A closely watched experimental drug for rheumatoid arthritis being developed by Pfizer 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 significance.
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 medicines.
"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 scale.
"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, which is expected to have sales in excess of $6 billion this year, or Amgen Inc's 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 patients.
"It has a safety profile that is very reasonable because the benefit is so good and the risk relatively small," Fleischmann said.
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