In a person with leukemia, the bone
marrow makes abnormal white blood
cells. The abnormal cells are leukemia

Unlike normal blood cells, leukemia
cells don't die when they should. They
may crowd out normal white blood
cells, red blood cells, and platelets.
This makes it hard for normal blood
cells to do their work.

In November 2011 the FDA  approved
Erwinaze (asparaginase Erwinia
chrysanthemi) to treat patients with
acute lymphoblastic leukemia (ALL),
who have developed an allergy
(hypersensitivity) to E. coli derived
asparaginase and pegaspargase
chemotherapy drugs used to treat ALL.

Erwinaze is made by EUSA Pharma, a
transatlantic specialty pharmaceutical
company based in  Langhorne, Pa, US
and Oxford, UK.

Acute lymphoblastic leukemia is a type
of cancer in which the bone marrow
makes too many lymphocytes, a type
of white blood cell. White blood cells
help the body fight infection and are
formed in the bone marrow.

Erwinaze is injected directly into the
muscle three times a week and works
by breaking down one of the body’s
protein building blocks (the amino acid,
asparagine) that is present in the
blood, and is necessary for the growth
of all cells. Leukemia cells cannot
produce this protein building block.

When a patient is treated with
Erwinaze the leukemia cells die.

Normal human cells are able to make
enough asparagine for their own
needs through biosynthesis and will
not be affected by treatment with

The safety and effectiveness of
Erwinaze was evaluated in a clinical
trial of 58 patients. Additional safety
data was collected from the Erwinaze
Master Treatment Protocol (EMTP), an
expanded access program that
enrolled 843 patients. Patients in both
studies were unable to continue
receiving pegaspargase or
asparaginase derived from E. coli due
to allergic reactions.

ALL is the most common form of
childhood cancer, with approximately
2,900 patients under the age of 20
diagnosed in the USA each year. It is
also one of the most curable forms of
cancer, with remission rates in treated
children of over 95% and 75 - 85%
surviving at least five years without
recurrence of leukemia. Treatment
involves a number of stages and
drugs, and typically includes
asparaginase as an essential
component of current protocols.

An estimated 15 - 20% of ALL patients
develop hypersensitivity to E. coli-
derived asparaginase, representing
approximately 450 - 600 children in the
United States each year

ERWINAZE is an asparaginase enzyme
that depletes the level of asparagine in
the bloodstream.  Asparagine is
essential for cell growth, and its
removal from the blood inhibits the
growth of cells associated with acute
lymphoblastic leukemia.  Asparaginase
products are derived from bacteria,
and approximately 15 - 20% of patients
develop hypersensitivity to modern
products derived from Escherichia coli,
preventing their continued treatment.  

ERWINAZE was originally discovered
by the UK Health Protection Agency.

In November 2011 Incyte Corporation  
announced the FDA has granted
marketing approval for Jakafi
(ruxolitinib) for the treatment of
patients with intermediate or high-risk
myelofibrosis (MF), including primary
MF, post-polycythemia vera MF and
post-essential thrombocythemia MF.

Patients with intermediate and high-
risk MF represent 80 to 90 percent of
MF patients. Jakafi (JAK-ah-fye) is the
first and only product to be approved
by the FDA for MF, and the first in a
new class of drugs, known as JAK
inhibitors, to be approved for any
indication. Jakafi is an oral JAK1 and
JAK2 inhibitor.

The FDA approval was based on
results from two randomized Phase III
trials (COMFORT-I and COMFORT-II),
which demonstrated that patients
treated with Jakafi experienced
significant reductions in splenomegaly
(enlarged spleen). COMFORT-I also
demonstrated improvements in
symptoms as measured by the
modified Myelofibrosis Symptom
Assessment Form (MFSAF) v.2.0
electronic diary and the MFSAF Total
Symptom Score (TSS) comprised of six
specific symptoms (abdominal
discomfort, pain under the left ribs, an
early feeling of fullness, night sweats,
bone and muscle pain and itching) all
of which contributed to the overall
benefit. Most patients taking placebo
experienced worsening of these same

Two randomized Phase III trials have
demonstrated that the Janus kinase
(JAK) inhibitor ruxolitinib from Incyte
improves response rates compared
with currently available therapies in
patients with MF.

The two trials, COMFORT-I and II, are
the first randomized drug trials for the
potentially deadly bone marrow
disorder that frequently leads to

“Data from the COMFORT studies
indicate that ruxolitinib has the
potential to significantly improve the
current treatment landscape for most
patients with MF,” said Alessandro
Vannucchi, MD, associate professor of
hematology at the University of
Florence in Italy, who led COMFORT-

MF is characterized by dysregulation
of JAK-STAT signaling, making this
pathway an attractive therapeutic
target. Ruxolitinib is an oral drug that
inhibits both JAK1 and JAK2 tyrosine
kinases. “There are no current
therapies that work for a sustained
period in MF,” Dr. Vannucchi said. “We
urgently need new treatments for this
condition.” He noted that patients with
MF responded within a few weeks of
being on ruxolitinib.

