Pfizer arthritis drug succeeds in late stage trial

* Meets goal on two of three primary endpoints -study

* Significantly improves symptoms, physical function

* Serious adverse events seen in 4.1 pct of patients

By Bill Berkrot

NEW YORK, Nov 7 Reuters) – A closely watched experimental
drug for rheumatoid arthritis being developed by Pfizer Inc
(PFE.N: ) significantly reduced symptoms and improved physical
function, according to data from a late-stage clinical trial.

The drug, tasocitinib, met two of three primary goals of
the 611-patient Phase III study at two tested doses, compared
with a placebo, the data show.

On the third primary goal, tasocitinib demonstrated a
numerically higher measure of disease remission at three months
than placebo, but that measure did not reach statistical

Tasocitinib belongs to a new class of oral drugs, known as
JAK inhibitors, that impacts the signaling of proteins involved
in inflammatory and autoimmune diseases. It is a hot area of
research with several other drugmakers pursuing similar

“This is the first oral medication for rheumatoid arthritis
that has had a successful Phase III study this century,” Dr Roy
Fleischmann, the study’s primary investigator, said in a
telephone interview.

“When it works, it really works,” said Fleischmann, who
will present the results at the American College of
Rheumatology meeting in Atlanta this week.

Tasocitinib is considered one of the most promising drugs
in Pfizer’s developmental pipeline. It has garnered
multibillion-dollar peak sales projections from analysts, which
is not uncommon for a successful rheumatoid arthritis drug.

On the study’s first primary goal, 65.7 percent of patients
who received 10 milligrams of tasocitinib twice a day achieved
ACR20, meaning at least a 20 percent improvement in disease
activity and symptoms, after three months of treatment. Nearly
60 percent of 5 mg patients reached ACR20, compared with 26.7
percent of those who received a placebo, researchers said.

The study also measured much tougher to hit ACR70 rates, or
at least a 70 percent improvement. At 10 mg 20.3 percent of
patients achieved ACR70, while 15.4 percent hit that mark with
the 5 mg dose. That compared with 5.8 percent on placebo.

The second primary goal was a patient-reported gauge of
improvement in physical functions, such as ability to fasten
buttons. On that measure, the Pfizer drug more than doubled
what would be considered to be a minimal clinically important
improvement, Fleischmann said.

On a 0-to-3 scale in which 0 to 0.5 is considered normal
function, patients began the trial with an average score of
1.5, which represents moderate-to-severe function limitation.

Placebo led to a drop of just 0.19. Patients who received
10 mg of the JAK inhibitor experienced a drop of 0.57, while
patients taking 5 mg improved by 0.5, or half a point on the

“That’s a major difference that’s very meaningful to a
patient. A patient can really tell the difference,” Fleischmann
said of the response to tasocitinib.

Rheumatoid arthritis is a painful, chronic autoimmune
disorder in which the body’s immune system attacks healthy
tissue, causing inflammation in and around the joints. The
condition affects 1.3 million people in the United States and
about 1 percent of adults worldwide, Pfizer said.

It is commonly treated with injected biotech drugs, such as
Humira from Abbott Laboratories (ABT.N: ), which is expected to
have sales in excess of $6 billion this year, or Amgen
Inc’s(AMGN.O: ) Enbrel, which is on track for 2010 sales of more
than $3.5 billion.

Fleischmann said patients being helped by the biologics are
always asking for a version in pill form, making the JAK
inhibitor a very attractive option.

“It’s an oral pill taken every day, rather than an
injection. It seems to work similar to biologics and it’s
certainly more convenient for patients,” he said.

All patients in the Pfizer-sponsored study had active
moderate-to-severe rheumatoid arthritis following an inadequate
response to prior treatment with at least one other drug.

Serious adverse events were reported in 25 tasocitinib
patients, or 4.1 percent, with six cases of serious infection
reported over the six months of the study.

“What we have not seen so far is the tuberculosis, or the
opportunistic infections that we’ve seen with the biologics,”
Fleischmann said.

Less serious adverse events were reported in more than half
of tasocitinib patients over the first three months of the
trial. They included decreases in white blood cells and
increases in bad LDL cholesterol, compared with placebo. There
was also an increase seen in good HDL cholesterol as well as an
increase in red blood cell count and in liver enzymes in some

“It has a safety profile that is very reasonable because
the benefit is so good and the risk relatively small,”
Fleischmann said.
(Reporting by Bill Berkrot; editing by Gunna Dickson and Diane

Pfizer arthritis drug succeeds in late stage trial