Benlysta Effective in Some Lupus Sufferers
GlaxoSmithKline and Human Genome Sciences limited the drug's Phase 3 trial to patients testing positive for the protein that Benlysta blocks, greatly boosting trial results.
The experimental lupus drug Benlysta has defied skeptics by significantly improving the symptoms of this difficult-to-treat disease in a late stage trial, announced Human Genome Sciences (HGSI) and partner GlaxoSmithKline (GSK) on Monday.
Benlysta failed a mid-stage Phase 2 trial completed in 2006, leading many market analysts to consign the drug to a growing scrap heap of unsuccessful treatments against lupus. But in reexamining the data from the failed trial, HGS found that Benlysta did appear effective in a subset of patients, about 75%, with certain immune-system proteins circulating in their blood. Using that information, the company changed the design of the Phase 3 trial, including only those patients in whom the drug was likely to work. After 52 weeks, the company reported that the drug met the primary goal of the trial—a statistically significant improvement in patient symptoms when compared with the placebo—and reduced the number of patients who needed steroids to control their symptoms. The drug was also well-tolerated, with no difference in side effects between the patients taking Benlysta and those on the placebo. Investors reacted to the trial results by sending HGS's price soaring in pre-market trading on Monday, tripling it to $10.88 a share from Friday's close of $3.32.
Lupus is a chronic and often life-threatening disease in which the immune system goes out of control and attacks connective tissue in the joints, lungs, kidneys, and heart. It afflicts some 5 million people worldwide, including 1.5 million in the U.S. The disease typically strikes between the ages of 15 and 45 and is most common in women and African Americans. Common symptoms can include extreme fatigue, swollen joints, fever, rash, and kidney problems, though they vary significantly from person to person.
No new drugs to treat lupus have introduced in the past 30 years. Scientists have yet to determine what causes the disease, and there was little understanding of it until the 1990s. In the past year a promising candidate from La Jolla Pharmaceutical (LJPC) and BioMarin Pharmaceuticals (BMRN) failed its clinical trial, as did Roche and Biogen Idec's (BIB) Rituxan, a drug already approved for other immune diseases.
in failure, the seeds of success
Those past failures, combined with Benlysta's unsuccessful Phase 2 trial, led several analysts to issue skeptical reports about HGS and its drug last week. The common refrain, as echoed in a Lazard Freres report: "We continue to believe the probability that [Benlysta] succeeds is extremely low." As a result, HGS's stock price gyrated up and down last week, rising from $2.50 per share on Monday to as high as $3.98 on Thursday before closing Friday at $3.32. "I think the skepticism is certainly understandable given how many studies have been done in lupus that have not succeeded," said HGS President H. Thomas Watkins.
But in this case, failure appears to have contained the seeds of a limited success. HGS officials said they learned from the Phase 2 trial which patients were most likely to respond to the drug—specifically, those who test positive for the immune system protein that the drug blocks. This type of after-the-fact, or subgroup, analysis of clinical-trial results is frowned on by many scientists and the FDA, but the company felt the analysis allowed it to design a Phase 3 trial with a better chance of success, thus saving a drug that could be effective against a disease that can cause immense suffering.
In June, HGS and Glaxo reported that a four-year followup of patients in the Phase 2 trial that met the subgroup criteria found that the drug decreased both the severity and frequency of symptoms. The company will report the full results of the Phase 3 trial at an upcoming medical meeting, Watkins said. Until analysts and specialists comb over that data, it's likely that a lot of skeptics will remain.
HGS and Glaxo also have to complete a second Phase 3 trial for Benlysta, in which they are following 826 patients for 76 weeks. Those results are expected in November. Watkins says if the second trial is also positive, the company will file with the FDA for approval in the first half of 2010.
Lupus Research Institute Highly Encouraged by Benlysta™ Trial Results
First Phase 3 Lupus Drug Trial in Decades to Show Effectiveness
The Lupus Research Institute (LRI) and its National Coalition of state and local organizations of which the Lupus Alliance of America LIQ Affiliate belongs to, congratulate Human Genome Sciences (HGS) and GlaxoSmithKline on the highly promising results of this landmark clinical trial of Benlysta™ (belimumab) for people with systemic lupus.
“We are very hopeful that we now are strongly on our way to the first new treatment for lupus in 50 years,” said LRI President, Margaret G. Dowd. “We look forward to the impact that a new drug for lupus will have on the lives of the 1.5 million Americans, and millions more worldwide, who suffer from this devastating autoimmune illness.”
“This is a major advance for patients, families, and physicians—the entire lupus community!” said Richard Furie, MD, chief of the division of rheumatology and allergy-clinical rheumatology at North Shore-LIJ Health System in New York. “There is no doubt that a drug approval will foster further drug development and additional discoveries.”
In the double-blind, placebo-controlled, multi-center trial, known as BLISS-52, both dose levels of Benlysta™ plus standard of care were more effective than a placebo plus standard of care in people with serologically active systemic lupus. A total of 867 participants at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe, were enrolled in the trial.
“This is the first drug shown to be effective in ameliorating the signs and symptoms of lupus in decades,” said Daniel J. Wallace, MD, clinical professor of medicine at the David Geffen School of Medicine at UCLA. “It represents a breakthrough for finally utilizing a methodology that enables researchers to demonstrate disease improvement. This will benefit lupus patients and their doctors.”
Results of a second Phase 3 trial of Benlysta™, known as BLISS-76, are expected later this year. That trial has enrolled 826 participants at 133 clinical sites in 19 countries, primarily in North America and Europe.
BLISS-52 and BLISS-76 are the largest clinical trials ever conducted in people with lupus.
First of its kind
“Benlysta™ is the first ‘targeted biological agent’ developed specifically for systemic lupus that has the potential to obtain FDA approval…with the positive results of this 52-week trial and pending the results of the 76-week trial,” said Tammy O. Utset, MD, MPH, an associate professor of medicine at the University of Chicago.
“HGS took a very ambitious development approach—huge international concurrent trials which represent a large investment in systemic lupus therapy," Utset added.
“The lupus community commends HGS and GlaxoSmithKline for their commitment and perseverance in finally bringing this potential new lupus treatment to trial,” said Dowd. “And we thank the hundreds of people with lupus who enrolled and took part in this important trial. Participation like theirs is critical to finding answers to this illness.”
The LRI builds the research pipeline and assists in recruiting patients to participate in trials to bring safe and effective treatments to market for people with lupus.
Published 07/15/09
Sources: HGS, Lupus Research Institute, Reuters