In December 2011 data presented  at  
American Society of Hematology  
Annual Meeting in San Diego, CA,
showed that Micromet’s blinatumomab
more than doubled the complete
remission rate produced by current
standard therapies used to treat adult
patients with relapsed or refractory B-
precursor acute lymphoblastic
leukemia (ALL).

In March 2012 Amgen has bought

Blinatumomab is the first of a new
class of agents called BiTE antibodies,
designed to harness the body's T cells
to kill cancer cells.

In this phase 2 single-arm dose-
ranging trial, 68% of evaluable patients
(17/25) across all tested doses and
schedules achieved a complete
response  following treatment with

Previously in a small, Phase 1 trial nine
of 12 patients on the drug reached
complete remission, with no evidence
of cancer cells in their bone marrow.

The trial  consists of patients with
acute lymphoblastic leukemia whose
disease has relapsed after standard
therapy. The cancer affects about
5,760 people in the U.S. each year.
There hasn't been a new medicine for
this indication approved in more than
three decades.

Blinatumomab (MT103) is a next-
generation monoclonal antibody-based
therapeutic designed to direct the
body's cell destroying T-cells against
target cells expressing CD19, a protein
expressed on the surface of B-cell
derived acute lymphoblastic leukemias
and non-Hodgkin's lymphomas.

Acute Lymphoblastic Leukemia (ALL)
is an aggressive cancer of the blood
and bone marrow. Patients with ALL
have abnormal white blood cells
(lymphocytes) that crowd out healthy
white and red blood cells and platelets,
leading to infection, anemia (fatigue),
easy bleeding and other serious
effects. 50%−60% 3,8 of patients will
relapse following frontline therapy.  

Standard chemotherapy is associated
with a mortality rate of up to 23%  The
average five-year survival rate for
adult ALL patients after first relapse is

In December 2011 Ariad
Pharmaceuticals highlighted improved
interim results from a  study of its
experimental leukemia drug ponatinib.

Following treatment with ponatinib,
47% of chronic myeloid leukemia
(CML) patients with chronic phase
disease had a major cytogenic, or
cellular, response, meaning a
reduction in the number mutated cells
to less than 35%. In the subgroup of
patients with the T315I mutation, the
major cytogenic response rate was

These are improved response rates
compared to ponatinib data released
from the same study in early November

The pivotal study of ponatinib, dubbed
PACE, enrolled 450 CML and ALL
patients, all of whom are either
resistant to Novartis'  Tasigna or
Bristol-Myers Squibb's  Sprycel, or who
have a specific genetic mutation known
as T315I that makes the leukemia
resistant to current therapies.

The data  come from an analysis of
392 patients with a median follow-up
time of almost six months. Ariad
expects the study to complete in the
first half of 2012.

Six percent of patients in the ponatinib
study developed pancreatitis,
inflammation of the pancreas, although
no patients withdrew from the study
due to the side effect. Four patients,
all with advanced CML and other
medical complications, died during the
study and may have been related to
ponatinib, researchers said.

Ponatinib is now in a pivotal Phase II
clinical trial as a treatment for patients
with chronic myeloid leukemia or
Philadelphia positive acute
lymphoblastic leukemia whose cancers
are resistant to Bristol-Myers Squibb's
Sprycel or Novartis's Tasigna.

Ponatinib is being developed to treat
chronic myeloid leukemia (CML) and
so-called Philadelphia-positive acute
lymphoblastic leukemia (ALL). Both
forms of cancer cause excessive and
unregulated production of white blood
cells by the bone marrow due to a
genetic abnormality that produces
excessive quantities of a protein known

In 2001, Novartis' Gleevec was
approved as one of the first "targeted"
drugs capable of repairing the genetic
error in CML and ALL patients.
Gleevec became a multi-billion dollar
blockbuster drug for Novartis, which
went on to develop and market a
successor drug, Tasigna. Bristol-Myers
Squibb markets a similar drug known
as Sprycel.

Ariad views ponatinib as the next step
in the evolution of targeted leukemia
drugs because the drug is engineered
to inhibit the production of BCR-ABL
protein even in patients who no longer
respond to Tasigna and Sprycel.

In December 2011 Pharmacyclics
showcased strong interim results from
its leukemia drug PCI-32765 just a few
days after licensing the drug to
Johnson & Johnson.

After 10 months of follow-up, 70% of
chronic lymphocytic leukemia patients
responded to a low-dose of PCI-
32765. That's an increase from a 48%
response rate reported last spring.

Patients treated with a higher dose of
PCI-32765 reported a 44% response
rate after a shorter 6.5 months of
follow up.

