* Oral JAK inhibitor meets primary goals at several doses
* Tops placebo in ACR20 rate and remission rate
* In combo with methotrexate, tops methotrexate alone
By Bill Berkrot
NEW YORK, Oct 17 (Reuters) - An experimental rheumatoid arthritis drug being developed by Pfizer Inc (PFE.N) was effective as a stand-alone and in combination with a standard treatment for the disease, according to final analysis of data from a pair of mid-stage studies.
The drug, CP-690,550, belongs to a new class of medicines known as oral JAK inhibitors being tested for their impact on enzymes that affect signaling of proteins involved in inflammatory and autoimmune diseases.
Researchers tested several doses of the Pfizer drug in 24-week, Phase II studies, with some proving highly effective in providing relief from rheumatoid arthritis symptoms and near remission of disease activity, researchers said.
“I think this is going to be a very significant, dramatic addition to the armamentarium,” Dr. Roy Fleischmann, clinical professor of medicine at University of Texas Southwest Medical Center in Dallas and lead investigator in the monotherapy study, said in an interview.
The JAK inhibitor is considered to be one of the most promising drugs in Pfizer’s developmental pipeline.
“People should be extremely excited about it. It’s an oral drug, not injectable, so it’s easy to take, and it should be cheaper than the biologics,” said Fleischmann, who will present data next week at an American College of Rheumatology scientific meeting in Philadelphia.
In the monotherapy study of 384 patients with active rheumatoid arthritis who had not responded to other anti-rheumatic drugs, those who received the 5 milligram, 10 mg or 15 mg doses of the Pfizer drug twice daily had significantly better response rates at 24 weeks than those who received a placebo. The 1 mg and 3 mg doses did not achieve statistical significance compared with the placebo.
In addition, patients taking the three higher doses had statistically significant DAS 28 remission rates, meaning the disease was no longer active or reduced to near remission.
The primary goal was the ACR20 response rate, or at least a 20 percent reduction in disease activity and symptoms, such as tender and swollen joints and inflammation.
At 15 mg, 66.7 percent of patients achieved ACR20, while 65.6 percent hit the mark at 10 mg and 51 percent on the 5 mg dose. That compared with 25.4 percent who received a placebo.
The DAS28 remission rate was 21.1 percent at 15 mg, 21.3 percent at 10 mg, 14.6 percent at 5 mg and 13.7 percent at 3mg — all statistically significant compared with a mere 1.8 percent remission rate in the placebo group.
“The monotherapy study clearly shows that CP-690,550 is effective certainly versus a placebo, and in the combination study, it’s effective as well,” said Fleischmann. “It appears that no matter how you use it, it’s effective,” he added.
The second 24-week study involving 507 patients with active rheumatoid arthritis tested the same five doses of CP-690,550 twice daily and a 20 mg dose once daily in combination with the commonly used rheumatoid arthritis treatment methotrexate versus methotrexate alone.
Patients in the 3 mg, 10 mg, 15 mg and 20 mg plus groups all had statistically significantly higher ACR20 rates than those on methotrexate alone. The 15 mg patients had the highest ACR20 rate at 58.7 percent compared with 34.8 percent in the methotrexate alone group.
The 5 mg group missed statistical significance with 47.9 percent achieving ACR20, though Fleischmann said it was a very near miss.
Pfizer has moved the 5 mg and 10 mg doses into larger Phase III studies it hopes will confirm the Phase II results.
While the 15 mg dose was highly effective, there were more serious adverse events with the higher dose, Fleischmann said.
The Pfizer drug does tend to raise the levels of bad LDL cholesterol, but Fleischmann said that is easily managed with statin drugs, such as Pfizer’s Lipitor.
Fleischmann said he hopes Pfizer will conduct direct comparison trials between the JAK inhibitor and a widely used biotech medicine, such as Humira.
“If it’s equivalent it’s a home run, if it’s better it’s a grand slam,” he said. (Reporting by Bill Berkrot; Editing by Steve Orlofsky)