Colorectal cancer drugs:

Colon, or colorectal, cancer is cancer
that starts in the large intestine (colon)
or the rectum (end of the colon).


ZALTRAP FROM REGENERON AND
SANOFI  IS POTENTIALLY THE FIRST
NEW DRUG IN 5 YEARS
In the Phase III Velour trial, adding
Zaltrap (aflibercept) to a FOLFIRI
regimen improved overall survival
18.3% vs. placebo  and progression-
free survival 24.2% vs. placebo  in
patients with metastatic colorectal
cancer  previously treated with
oxaliplatin.

Zaltrap looks like a very interesting
concept, one which may fill an unmet
need for patients who have K-ras-
mutation-positive mCRC.  Estimated
approval: 2012.

Zaltrap represents a completely
new class of cancer drugs—the
recombinant-fusion-protein. Data
suggest it has potential in second line
where the most commonly used drug,
BMS/Lilly’s Erbitux, should not be used
in some patients with K-ras mutation.

Zaltrap can be used regardless of
patients’ K-ras  mutation status,
opening up the possibility for a further
targeted  second-line therapy.

This could be the first new colorectal
cancer therapy in five  years.





REGORAFENIB FROM BAYER HAS
SMALLISH SURVIVAL BENEFIT
Regorafenib is a structurally distinct
oral tyrosine kinase inhibitor with
inhibitory activity against several
kinases, including VEGFR2,3, KIT,
TIE2, PDGFR, FGFR, and BRAF.

Regorafenib is a once-daily pill that
works by blocking several molecular
pathways that cancer cells use to grow
and feed off the body's blood supply.
Regorafenib was designed to be an
improved version of Nexavar, the
kidney and liver cancer drug originally
developed by Onyx that was partnered
with Bayer.

Like Nexavar, regorafenib doesn't
shrink tumors much at all. Instead, the
drug appears to benefit patients by
putting tumors into stasis (a period  of
inactivity or equilibrium), which then
helps patients live a bit longer.

The phase III study enrolled 760 colon
cancer patients who were no longer
responding to currently approved
treatments. The patients were
randomized to receive regorafenib plus
best supportive care or best
supportive care plus a placebo.

After a second interim analysis,
patients treated with regorafenib
demonstrated a median overall
survival of 6.4 months compared to 5
months for patients treated with best
supportive care. The relative risk of
death was reduced by 23% following
regorafenib treatment.

Regorafenib did not shrink tumors
significantly more than best supportive
care, nor did the drug delay the time
before tumors started growing again.
"It's a modest benefit but a benefit
nonetheless," said Onyx spokesperson
Lori Melancon. "We believe the results
are clinically meaningful because
these are patients in the last line of
therapy who have no other treatment
options."

Approximately 15,000 colon cancer
patients in the U.S. and Europe no
longer respond to treatment with
several drugs including Roche's
Avastin, Eli Lilly's  Erbitux and Amgen's
Vectibix and will therefore be eligible
for further therapy with regorafenib.

Bayer, in a recent investor
presentation, said regorafenib could
generate $1 billion in revenue based
on possible approvals in multiple
cancer types including colon cancer
and GIST, or stomach, cancer.





PERIFOSINE TESTED FOR
COLORECTAL CANCER
In April 2012 Keryx Pharmaceuticals
announced  the failure of its
experimental colon cancer drug
perifosine.

Keryx Biopharmaceuticals, Inc.was
running a Phase 3 clinical trial for KRX-
0401 (perifosine), the Company's
novel, potentially first-in-class, oral anti-
cancer agent that inhibits Akt
activation in the phosphoinositide 3-
kinase (PI3K) pathway, for the
treatment of patients with refractory
advanced colorectal cancer.

The Phase 3 trial, entitled the "X-
PECT" (Xeloda(R) + Perifosine
Evaluation in Colorectal cancer
Treatment) trial, is a randomized (1:1),
double-blind trial comparing the
efficacy and safety of perifosine +
capecitabine vs. placebo +
capecitabine in approximately 430
patients with refractory advanced
colorectal cancer.




TROVAX VACCINE TESTED FOR
COLORECTAL CANCER
An appealing target  is a protein called
5T4. 5T4 is made in high amounts by
many different types of cancers
(colorectal, ovarian, gastric, and
kidney) but only rarely in other cells,
and is believed to be involved in
cancer metastasis. Oxford BioMedica,
a United Kingdom-based
biopharmaceutical company,
developed a cancer vaccine to target
5T4 called TroVax. TroVax delivers the
blueprints for 5T4 in a modified
(benign) virus, just like a typical
vaccine, the aim being to stimulate an
immune response against the 5T4
protein.
In phase II clinical trials, TroVax was
tested in more than 200 patients and
95 percent showed “potent and
sustained immune responses” with
minimal side effects. Phase III clinical
trials started in 2008, but underwent a
series of amendments recommended
by the FDA. The FDA is currently
reviewing the data collected so far to
recommend possible guidance for
approval. Clinical trials have been
testing the efficacy of TroVax to treat
kidney and prostate cancers as well.


OTHER DEVELOPMENTS
ERBITUX
Erbitux by Eli Lilly and Merck KGaA
Erbitux works in around 60% of the two-
thirds of bowel cancer patients who
have a cancer gene called K-RAS wild
type.