Immunomedics Inc. is starting two pivotal trials to evaluate its humanized monoclonal antibody, epratuzumab, in patients with moderate and severe forms of systemic lupus erythematosus.

The placebo-controlled, double-blinded studies will enroll two groups of lupus patients across the U.S., Europe, South America and Canada. Called ALLEVIATE A (Alleviate Lupus Affliction with Epratuzumab and Validate its Autoimmune Safety and Efficacy), the first trial will evaluate patients who are "in flare," or have high disease activity, while ALLEVIATE B will test epratuzumab in patients with moderate disease activity.

"This is a major milestone for us," said Cynthia Sullivan, president and CEO of the Morris Plains, N.J.-based company, adding that "there has not been a new drug for these patients in about 40 years."

That medical need prompted Immunomedics to move forward in lupus, though the company also is ready to move forward in Phase III studies of epratuzumab in non-Hodgkin's lymphoma. The product was awarded fast-track status in lupus by the FDA, and with resources to support trials in only one indication, "we opted to go with lupus," Sullivan said.

The FDA recently issued a draft guideline for the development of lupus drugs, and Immunomedics has been working with the agency on a protocol for Phase III trials, which will evaluate disease activity in patients based on the BILAG (British Isles Lupus Assessment Group) index. The company said specific trial endpoints will be disclosed at a later date.

Lupus, which results in chronic inflammation and pain and affects an estimated 3 million to 5 million people worldwide, occurs primarily in women and often during child-bearing years, Sullivan said, leading to "a dilemma for many patients," wondering if they should put off starting families due to issues of toxicity caused by existing treatments. Drugs prescribed to lupus patients include corticosteroids and other immunosuppressants that suppress the entire immune system and increase the risk of "viral and bacterial infections and all other complications associated with suppressed immune systems."

Epratuzumab, developed using Immunomedics' humanized antibody technology, is designed to selectively suppress the immune system. The drug targets the antigen CD22 and appears to cause only a mild depletion of circulating B lymphocytes by modulating B-cell function.

"The ability to change how those B cells function is the basis for the therapeutic," Sullivan told BioWorld Today. Patients receiving epratuzumab in the Phase II study all "responded favorably to the drug, and they all were less tired, had less joint pain" and fewer skin rashes.

Patient accrual for the pivotal studies is expected to occur quickly, and Immunomedics anticipates data in two years. Sullivan said it is in discussions to out-license epratuzumab for final clinical development and commercialization.

In addition to non-Hodgkin's lymphoma, epratuzumab is being development as a treatment for other autoimmune diseases, including Sjogren's syndrome, a disorder involving the attack on salivary glands by white blood cells. Immunomedics has had a Phase I/II trial in that indication and is expected to release data next week.

A second humanized B-cell antibody, IMMU-106, developed similarly to epratuzumab, is in Phase I/II trials for non-Hodgkin's lymphoma in the U.S. and Europe. The company also is evaluating an antibody, known as yttrium-labeled PAM4, in pancreatic cancer and is enrolling patients in Phase I/II studies. Plans for future studies include the combination of PAM4 with gemcitabine in pancreatic cancer.

The company posted a net loss of $6.1 million, or 11 cents per share, for the first three months of 2005. Research and development costs for the quarter totaled nearly $5.8 million. As of March 31, Immunomedics had cash, cash equivalents and marketable securities of about $11.8 million.

Shares of Immunomedics (NASDAQ:IMMU) rose 12 cents Thursday to close at $2.05.