Repligen Corp.'s stock spiked 25 percent Thursday on Phase III findings that showed that a monoclonal antibody to which it has unresolved intellectual property claims, CTLA4-Ig, might represent a new treatment option for patients with rheumatoid arthritis.
The company owns U.S. and European patent rights to the product's use in RA, but Bristol-Myers Squibb Co. also has rights as a result of rulings in past litigation. The data, which stem from two Phase III trials sponsored by BMS, suggest that the drug might benefit patients who do not adequately respond to current treatments such as methotrexate and inhibitors of tumor necrosis factor (TNF).
For Waltham, Mass.-based Repligen and BMS, the findings point to CTLA4-Ig's promise. But once the drug moves closer to commercialization, intellectual property matters again could arise.
"There's not a relationship between Repligen and BMS at this point," Laura Whitehouse, Repligen's vice president of market development, told BioWorld Today. "But our position would be at some point we're going to have to talk about this patent we have. Our U.S. patent was issued in February, and BMS does note the patent in its 10Q filings."
Courtesy of exclusive license agreements with the University of Michigan and the U.S. Navy, Repligen specifically owns a U.S. patent that covers a method of treating rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis and scleroderma with CTLA4-Ig and the use of CTLA4-Ig in combination with other immunosuppressants. Repligen also has a corresponding patent in Europe.
The U.S. patent will remain in force until 2021, while its European counterpart will remain in force until 2013. The U.S. patent was issued after a U.S. District Court ruled in favor of BMS in a complaint filed by Repligen and the University of Michigan related to the inventorship of CTLA4 patents. CTLA4-Ig is the soluble form of CTLA4, which is believed to have immunosuppressive activity. (See BioWorld Today, Sept. 18, 2003.)
Repligen has advanced the protein into Phase I studies for multiple sclerosis, but would be blocked by BMS' patents to take CTLA4-Ig to the market for that indication.
"If we were to bring our form of the molecule forward, we would need a license from BMS," Whitehouse said. "It's really more of an intellectual property situation than clinical for us, per se, because we would need to have cross-licensing."
She said both parties have had open communication lines in the past, sometimes centered on the prior patent dispute, and added that Repligen would be open to discussions going forward.
Outside of any potential patent discourse, Whitehouse pointed to the positive results reported by BMS at the American College of Rheumatology meeting in San Antonio.
The first study compared 10 mg/kg of the drug plus methotrexate to methotrexate alone, and after six months of treatment, 67.9 percent of combination patients achieved an ACR 20 response, compared to 39.7 percent receiving placebo plus methotrexate (p<0.001). The second study also evaluated a 10 mg/kg dose, this time in patients with active rheumatoid arthritis who were not adequately responding to at least three months of treatment with TNF inhibitors. After six months, 50.4 percent of CTLA4-Ig patients achieved an ACR 20 response compared to 19.5 percent for the placebo group (p<0.001).
"The news is fabulous from a clinical standpoint," Whitehouse said, noting that at least 25 percent of patients are refractory to TNF-inhibitor treatment. "The BMS study that looks specifically at those patients that didn't respond to TNF inhibitors and showed clinical benefit in that patient population is very exciting news, because that's a patient population that doesn't have any other options."
In both studies, CTLA4-Ig was generally safe and well tolerated with a low incidence of infusion reactions and serious infections.
Repligen said New York-based BMS plans to file a new drug application for its form of CTLA4-Ig by the end of the year.
Beyond CTLA4-Ig, Repligen's portfolio primarily is focused on central nervous system drugs. Secretin is in Phase II for schizophrenia and Phase I/II for obsessive compulsive disorder, while Uridine is expected to enter Phase II in the first half of next year for bipolar disorder. Earlier in development is therapeutic protein A, which is expected to move into the clinic in the second half of next year for cancer and autoimmune disorders.
On Thursday, Repligen's stock (NASDAQ:RGEN) gained 48 cents to close at $2.40.