Washington Editor

While Human Genome Sciences Inc.'s positive Phase III BLISS-76 results of Benlysta (belimumab) in patients with systemic lupus erythematosus (SLE) were not as robust as those released in July from its Phase III BLISS-52 trial, investors nonetheless were pleased, and took the Rockville, Md.-based firm's stock for another ride, with shares jumping 35.3 percent Monday.

The biotech's shares (NASDAQ:HGSI) gained as much as $7.52 before closing at $25.28 Monday, an increase of $6.59.

HGS' shares took a 277-percent rocket ride on July 20 after the company announced Benlysta had met its primary endpoint in BLISS-52. (See BioWorld Today, July 21, 2009.)

With the second Phase III primary endpoint met for the key 10 mg/kg dose, FDA approval of Benlysta, which is being co-developed with London-based GlaxoSmithKline plc, is more assured, analysts said.

J.P. Morgan analyst Cory Kasimov gave a "Phew!" of relief over the BLISS-76 top-line results, which he called Benlysta's "defining test."

However, he noted that the 52-week treatment effect results for Benlysta in BLISS-76 were lower than seen in BLISS-52, 9.4 percent vs. 14 percent, respectively.

The 1 mg/kg dose in BLISS-76 failed to achieve statistical significance, which it had achieved in BLISS-52. But, Kasimov pointed out, that dose was not critical for the latest trial's success or approval of the drug.

The bottom line, said Leerink Swann analyst Joseph Schwartz, is that the BLISS-76 results have provided increased confidence in Benlysta's approvability.

Benlysta, the first in a new class of drugs called BLyS-specific inhibitors, is the first new lupus drug to achieve positive results in an advanced-stage study, said H. Thomas Watkins.

No new drugs have been approved in more than 50 years for SLE, the most common form of lupus, a chronic and potentially fatal autoimmune disease, he noted.

The Lupus Foundation of America has estimated that up to 2 million Americans have a form of lupus, a disease that predominantly affects women.

About 325,000 people in the U.S. have SLE, Watkins added.

"And to have not one but two positive Phase III trials gives them real hope," he told BioWorld Today.

While BLISS-76 is a 76-week study, the data were analyzed after 52 weeks, because the primary efficacy endpoint of both BLISS-52 and BLISS-76 is the patient response rate at week 52, David Stump, executive vice president of R&D at HGS, told investors and analysts during a conference call Monday.

The studies comprise the largest clinical trial program ever conducted in lupus.

The primary efficacy endpoint for both trials was the patient response rate at week 52 of a clinically important reduction in SLE disease activity, no worsening of disease and no new severe or moderate flares of lupus disease activity.

In each of the Phase III trials, patients were randomized to receive either 10 mg/kg or 1 mg/kg of Benlysta or placebo, plus the standard-of-care treatment. Based on an intent-to-treat analysis, Benlysta 10 mg/kg met its primary efficacy endpoint of superiority over placebo at week 52 in improvement, 43.2 percent vs. 33.8 percent, which was statistically significant. However, the 1 mg/kg response was 40.6 percent, which was not statistically significant.

Benlysta was generally well tolerated in the BLISS-76 study, with rates of overall adverse events, including serious or severe events, comparable with the placebo treatment group, Stump said.

Overall infections, including those that were serious or severe, were also comparable to placebo, he added.

About 2,200 patients to date have received Benlysta in clinical trials, Watkins said.

By the time the company files its biologics license application with the FDA, which is expected to be completed by the end of the first half of next year, the firm anticipates having about six years of safety data on the drug, he said.

HGS will take the lead in filing the application in the U.S, with GSK filing in Europe and other countries outside the U.S., Watkins said.

But, he insisted, "It is very much a joint effort."

HGS plans to seek priority review, which if achieved, means Benlysta could be on the market by the end of next year, Watkins said.

"That would be real exciting for us," he said.

Assuming Benlysta is approved by regulatory agencies in the U.S., Europe and elsewhere, "we believe that it could represent a breakthrough in the treatment of patients suffering from SLE," Stump said.

With the second Phase III trial meeting its primary endpoint, said Barry Labinger, chief commercial officer at HGS, "It is now more obvious than ever that Benlysta has the potential to be a drug for a major unmet need with clear evidence supporting its efficacy and safety."

The commercial potential for Benlysta is "very exciting" based on a large patient population and "clearly inadequate treatment options."

Plaquenil hydroxychloroquine and low-dose steroids are generally used as first-line therapies for SLE. While those agents can be helpful for awhile, most patients require more intensive therapy at some point in the course of their disease, Labinger noted.

"Right now, the only real alternatives are to increase the dose of the steroids or adding an immunosuppressant, both of which come with significant safety concerns over the long run," he insisted.

In fact, Labinger said, "many patients describe the side effects of these drugs as just as bad as the disease itself."

Benlysta, he argued, "has the potential to become the alternative that, unlike any other available treatment, offers proven efficacy in providing durable control of lupus activity and a favorable safety profile."

Benlysta has demonstrated the potential to redefine the standard of care in the treatment of lupus, Watkins said.

"Anytime a new drug can offer that kind of value to patients, a significant commercial opportunity comes along with it," Labinger contended.