countries.[1],[7] 356 patients
aged 60 years or older with CDI were randomised (1:1) to receive
fidaxomicin 200mg oral tablets, twice-daily on days 1 to 5, then
once-daily on alternate days on days 6 to 25, or vancomycin 125mg
oral capsules, four-times daily on days 1 to 10.[1] EPFX dosing was
specifically designed to maintain efficacy in treating C. difficile
bacteria, while maximising preservation of gut flora through
alternate day dosing. This methodology allowed for an accurate
assessment of the benefits of extended, rather than increased, use of
fidaxomicin. The regimen was tested in an in vitro gut model at the
University of Leeds prior to use in this study.[8]

At 30 days after end of treatment, sustained clinical cure was
significantly higher for EPFX dosing compared with standard
vancomycin (70.1% [95% confidence interval (CI) 63.3-76.8] versus
59.2% [CI 52.0-66.4], p=0.03).[1] CDI recurrence rates were
significantly lower for EPFX than standard vancomycin: day 40, 1.7%
versus 16.8%; day 55, 4.0% versus 17.9%; day 90, 6.2% versus 19.0%;
all p<0.001.[1] Both treatment regimens presented similar safety
profiles.[1]

Dr. Andreas Karas, Senior Medical Director, Astellas Pharma EMEA,
commented, "Recurrence of disease is one of the largest ongoing unmet
needs of CDI treatment and the EXTEND study was designed to
specifically get this as low as possible by minimising the impact on
the gut flora by using a pulsed dosing regimen. Getting recurrence to
levels as low as shown in this trial is a positive outcome for
patients but also for health systems that bear the economic burden".

Economic analyses of the EXTEND study data indicate that EPFX is a
cost-effective treatment strategy compared with standard
vancomycin.[9] This finding was driven by the reduction in
hospitalisation costs, resulting from the reduced recurrence rates
associated with EPFX.[9]

Fidaxomicin is indicated in adults for the treatment of CDI. The
recommended dose is one 200mg tablet administered twice-daily for 10
days. Extended-pulsed regimen with fidaxomicin is not currently
approved.[6]

About Clostridium difficile infection

Clostridium difficile infection (CDI) is a recurring and
preventable bacterial infection of the colon that causes severe and
potentially deadly diarrhoea.[2],[10],[11] C. difficile bacteria are
naturally present in the gut of up to 3% of healthy adults, usually
without any problems. This is because the colonising C. difficile
bacteria are 'kept under control' by the 'good bacteria'.[11] An
alteration in the balance of the gut microflora, often caused by
broad-spectrum antibiotics, can reduce the number of 'good' bacteria,
allowing C. difficile to multiply and cause inflammation, severe
diarrhoea and potentially life-threatening complications.[10],[11]
CDI is one of the top ten hospital-acquired infections (HAIs) in
European hospitals[12] and is estimated to be three times as deadly
as MRSA.[3],[4] People in hospital with CDI are up to three times
more likely to die in hospital (or within a month of infection) than
those without CDI.[13],[14] Recurrence has been identified by the
European Society of Clinical Microbiology and Infectious Diseases
(ESCMID) as the most important problem in the treatment of CDI,[15]
and occurs in up to 25% of patients within 30 days of initial
treatment with broad-spectrum antibiotics.[16],[17],[18]

About DIFICLIR[TM] (fidaxomicin)

DIFICLIR[TM] is a macrocyclic antibiotic indicated for the
treatment of Clostridium difficile infection in adults;[6],[19] it is
targeted to kill the C. difficile bacteria[20] while sparing the
'good' bacteria in the gut that are important to protect against
recurrent disease.[21],[22],[23] The safety profile of DIFICLIR[TM]
is based on data from 564 patients with CDI treated with fidaxomicin
in Phase III studies.[24] The European Society of Clinical
Microbiology and Infectious Diseases (ESCMID) guidelines recommend
DIFICLIR[TM] as a first line therapy option in CDI patients at risk
of recurrence and in patients with severe and non-severe CDI.[25]

About the EXTEND study

A phase IIIb/IV trial, EXTEND is the first multicentre study of
clinical outcomes for extended-pulsed fidaxomicin. EXTEND is a
randomised, controlled, open-label study conducted in hospitals in 22
European countries. The primary objective of the study was to
evaluate whether EPFX was superior to standard vancomycin therapy for
sustained clinical cure of CDI 30 days after end of treatment.[1]

The study was initiated and sponsored by Astellas Pharma EMEA.

About Astellas Pharma EMEA

Astellas Pharma EMEA operates in 40 countries across Europe, the
Middle East and Africa, and is the EMEA regional business of
Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company
dedicated to improving the health of people around the world through
the provision of innovative and reliable pharmaceuticals. The
organisation's focus is to deliver outstanding R&D and marketing to
continue growing in the world pharmaceutical market. Astellas
presence in Europe also includes an R&D site and three manufacturing
plants. The company employs over 4,500 people across the EMEA region.
In 2013 Astellas was awarded SCRIP Pharmaceutical Company of the Year
in recognition of its commercial success and pipeline development.

References

1. Guery B, et al. Randomised, controlled, open-label study
comparing the efficacy of extended-pulsed fidaxomicin (EPFX) with
vancomycin therapy for sustained clinical cure of Clostridium
difficile infection in an older population: the EXTEND study.
Abstract presented at ECCMID 2017.

