Washington Editor

ADELPHI, Md. – An FDA panel in a 13-to-2 vote Tuesday recommended approval for Human Genome Sciences Inc.'s Benlysta (belimumab) as a treatment for adults with systemic lupus erythematosus (SLE), a chronic debilitating autoimmune disease that primarily affects women of childbearing age, although men, children and teenagers have been known to develop the condition.

Trading of HGSI's shares (NASDAQ:HGSI) was suspended Tuesday pending the panel's votes.

"This is a great milestone and a great day for patients," HGSI CEO Tom Watkins told reporters after the meeting.

"This is a historical moment," added Carl Russo, senior vice president of biopharmaceutical development at GlaxoSmithKline plc – HGSI's development and commercialization partner.

Indeed, if the FDA follows its panel's advice, Benlysta, a recombinant, fully human, IgG1λ monoclonal antibody, would be the first new lupus treatment in more than 50 years to enter the U.S. market and the only medicine specifically developed to treat the disease, which can cause arthritis-like symptoms, cardiovascular problems, anemia and other blood disorders, malar rash and irreversible organ damage, often leading to death.

The last time the FDA approved a lupus treatment, "Ike was president," and "Elvis topped the music charts," Sandra Raymond, CEO of the Lupus Foundation of America, told the FDA's Arthritis Advisory Committee Tuesday as one of more than 30 public speakers who urged the agency, in what was often passionate pleas, to approve Benlysta.

There currently are only three drugs approved in the U.S. for SLE: aspirin, corticosteroids and Plaquenil (hydroxychloroquine), an antimalarial. Although, immuno-
suppressives are used off label to treat the disease, noted Rosemarie Neuner, a clinical reviewer in the FDA's Division of Pulmonary, Allergy and Rheumatology Products.

But current lupus treatments have broad negative effects on the immune and inflammatory systems and are associated with toxicity and poor tolerability, limiting most patients' ability to achieve sufficient management of their disease, said Diana Daly, executive director of regulatory affairs at HGSI.

The committee voted 10 to 5 that HGSI's two Phase III trials of Benlysta 10 mg/kg – which met their primary endpoints – demonstrated substantial evidence of efficacy for reducing disease activity in patients with active, auto-antibody-positive SLE. Although, one panelist, Dennis Dixon, a biostatistician at the National Institute of Allergy and Infectious Diseases, said he would have been inclined to vote yes had he not stuck strictly to voting on the way the question was worded, without caveats about the drug's labeling. (See BioWorld Today, July 21, 2009, and Nov 3, 2009.)

Indeed, in backing the drug's efficacy, several panelists insisted that the FDA ensure Benlysta's labeling emphasize that the drug was not studied in patients with more severe forms of lupus, such as renal impairment and central nervous system (CNS) lupus. Some panelists also raised concerns about the lack of Benlysta's efficacy in African-American patients in HGSI's Phase III studies, which is a concern because patients of African-American or African heritage are known to have more aggressive SLE and develop renal disease more frequently, often leading to worse outcomes.

Only 14 percent of patients in HGSI's BLISS-76 (study 1056) were African American, and only about 4 percent of patients in its BLISS-52 (study 1057), which was conducted outside the U.S., were from that population.

Compare that to the 25 percent of African-American lupus patients in the U.S. "and we are not really getting an accurate sampling," complained panelist David Blumenthal, a rheumatologist and professor of medicine at Case Western Reserve University in Cleveland.

He argued that HGSI's Phase III studies could not be extrapolated to the SLE population in the U.S., especially for the African-American population.

HGSI's Daly said her firm was committed to further studying Benlysta in black lupus patients.

The FDA's concerns about infection, malignancy, suicidality and death did little to persuade the panel against Benlysta's safety, with panelists voting 14 to 1 that the drug's safety profile was sufficient for approval.

While most of the committee said Benlysta's adverse effects could be managed with strong warnings in the labeling and prescriber education, many called for more studies to further investigate the long-term safety of the medicine and its potential adverse effects in certain populations.

Daly noted that HGSI and GSK have ongoing trials of Benlysta and have agreed to continue studying the drug once it has reached the U.S. market. Watkins declined to provide any further details about the ongoing studies or any trials the firm plans postmarketing, stating that it would be inappropriate to comment with Benlysta's application still under review.

The FDA is expected to make a decision about Benlysta by Dec. 9, the Prescription Drug User Fee Act action date.

HGSI's Watkins said that if Benlysta wins the FDA's OK, the drug could potentially be available to patients in early 2011.

Benlysta also has applications pending before regulators in Europe, Canada and Russia.