Novel Antibiotics: Kryptonite for Superbugs
The market for hospital-treated infections—including nosocomial pneumonia, skin infections, and urinary tract infections,
among others—will increase from $3.3 billion in 2010 to $4 billion in 2020, according to Decision Resources. In the case of
pneumonia, for which a broad armamentarium of treatments exists, the infection remains the seventh-leading cause of death
in the US.
Existing foils for the superbug include Cubist's Cubicin (daptomycin), a drug Cubist cannily licensed to Teva, in exchange
for the resolution of a patent dispute; Cubicin will now resist generic challengers through June of 2017. Revenues will help
support late-stage candidates like CXA-201, a Phase III drug acquired through Cubist's buyout of Calixa Therapeutics in 2009.
CXA-201 is being tested for complicated urinary tract infections (cUTI), and as a first-line intravenous therapy for gram-negative
bacterial infections, including multi-drug resistant pseudomonas aeruginosa. For cUTI, the company made the gutsy decision
to test against levofloxacin, or generic Levaquin, as a comparator. Levaquin had blockbuster sales in 2010, but lost patent
protection this year. "Cubist is banking very heavily on CXA-201," says Selvaraju.
Another class of antibiotics getting lots of attention is the oxazolidinones, of which Pfizer's Zyvox is a member. Despite
some overzealous selling techniques—Pfizer acknowledged "certain improper actions" related to Zyvox promotion as part of the
company's humongous $2.3 billion settlement over off-label Bextra marketing in 2009—the drug had blockbuster sales in 2010.
Trius Therapeutics, a San Diego-based biopharma, is now in Phase III testing on a next-in-class oxazolidinone called tedizolid
phosphate, or TR-701. If approved, Bayer will sell the drug outside the US. "Data [on TR-701] is coming in early 2012, and
I'm very confident that it will be positive," says Selvaraju. "There's activity in this drug not only in skin infections,
but also in bacterially associated pneumonia, so it's got a broad spectrum of activity, and I think it will become a very
nice commercial opportunity for Trius going forward."
A third member of the oxazolidinones class is Rib-X's Radezolid, which is a little bit further behind TR-701, with Phase III
data scheduled for early 2013. Rib-X formed a collaboration with Sanofi to explore bacterial ribosomes as a weapon against
superbugs; Selvaraju says Rib-X has a "very unique discovery platform" based on in-depth knowledge of the bacterial ribosome.
Lastly, Cempra Pharmaceuticals is in Phase III with a next-gen oral and intravenous fluoroketolide called solithromycin, a
member of the macrolides class of drugs. Macrolides include some of the most widely used agents for treating pneumonia and
skin infection, such as Pfizer's Zithromax. Many of the macrolides have gone generic, and solithromycin "appears to have none
of the side effect issues [of other macrolides], but does have a much greater activity against resistant organisms than any
other member of its class," says Selvaraju.