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

By Catherine Arnst

Editor's Note: The report mentioned in the fifth paragraph came from Lazard Capital Markets, not Lazard Freres, as previously reported.

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 Capital Markets 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.

Arnst is a senior writer for BusinessWeek based in New York.

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