Washington Editor

For the second time in a couple of weeks, Biogen Idec Inc. has begun a pivotal cancer trial, this time with lumiliximab for chronic lymphocytic leukemia (CLL).

The randomized, controlled study will compare the primatized anti-CD23 monoclonal antibody in combination with the chemotherapies fludaribine and cyclophosphamide plus the antibody Rituxan (rituximab), an emerging standard of care known as FCR, to FCR alone in patients with CLL that have relapsed or failed to respond to initial therapy. CD23 is highly expressed in that disease, the second most common blood cancer in adults, and previous preclinical and clinical data show that lumiliximab induces apoptosis when binding to the target.

"The tolerability of lumiliximab with FCR appears to be the same as FCR alone," explained Arturo Molina, the company's senior director of its oncology research and development group, noting that the investigational drug has not added any toxicity to the existing combination regimen in previous testing.

"So our hypothesis is that we can increase the complete response rate by adding lumiliximab to FCR without increasing toxicity, and that the increased complete response rate will translate into a prolongation of progression-free survival," Molina said.

About 276 patients will be enrolled at more than 90 sites around the world in the study, which will measure the complete response rate differences between the two arms as its primary endpoint.

That design is based in part on Phase I/II data, reported at December's American Society of Hematology meeting, in which lumiliximab plus the FCR regimen demonstrated a 52 percent complete response rate in patients with CLL that was progressing after prior therapy, about double the historical FCR complete response rate of 25 percent.

Molina told BioWorld Today that the new trial should complete enrollment in 18 months or less, with data expected about six months later. Biogen Idec, of Cambridge, Mass., is calling the study the LUCID trial, an acronym for the evaluation of lumiliximab in combination with FCR in patients with relapsed CLL. A novelty in the study's design, Molina said, is stacking two targeted treatments, lumiliximab and Rituxan, with the two chemotherapies, which has produced an "enhancement of anti-leukemic efficacy" in lab studies.

Of note, the FDA has named lumiliximab an orphan drug and designated it a fast-track product. That means that this trial would support its registration in the U.S., assuming data are sufficient, and it could support European approval, too, though a confirmatory trial likely would be necessary there.

It's estimated that 77,000 Americans are living with CLL, and nearly a third of them are actively receiving treatment. Most of those patients are being treated in the relapsed setting, and about 10,000 new cases are expected to occur in the U.S. this year. In Europe, the numbers are similar.

Down the road, Biogen Idec plans to test lumiliximab with Rituxan, an anti-CD20 agent, in both front-line and maintenance settings for CLL. In addition, it's thought that lumiliximab could be used for small lymphocytic lymphoma, which also expresses CD23.

Should lumiliximab receive approval for CLL patients, it would join Rituxan and Campath (alemtuzumab), which targets CD52, as antibodies used for CLL. Chemotherapy and allogeneic stem cell transplants are additional treatment options, though Molina said the latter aren't optimal given that they're "fraught with" complications and toxicities in a patient population with a median age older than 60.

Biogen Idec owns lumiliximab's worldwide rights. The company's other newly initiated pivotal trial is testing galiximab, an anti-CD80 monoclonal antibody, in follicular non-Hodgkin's lymphoma.

On Wednesday, Biogen Idec's stock (NASDAQ:BIIB) gained 38 cents to close at $49.32.