Staff Writer

Shares of Human Genome Sciences Inc. popped 18 percent on Thursday after the company presented four-year follow-up data from its failed Phase II trial of lupus drug Benlysta (belimumab, formerly LymphoStat-B) at the 2009 Congress of the European League Against Rheumatism (EULAR).

The 449-patient Phase II trial originally missed its primary endpoints, but a subgroup of serologically active patients experienced a statistically significant improvement in lupus signs and symptoms at week 52. (See BioWorld Today, Oct. 6, 2005.)

The new data presented at EULAR followed about half of those patients through an open-label extension study from week 52 to week 208, during which time the response rate increased from 46 percent to 57 percent, the disease flare rate decreased from 62 percent to 16 percent, and the adverse event rate remained similar to placebo.

William Freimuth, HGS's vice president of clinical research, said the data reiterated Benlysta's "durability of efficacy" in the serologically active subgroup.

Edward Tenthoff, analyst with Piper Jaffray & Co., agreed that the findings were "encouraging" but noted in a research report that several caveats make it difficult to draw any conclusions about the two ongoing Phase III trials of Benlysta in lupus.

The first of those trials, BLISS-52, is expected to deliver data next month, with the second trial, BLISS-76, following in November. The double-blind, placebo-controlled studies are being conducted with partner GlaxoSmithKline plc under a special protocol assessment. (See BioWorld Today, Feb. 14, 2007.)

HGS used the hard lessons learned during its Phase II trial to design the Phase III studies. In an attempt to mirror the successful Phase II subset, the Phase III trials enrolled only serologically active patients and share a primary endpoint of patient response rate at week 52 as defined by a composite of measures that worked well in the Phase II trial.

Additionally, the 800-patient Phase III trials are larger and better powered, and the use of background standard-of-care medications is being more tightly controlled.

Freimuth explained that in order to succeed, the Phase III studies need to show roughly a 12 percent to 13 percent improvement in response rate at week 52 for Benlysta over placebo - although he added that there are fairly complicated statistical factors involved. In the Phase II subset at week 52, the response rate was 46 percent for Benlysta-treated patients and 29 percent for placebo-treated patients.

"So yes, it is a subgroup analysis and it is post hoc, but . . . if we see the same thing in Phase III that we saw in Phase II, then we'll win," Freimuth said.

It's a leap of faith that has proven risky for biotechs in general and for lupus in particular.

La Jolla Pharmaceutical Co., too, had a Phase II/III failure with lupus drug Riquent (abetimus sodium), but the company found statistical significance in a subgroup of high-affinity patients and pushed forward to Phase III, which also failed. A second Phase III trial tried to enroll more patients, use higher doses and better control background therapies, but it was stopped for futility. (See BioWorld Today, May 4, 2000, Feb 13, 2003, and Feb. 13, 2009.)

Other late-stage lupus failures include Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.), Prestara (prasterone, Genelabs Technologies Inc.) and CellCept (oral mycophenolate mofetil, Aspreva Pharmaceuticals Corp.). But several drug developers continue to set their sights on the autoimmune disease, which is treated with harsh regimens of chemotherapy and steroids, and hasn't seen a new drug approval in nearly half a century.

Among those still in trials are Orencia (abatacept, Bristol-Myers Squibb Co.), epratuzumab (UCB SA) and ocrelizumab (F. Hoffmann-La Roche Ltd.).

Freimuth said Benlysta is differentiated both by its endpoints and its mechanism. The drug is a human monoclonal antibody that inhibits B-lymphocyte stimulator, or BLyS, a protein involved in the growth and survival of certain B cells.

Removing BLyS allows the autoimmune B cells that were programmed to die to do so, but doesn't wipe out as many normal B cells as an approach like Rituxan, he explained.

Yet analysts remain skeptical. In a research note, Leerink Swann analyst Joseph Schwartz gave Benlysta a 60 percent chance of success, but JMP Securities LLC analyst Liisa Bayko wrote that due diligence with physicians leads her to believe the trials "will likely not work."

Ian Somaiya, analyst with Thomas Weisel Partners, wrote that he remains "cautious" on the outcome of the Phase III trials but maintains an "overweight" rating nonetheless, given that HGS's stock would probably only fall to $1 or $2 if the drug failed but could fly to $15 or $20 if it succeeds.

Shares of Rockville, Md.-based HGS (NASDAQ:HGSI) rose 48 cents on Thursday, to close at $3.19.

In other news reported at EULAR:

• Active Biotech, of Lund, Sweden, updated data from a concluded Phase Ib trial of the 57-57 SLE project. The patients in the Phase Ib trial for lupus were treated daily for 12 weeks with 57-57. The maximum tolerable dose was, as earlier communicated, defined at 4.5 mg/day. The overall safety profile throughout the study was favorable. The 57-57 compound is an oral immunomodulatory quinoline therapy for chronic lupus.

• Ardea Biosciences Inc., of San Diego, announced positive interim results from an ongoing Phase IIa, proof-of-concept study of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout, as well as additional positive results from completed Phase I studies of RDEA594 in normal, healthy volunteers.

• Pfizer Inc., of New York, said data from two new midstage clinical studies of the company's oral JAK-3 inhibitor, CP-690,550, showed statistically significant response vs. placebo for patients with rheumatoid arthritis. Data from these two Phase II trials and one ongoing open-label safety study are being presented this week, and they confirmed findings from two previously reported Phase II studies in RA and have been used to support dose selection for Phase III. Pfizer is partnered with Catalyst Pharmaceutical Partners, of Coral Gables, Fla. (See BioWorld Today, Jan. 9, 2007.)