All patients enrolled in the PCI-32765
study have CLL that is no longer
responding to currently approved

In December 2011 Pharmacyclics
licensed PCI-32765 to Johnson &
Johnson for $150 million upfront and
as much as $825 million in future
development milestones.

PCI-32765 is a pill designed to block
the production of an enzyme known as
Bruton's tyrosine kinase that is
responsible for the unchecked or
cancerous growth of B-cells.

CytRx Corp. said a phase II proof-of-
concept study of bafetinib showed
clinical activity in patients with relapsed
or refractory B-cell chronic lymphocytic
leukemia or B-CLL. CytRx has also
determined the dose for moving into
any future clinical trials in combination
with a cytotoxic agent or monoclonal
antibody. Bafetinib, a Lyn kinase
inhibitor, targets a member of the B-
cell receptor activation pathway in a
manner similar to inhibitors of other
tyrosine kinases developed for B-CLL.

B-CLL is the most common form of
leukemia in adults in Western
countries. More than 17,000 new
cases of B-CLL are reported in the     
U.S. each year. Patients with high-risk
B-CLL have a median overall survival
of one to five years.

CytRx holds rights to bafetinib
(formerly known as INNO-406) in all
territories except Japan. Bafetinib was
originated by Kyoto, Japan-based
Nippon Shinyaku Co. Ltd.

In November 2008, CytRx announced
that bafetinib demonstrated clinical
responses in patients with CML in an
international, open-label Phase 1 dose-
ranging clinical trial conducted in
patients with CML and other leukemias
that have a certain mutation called the
Philadelphia Chromosome (Ph+) and
are intolerant of or resistant to
Gleevec and, in some cases, second-
line tyrosine kinase inhibitors such as
dasatinib and nilotinib.

CytRx's chief medical officer Daniel
Levitt, said," Bafetinib is 25 to 55 times
more potent than the protein-tyrosine
kinase inhibitor imatinib (Gleevec)
against certain BCR-ABL-positive
leukemia cell lines and is a potent
inhibitor of Lyn kinase, which is over
expressed in many imatinib-resistant
leukemia cells."

CytRx president and CEO Steven
Kriegsman said," We are currently in
discussions with potential partners to
further advance bafetinib's clinical
development as we focus our clinical
efforts on our other two promising drug
candidates, INNO-206 and

From CytRx Corporation,  a small
biopharmaceutical company
specializing in oncology, recently
announced that an advanced form of
acute promyelocytic leukemia, or APL,
has been eradicated in former NBA
player Ray Johnston following
treatment with CytRx's experimental
cancer drug tamibarotene.
Mr. Johnston was afflicted with a
particularly aggressive type of APL
called chloromas and had previously
failed other approved therapies. More
than 30 tumors were detected
throughout his body prior to treatment
with tamibarotene, which was
administered in tablet form on a
compassionate use protocol.

"Following four months of treatment
with tamibarotene, the disease was
totally eliminated," said Mr. Johnston.
"In January, my PET scan showed a
significant decrease in the disease,
and in April it confirmed that the
leukemia was completely gone. Last
week marked my six-month
anniversary of being cancer-free." Mr.
Johnston will continue taking orally
administered tamibarotene every other
month as an added measure given his
history of relapses.
Dr Collins, his doctor says:
"We wanted to give tamibarotene a try
for Ray given the fact that his APL has
relapsed several times following
treatment with all trans-retinoic acid
(ATRA), anthracycline chemotherapy
and arsenic trioxide (ATO), the current
first- and second-line therapies. There
currently is no approved third-line
therapy for APL," said Dr. Collins.
CytRx is conducting the Phase 2 STAR-
1 registration trial under a Special
Protocol Assessment to evaluate the
efficacy and safety of tamibarotene in
patients with third-line APL. In Japan,
tamibarotene was approved in 2005
and is marketed for the treatment of
second-line APL.

Tamibarotene is an orally available,
rationally designed, synthetic retinoid
compound that was developed to
potentially avoid toxic side effects of
ATRA by binding to its molecular target
more selectively than ATRA. CytRx
holds the North American and
European rights to tamibarotene as a
treatment for APL.
Trial no:NCT00520208

Two newer drugs, Sprycel and
Tasigna, beat out the groundbreaking
cancer drug Gleevec in treating people
with newly diagnosed chronic myeloid
leukemia (CML).
In separate studies, both newer drugs
were associated with substantially
better response rates compared with
the older Gleevec.
Sprycel is made  by Bristol-Myers
Squibb, Tasigna is by Novartis
The first study  randomly assigned 519
patients to Sprycel or Gleevec.
After a year, 77 percent of the patients
receiving Sprycel had a complete
cytogenetic response, compared with
66 percent of the patients receiving
Gleevec. Complete cytogenetic
response is the disappearance of all
the cancer cells from the bone marrow.
In the second report, Italian
researchers randomly assigned 846
patients to Tasigna or Gleevec.
After one year, more patients -- about
80 percent of those receiving Tasigna
-- had a complete cytogenetic
response, compared with 65 percent of
the patients receiving Gleevec.