2. Ananthakrishnan AN. Clostridium difficile infection:
epidemiology, risk factors and management. Nat Rev Gastroenterol
Hepatol. 2011;8:17-26.

3. Bauer MP, et al. Clostridium difficile infection in Europe: a
hospital-based survey. Lancet. 2011;377:63-73.

4. European Centre for Disease Prevention and Control/European
Medicines Agency (ECDC/EMEA). Joint technical report The bacterial
challenge: time to react. Stockholm: ECDC / EMEA; 2009. Available
from: http://ecdc.europa.eu/en/publications/Publications/0909_TER_The
_Bacterial_Challenge_Time_to_React.pdf (last accessed April 2017).

5. Kuijper EJ, et al. ESCMID study group for Clostridium
difficile. Emergence of Clostridium difficile associated disease in
North America and Europe. Clin Microbiol Infect. 2006;12:2-18.

6. DIFICLIR Summary of Product Characteristics (SmPC) for European
Union, 2016.

7. Guery B, et al. Randomised, controlled, open-label study
comparing the efficacy of extended-pulsed fidaxomicin (EPFX) with
vancomycin therapy for sustained clinical cure of Clostridium
difficile infection in an older population: the EXTEND study.
NCT02254967 study information. Available from:
https://clinicaltrials.gov/ct2/show/NCT02254967 (last accessed April
2017).

8. Chilton CH, et al. Successful treatment of simulated
Clostridium difficile infection in a human gut model by fidaxomicin
first line and after vancomycin or metronidazole failure. J
Antimicrob Chemother. 2014;69(2):451-62.

9. Watt M, et al. Cost-effectiveness of extended-pulsed
fidaxomicin (EPFX) versus standard vancomycin (SV) in older patients
with Clostridium difficile infection in England. Abstract presented
at ECCMID 2017.

10. McMaster-Baxter NL, Musher DM. Clostridium difficile: recent
epidemiologic findings and advances in therapy. Pharmacotherapy.
2007;27:1029-39.1.

11. Sunenshine R, McDonald L. Clostridium difficile-associated
disease: new challenges from an established pathogen. Cleve Clin J
Med. 2006;73:187-97.

12. European Centre for Disease Prevention and Control (ECDC).
Point prevalence survey of healthcare-associated infections and
antimicrobial use in European acute care hospitals 2011-2012.
Stockholm, 2013. Available from: http://ecdc.europa.eu/en/publication
s/Publications/healthcare-associated-infections-antimicrobial-use-PPS
.pdf (last accessed April 2017).

13. Oake N, et al. The effect of hospital-acquired Clostridium
difficile infection on in-hospital mortality. Arch Intern Med.
2010;170:1804-10.

14. Hensgens MP, et al. All-Cause and disease-specific mortality
in hospitalized patients with Clostridium difficile infection: a
Multicenter Cohort Study. Clin Infect Dis. 2013;56:1108-16.

15. Bauer MP, et al. European Society of Clinical Microbiology and
Infectious Disease (ESCMID): treatment guidance document for
Clostridium difficile-infection (CDI). Clin Microbiol Infect.
2009;15:1067-79.

16. Johnson S, et al. Vancomycin, Metronidazole, or Tolevamer for
Clostridium difficile Infection: Results From Two Multinational,
Randomized, Controlled Trials. Clin Infect Dis. 2014;59(3):345-54.

17. Lowy I, et al. Treatment with monoclonal antibodies against
Clostridium difficile toxins. N Engl J Med. 2010;362;3:197-205.

18. Louie TJ, et al. Fidaxomicin versus vancomycin for Clostridium
difficile infection. N Engl J Med. 2011;364:422-31.

19. Mullane KM, Gorbach S. Fidaxomicin: first-in-class macrocyclic
antibiotic. Expert Rev. Anti Infect. Ther. 2011;9(7):767-777.

20. Babakhani F, et al. Killing kinetics of fidaxomicin and its
major metabolite, OP 1118, against Clostridium difficile. J Med
Microbiol. 2011;60:1213-7.

21. Finegold SM, et al. In vitro activities of OPT-80 and
comparator drugs against intestinal bacteria. Antimicrobial agents
and chemotherapy. 2004;48:4898-902.

22. Tannock GW, et al. A new macrocyclic antibiotic, fidaxomicin
(OPT-80), causes less alteration to the bowel microbiota of
Clostridium difficile-infected patients than does vancomycin.
Microbiology. 2010;156:3354.

23. Louie TJ, et al. OPT-80 eliminates Clostridium difficile and
is sparing of bacteroides species during treatment of C. difficile
infection. AAC. 2009;53:261-263.

24. Weiss K, Allgren RL, Sellers S. Safety analysis of fidaxomicin
in comparison with oral vancomycin for Clostridium difficile
infections. Clin Infect Dis. 2012;55(S2):S110-15.

25. Debast SB, et al. European Society of Clinical Microbiology
and Infectious Diseases (ESCMID): update of the treatment guidance
document for Clostridium difficile infection (CDI). Clin Microbiol
Infect. 2014:20(s2):1-26.

April 2017

AI/17/0001/CB

ots Originaltext: Astellas Pharma EMEA
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Josie Fisher
Ruder Finn
jfisher@ruderfinn.co.uk
Tel: +44(0) 20-7438-3068

Astellas Pharma EMEA Press Office
Tel: +44(0)7919-302-926

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