Johnson & Johnson’s experimental drug siltuximab improved symptoms and shrank growths in patients with Castleman disease, a rare condition marked by enlarged lymph nodes with no approved therapies, in a clinical trial.
The medicine, a monoclonal antibody, targets a molecule believed to fuel excess growth of lymphatic cells that is overproduced in patients. The study funded by New Brunswick, New Jersey-based J&J focused on people with numerous damaged lymph nodes that can lead to a dangerously weakened immune system.
One-third of patients on siltuximab responded to treatment, compared with none of those given a placebo, according to the results being discussed today at the American Society of Hematology meeting in New Orleans. The study is the first randomized trial of any drug for the disease, which is currently treated with chemotherapy to kill the dividing cells. Doctors also use Rituxan, from Roche Holding AG and Biogen Idec Inc., which destroys the immune system’s B cells.
“Doctors have often done things that weren’t based entirely on science because it’s such a difficult disease to study,” said Stephen Ansell, a hematologist at the Mayo Clinic in Rochester, Minnesota, who wasn’t involved with the trial. “This looks like a pretty promising therapy. Hopefully it’s a stepping stone that we can use to build on the things we have.”
The disease is so rare that Helgi van de Velde, senior director of oncology research at J&J’s Janssen unit, couldn’t offer a guess as to how many people may be affected. It took two years to find 79 patients from nearly two dozen countries to enroll in the trial. All the patients were given best supportive care, such as medicine to reduce fevers and fight infection. The trial didn’t include Rituxan or chemotherapy.
The company submitted its findings to regulators in the U.S. and Europe in September in hopes of an early approval. The medicine, which is also being studied for smoldering multiple myeloma, was granted orphan drug status for Castleman disease. Medicines for rare diseases can qualify for orphan drug status in the U.S. and Europe, a designation that gives pharmaceutical companies exclusive marketing rights as an incentive to develop products that may benefit only a small patient population.
The study is from the second of three phases needed to get U.S. regulatory approval. The researchers didn’t include anyone with an HIV infection or human herpesvirus-8, two viruses that have been associated with the disease. The treatment boosted levels of hemoglobin and reduced signs of damage in laboratory tests, such as lowering levels of inflammation and fibrinogen, a liver protein involved in blood clotting.
Twenty-five percent of siltuximab-treated patients had all symptoms of the disease completely resolved for a median duration of 1.3 years. The most frequent side effects were itching, rash and swelling, with similar rates of other complications. One person developed an allergic reaction after taking the drug.
“If siltuximab gains regulatory approval, this experimental therapy could become the first globally approved treatment for this incurable disease and could potentially transform how patients are treated in the future,” said Raymond S. Wong, the lead researcher from Prince of Wales Hospital and the Chinese University in Hong Kong.