National trial for children in the UK.
This large phase III trial is refining
treatments for children with acute
lymphoblastic leukemia (ALL). Most
children with ALL will be recruited onto
this trial as a standard part of their
treatment. The trial aims to reduce
treatment as much as possible while
still ensuring as many children as
possible are cured of ALL.
This national clinical trial is being run
by Dr Nick Goulden at Great Ormond
Street Hospital in London and Dr Pam
Kearns at Birmingham Children’s

Hematopoietic stem cell transplantation
(HSCT) is the transplantation of blood
stem cells derived from the bone
marrow  or blood.
Stem cell transplantation is a medical
procedure in the fields of hematology
and oncology, most often performed
for people with diseases of the blood,
bone marrow, or certain cancer.

With the availability of the stem cell
growth factors GM-CSF and G-CSF,
most hematopoietic stem cell
transplantation procedures are now
performed using stem cells collected
from the peripheral blood, rather than
from the bone marrow. Collecting
peripheral blood stem cells provides a
bigger graft, does not require that the
donor be subjected to general
anesthesia to collect the graft, results
in a shorter time to engraftment, and
may provide for a lower long-term
relapse rate.
Many recipients of HSCTs are multiple
myeloma or leukemia patients who
would not benefit from prolonged
treatment with, or are already resistant
to, chemotherapy.
Some  conditions that are  treated with
stem cell transplants include sickle-cell
disease,  neuroblastoma, lymphoma,
Ewing's Sarcoma  and Hodgkin's
More recently  so-called "mini
transplant," procedures have been
developed that require smaller doses
of preparative chemo and radiation.
This has allowed HSCT to be
conducted in the elderly and other
patients who would otherwise be
considered too weak to withstand a
conventional treatment regimen.

In August 2011 doctors at the
University of Pennsylvania said a
treatment made the most common type
of leukemia completely disappear in
two of the patients and reduced it by
70 percent in the third. In each of the
patients as much as five pounds of
cancerous tissue completely melted
away in a few weeks, and a year later it
is still gone.

The results of the preliminary test
“exceeded our wildest expectations,”
says immunologist Dr. Carl June a
member of the Abramson Cancer
Center's research team.

The Penn scientists targeted
chroniclymphocytic leukemia (CLL),
the most common type of the blood
disease. It strikes some 15,000 people
in the United States, mostly adults, and
kills 4,300 every year.

Chemotherapy and radiation can hold
this form of leukemia at bay for years,
but until now the only cure has been a
bone marrow transplant. A bone
marrow transplant requires a suitable
match, works only about half the time,
and often brings on severe, life-
threatening side effects such as pain
and infection.

In the Penn experiment, the
researchers removed certain types of
white blood cells that the body uses to
fight disease from the patients. Using a
modified, harmless version of HIV, the
virus that causes AIDS, they inserted a
series of genes into the white blood
cells.  These were designed to make to
cells target and kill the cancer cells.  
After growing a large batch of the
genetically engineered white blood
cells, the doctors injected them back
into the patients.

In similar past experimental treatments
for several types of cancer the re-
injected white cells killed a few cancer
cells and then died out. But the Penn
researchers inserted a gene that made
the white blood cells multiply by a
thousand fold inside the body. The
result, as researcher June put it, is that
the white blood cells became “serial
killers” relentlessly tracking down and
killing the cancer cells in the blood,
bone marrow and lymph tissue.

As the white cells killed the cancer
cells, the patients experienced the
fevers and aches and pains that one
would expect when the body is fighting
off an infection, but beyond that the
side effects have been minimal.

With results for the three  patients
published simultaneously in the New
England Journal of Medicine and
Science Translational Medicine, money
for further studies -- not just in this one
type of leukemia, but in other cancers
-- will likely pour in from both the
government and drug companies.

The treatment uses a form of white
blood cells called T cells harvested
from each patient. A manmade virus-
like vector is used to transfer special
molecules to the T cells. One of the
molecules, CD19, makes the T cells
attack B lymphocytes -- the cells that
become cancerous in CLL.

All this has been done before. These
genetically engineered cells are called
chimeric antigen receptor (CAR) T
cells. They kill cancer in the test tube.
But in humans, they die away before
they do much damage to tumors.

What's new about the current
treatment is the addition of a special
signaling molecule called 4-1BB. This
signal does several things: it gives
CAR T cells more potent anti-tumor
activity, and it somehow allows the
cells to persist and multiply in patients'
bodies. Moreover, the signal does not
call down the deadly all-out immune
attack -- the feared "cytokine storm" --
that can do more harm than good.