A month after announcing impressive early data with its hepatitis C drug, Vertex Pharmaceuticals Inc. had more good news to report when its rheumatoid arthritis drug, VX-702, met its primary endpoint in a Phase II trial.
The VeRA study enrolled a total of 315 patients randomized to receive either 5 mg or 10 mg of VX-702, a p38 MAP kinase inhibitor administered once daily, or placebo over a 12-week period. Patients in the trial were allowed to take certain disease-modifying drugs in addition to study treatment, but could not receive methotrexate or anti-TNF therapies.
Preliminary results showed a dose-dependent response rate, with 40 percent of patients in the 10-mg group and 38 percent in the 5-mg group demonstrating an ACR20 response vs. 30 percent of patients receiving placebo. The ACR20 assessment represents a 20 percent reduction in the number of tender or swollen joints, and a 20 percent improvement in certain physician and patient assessments.
"Overall, I think it’s a very strong data set," said Lynne Brum, vice president of strategic communications for the Cambridge, Mass.-based company. Data cover "a whole host of measures on the tolerability side, and additional measures of clinical activity, including EULAR [European League against Rheumatism] score. We also reported clinically significant changes in morning stiffness, and in swollen and tender joints.
"So, all in all, the results met our expectations," she added "We’re now able to move forward with development and test [VX-702] on a background of methotrexate in an additional three-month study expected to start in mid-2006."
Though the data were positive, some analysts said results weren’t positive enough. Vertex’s stock (NASDAQ:VRTX) lost $2.30 Thursday, to close at $37.98.
The biggest concern was that data fell short of expectations when compared with other treatments for rheumatoid arthritis. Biologics Humira (adalimumab) and Remicade (infliximab) demonstrated greater statistical significance in clinical testing, with Humira showing an ACR20 of more than 45 percent vs. 20 percent for placebo, and Remicade demonstrating a 52 percent ACR20 compared to 20 percent for placebo. (See BioWorld Today, Nov. 10, 1998.)
Both Humira, sold by Abbott Park, Ill.-based Abbott Laboratories, and Remicade, marketed by Malvern, Pa.-based Centocor Inc., are anti-TNF therapies.
On the plus side, however, VX-702 consistently has demonstrated safety in patients and healthy volunteers. No clinically significant effects were seen on laboratory parameters, and patients discontinuing treatment due to adverse events were 2 percent in the placebo arm, 3 percent in the 5-mg group and 5 percent in the 10-mg group. The most common adverse events were skin disorders, affecting 9 percent of the treatment group and none in the placebo group. Other side effects included infection (10 percent VX-702 vs. 5 percent placebo), and gastrointestinal disorders (8 percent VX-720 vs. 6 percent placebo).
Other companies developing anti-cytokine inhibitors like VX-702 have encountered safety issues in the past, so "we’re very happy with the tolerability profile that we saw," Brum said.
Analyst Andrew McDonald, of San Francisco-based ThinkEquity Partners LLC, called the safety data "a welcome surprise," and maintained his "buy" rating on Vertex. He wrote in a research note that he remains "cautiously optimistic" on the future development of VX-702, and described the Phase II study as an "important hurdle," though "much greater hurdles await."
Among those hurdles is the upcoming study of VX-702 in combination with methotrexate. That trial is expected to involve more than 200 patients, with doses to be determined following final analysis of the VeRA study. Depending on results, Vertex could move into a larger pivotal trial.
Because VX-720 is a once-daily, orally administered drug, Vertex believes it could find a place in the market, despite the existing anti-TNF therapies, such as Humira, Remicade and Thousand Oaks, Calif.-based Amgen Inc.’s Enbrel, which are all injectable.
"Our estimates put the worldwide sales of those [anti-TNF] drugs in 2005 at about $8 billion," Brum said. "So it’s a significant market opportunity."
Vertex holds development and commercial rights in the U.S. and Europe to VX-702, while Kissei Pharmaceutical Co. Ltd., of Tokyo, has rights to develop and market the drug in Japan and certain other Asian countries.
In addition to VX-702, Vertex has a number of other drugs in its pipeline targeting viral disease, inflammation, autoimmune diseases and cancer. Most recently, the company reported positive Phase II results with VX-950, a small-molecule protease inhibitor for treating hepatitis C. In that trial, VX-950 demonstrated an ability to reduce viral loads to undetectable levels in patients receiving the drug for about a month. (See BioWorld Today, Feb. 8, 2006.)