Staff Writer

Detailed data from the first Phase III trial of Human Genome Sciences Inc.'s lupus drug Benlysta (belimumab) lived up to expectations, boosting analyst confidence in the outcome of a second Phase III trial to be revealed Nov. 2.

HGSI announced three months ago that its first Phase III trial had met its primary endpoint, with a 57.6 percent (p = 0.0006) response rate at the 10 mg/kg dose and a 51.4 percent (p = 0.013) response rate at the 1 mg/kg dose compared to 43.6 percent for placebo. The top-line data sent HGSI's shares rocketing up 277 percent. (See BioWorld Today, July 21, 2009.)

Analysts expected the detailed data, which were presented Tuesday in a late-breaker session at the American College of Rheumatology's annual scientific meeting, to be good - and they weren't disappointed.

Avik Roy, analyst with Monness Crespi Hardt, called the data "outstanding," while J.P. Morgan analyst Cory Kasimov wrote in a research note that the results were "encouraging, especially given the consistency across numerous different analyses."

The primary endpoint of the trial was a composite measurement of disease factors (SELENA SLEDAI score), disease worsening (PGA score) and organ involvement (BILAG-A/B scores). In addition to achieving statistical significance on the composite measurement, the high dose of Benlysta hit the mark on each individual component, while the low dose hit all but the BILAG-A/B portion.

Benlysta also delayed lupus flares, with a median time to flare of 119 days (p = 0.0036) for the high dose and 126 days (p = 0.0026) for the low dose compared to 84 days for placebo. The high dose also reduced the risk of having a flare.

Additionally, Benlysta patients were able to reduce their use of high-dose steroids, a finding that was significant for the low-dose Benlysta group (p = 0.025) and nearly significant for the high-dose Benlysta group (p = 0.053). Patients receiving high-dose Benlysta and lower steroid doses were able to avoid increasing their steroid use (p < 0.05). Quality of life improved for both the high-dose Benlysta (p = 0.025) and low-dose Benlysta (p = 0.027) groups at one year.

Kasimov noted that a "consistent separation" between treatment and placebo emerged early and was sustained throughout the year-long trial. He was particularly encouraged by the fact that a significant number of patients were able to reduce their steroid use by at least half as early as six months into Benlysta treatment.

Similarly, Roy pointed to statistically significant response rates that emerged as early as 16 weeks for the high-dose Benlysta group and 28 weeks for the low-dose Benlysta group, as well as disease improvements observed as early as week four.

Several analysts stated that the strength of the detailed data from HGSI's first Phase III study made them at least incrementally more positive on the outcome of the second Phase III trial. While the two trials are similar, the first was conducted primarily in Asia, South America and Eastern Europe while the second, which also is longer, was conducted primarily in North America and Europe.

Kasimov said that while HGSI did not initially break down its data geographically, which would help analysts handicap the second Phase III, that information may yet be provided in an analyst event scheduled for Tuesday evening.

If the data from the second trial are positive, HGSI and partner GlaxoSmithKline plc plan to submit a new drug application in the first half of 2010.

If approved, Piper Jaffray analyst Edward Tenthoff expects Benlysta to be widely used in lupus, due to its clean safety profile. Despite many failed attempts, there have been no new drugs approved for lupus in half a century, and the current standard of care involves harsh regimens of chemotherapy and steroids. Benlysta, an antibody targeting B-lymphocyte stimulator (BLyS), was well tolerated in the Phase III study with adverse event rates comparable to placebo.

Tenthoff wrote in a research note that he expects Benlysta sales to reach $6 billion by 2016. He also said an acquisition by GSK - which was rumored but never occurred after the initial Phase III data announcement - could still happen if the second trial is positive.

Shares of Rockville, Md.-based HGSI (NASDAQ:HGSI) slid 90 cents to close at $19.97 on Tuesday.

In other ACR conference news:

• Abbott, of Abbott Park, Ill., presented data showing that Humira (adalimumab) plus methotrexate decreased rheumatoid arthritis progression as well as joint swelling and tenderness over eight years of treatment. Humira is approved for RA, psoriasis, Crohn's disease and other conditions.

• Bristol-Myers Squibb Co., of New York, presented data from an open-label study of rheumatoid arthritis drug Orencia (abatacept) showing minimal immunogenicity with a subcutaneous formulation. The approved drug currently requires an intravenous loading dose.

• Celgene Corp., of Summit, N.J., presented data from an extension to its Phase II psoriatic arthritis trial of apremilast, which previously met its endpoint of significantly improving ACR20 at three months (43.5 percent for twice daily and 35.8 percent for once daily vs. 11.8 percent for placebo). The extension data showed that, after six months, 40 percent of twice-daily and 39.1 percent of once-daily patients achieved ACR20.

• Chelsea Therapeutics International Ltd., of Charlotte, N.C., presented Phase II data showing that CH-1504 has comparable efficacy to methotrexate in rheumatoid arthritis, and Phase I data showing that CH-4051 was well tolerated. Both drugs are metabolically inert antifolate molecules that inhibit dihydrofolate reductase.

• Emisphere Technologies Inc., of Cedar Knolls, N.J., reported Phase I results demonstrating that a single dose of oral parathyroid hormone PTH1-34, developed using the Eligen drug delivery technology, achieved potentially therapeutically relevant exposure and safety profiles to those of the currently available injectable formulation in healthy postmenopausal women. The product is partnered with Basel, Switzerland-based Novartis AG.

• NicOx SA, of Sophia Antipolis, France, presented detailed 26-week data from its second pivotal trial of naproxcinod for osteoarthritis showing naproxcinod was noninferior to naproxen. A new drug application is under FDA review. (See BioWorld Today, Sept. 28, 2009.)

Published  October 21, 2009