Johnson &
Johnson's swift exit from its collaboration with
Basilea for Zevtera (ceftobiprole) is
only the latest setback for the antibacterial field,
which has had little success in producing NME
approvals in recent years.
J&J
terminated its license after FDA's December 2009
"complete response" letter was followed Feb. 19 by a
negative opinion by the European Committee for
Medicinal Products for Human Use. Both regulatory
agencies pointed to data integrity problems with the
NDA; FDA said two new well-controlled trials would be
needed.
Basilea is not
taking J&J's exit lying down. The company has
requested arbitration, pointing to the deficiencies
FDA identified in J&J's conduct of the clinical
trial program. Ceftobiprole also received a "complete
response" letter in November 2008 that cited data
integrity problems with the clinical
trials.
Data integrity
issues have been a persistent problem in the
antibiotic field, starting with the
Ketek disaster (The RPM Report,
March 2008). But a bigger
issue for antibacterial R&D has been FDA's
evolving standards for non-inferiority trials.
Numerous antibiotic submissions have been referred
for additional clinical work (Pharmaceutical
Approvals Monthly, September
2009). So, despite
several applications coming in to FDA, Theravance's
Vibativ (telavancin) was the first
antibiotic NME approved in two years
(Pharmaceutical
Approvals Monthly, January
2009).
Given
ceftobiprole's action letter, hope for a 2010
approval letter in the antibacterial NME field rests
on Forest's ceftaroline.
Like
ceftobiprole, ceftaroline is a cephalosporin seeking
an indication for complicated skin and skin structure
infections. Forest's NDA also seeks indications in
community-acquired bacterial pneumonia and
methicillin-resistant Staphylococcus aureus infection
('The Pink Sheet'
DAILY, Jan. 19, 2010).
Forest's
long-term plans for ceftaroline include a combination
with a beta lactamase inhibitor, NXL-104, that
increases the range of susceptible pathogens "by
overcoming the most common resistant mechanism
utilized by many Gram negative bacteria." Dirk Thye,
president of Forest subsidiary Cerexa, said during a
Jan. 7 pipeline review. "We anticipate moving [the
ceftaroline/NXL-104 combo] into Phase II in the
second half of 2010."
Ceftaroline
"easily achieved non-inferiority" in cSSSI trials,
Thye reported, and response rates in MRSA, MSSA, and
strep were "very high" and comparable to the
comparator. In CABP, however, he called the results
"important and remarkable" because "when you pool the
results from the two studies, ceftaroline is
statistically superior to ceftriaxone."
Additionally,
Thye said, "the safety profile of ceftaroline is very
good. ... Cephalosporins have been used for decades
and are known to be quite safe."
- Bridget
Silverman
([email protected])
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