New Lupus Drug Showed Positive Results In Trial Said Manufacturer

A phase 2 trial of the drug belimumab in patients with active systemic lupus erythematosus (SLE) showed positive results, according to the drug company.

Human Genome Sciences (HGS) of Rockville, Maryland, USA, told delegates attending the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen on 11 June that the four-year trial results showed "sustained improvement in disease activity and patient response rate", frequency of disease flares went down, and there was no overall increase in adverse events, serious or otherwise.

HGS and GlaxoSmithKline (GSK) have agreed terms to develop and sell belimumab, formerly LymphoStat-B and now known under the brand name Benlysta. Under the agreement HGS will conduct the phase 3 trial, with help from GSK.

Lupus is an autoimmune disease that affects mainly women in their childbearing years. The immune system attacks the patient's own body and tissue, causing inflammation at the site of the attack, which varies from person to person.

Estimates suggest there are 5 million people worldwide living with various forms of lupus, including SLE, 1.5 million of them in the US. For many people with lupus it is little more than a nuisance, but for some it is life-threatening.

Symptoms of lupus vary, depending on which part of the body is affected, for instance it could be a rash if the skin is attacked, or joint pain if the joints are attacked. For this reason lupus often mimics other diseases such as multiple sclerosis and rheumatoid arthritis and can be very difficult to diagnose. There is no single definitive test of the disease and accurate diagnosis relies on a number of factors, including symptoms and history.

There are two types of lupus: discoid, which affects only the skin, and the other is systemic (full name systemic lupus erythematosus, SLE), which affects the skin, joints and often internal organs such as the heart and/or kidneys. Belimumab, the drug tested in this trial, is designed to treat the second type, SLE.

Dr Joan T Merrill, a study investigator, Program Chair, Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, and Professor, Department of Medicine, University of Oklahoma Health Sciences Center, said that the results presented at EULAR 2009 suggest:

"The apparent durability of clinical effect and the favorable safety profile observed for belimumab suggest that belimumab has the potential to become an important new treatment for patients with SLE."

HGS Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases, Dr William W Freimuth, said they were encouraged by the results and the safety data presented at the meeting.

"The incidence rates per 100 patient years of all adverse event categories, including serious adverse events, overall adverse events, and serious infections were similar for belimumab and placebo during the 52-week double-blind period, and remained the same or decreased over four years of continuous treatment," said Freimuth.

Depending on how well Benlysta (belimumab) performs in the phase 3 trial, the drug could "represent a significant advance in the treatment of SLE", he added.

The phase 3 data for Benlysta will appear in July 2009 from the BLISS-52 trial, and in November 2009 from the BLISS-76 trial. Both these trials are the largest clinical trials ever conducted in lupus patients, said HGS in a press statement.

Benlysta (belimumab) is a human monoclonal antibody that selectively targets and inhibits the B-lymphocyte stimulator (BLyS), a naturally occurring protein discovered by HGS. The protein plays an important role in turning B-lymphocyte cells into mature plasma B cells, which produce antibodies, the immune system's first line of defence against infection (the "foot soldiers" of the immune system).

Higher than normal levels of BLyS produce too many antibodies, which appears to correlate with the severity of disease in lupus and other autoimmune illnesses.

"Preclinical and clinical studies demonstrate that BLyS antagonists can reduce autoantibody levels and help control autoimmune disease activity," said the HGS statement, which stated that the trial data presented at the EULAR 2009 meeting showed:

- Continued treatment with Benlysta (belimumab) was associated with "sustained improvement or stabilization of SLE disease activity and with decreased frequency of SLE disease flares in serologically active patients through four years of treatment".

- The overall incidence of adverse events, serious or otherwise, infections and malignancies, including lab abnormalities either decreased or stabilized from week 52 to week 208 of the trial.

- Increase from 46 to 57 per cent in the response rate that was chosen as the primary endpoint of the phase 3 trial. This was a cluster of measures, including:" improvement in SELENA SLEDAI score of 4 points or more, no BILAG worsening, and no worsening in Physician's Global Assessment; post hoc; intention-to-treat analysis".

- Decrease from 62 to 16 per cent in the overall frequency of SLE flares, as measured by the SELENA SLEDAI Flare Index.

- Plus a decrease from 8 to 1 per cent in frequency of severe flares.

- Decrease from 23 to 5 per cent in frequency of patients having one new BILAG A organ domain score, or more than one new BILAG B organ domain score (BILAG A indicates a severe flare, while B indicates a moderate flare due to lupus disease).

For the trial, which evaluated the effectiveness and safety of Benlysta (belimumab) plus standard care against placebo plus standard care, a total of 449 SLE patients were randomly assigned to have either one of three different doses of the active drug or placebo over 52 weeks.

At the end of 52 weeks, 345 of the patients chose to continue in an optional 24 week extension, during which all patients received the active drug. At the end of 76 weeks, 296 patients chose to continue with belimumab in an "open-label long-term continuation phase" where all patients were given the same dose. The current situation, as of 1 June 2009, is that 213 patients are still receiving treatment in the continuation study, said HGS.

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