Contributing Writer

Before the end of the year, Human Genome Sciences Inc. plans to kick off two Phase III trials of Albuferon (albumin-interferon alpha 2b), a long-acting form of interferon alpha, in chronic hepatitis C virus (HCV).

Both studies, already approved by regulatory authorities in the U.S. and Europe, will be randomized, open-label, active-controlled, multi-center trials designed to establish the non-inferiority of Albuferon compared to Pegasys (pegylated interferon alfa-2a) from F. Hoffmann-La Roche Ltd., of Basel, Switzerland. The trials will evaluate safety, efficacy and quality of life, with a primary endpoint of sustained virologic response, defined as undetectable HCV RNA viral load (<10 IU/mL) at 24 weeks after treatment ends. The ACHIEVE 1 trial will enroll at least 1,278 HCV genotype 1 patients for 48 weeks of treatment, while the ACHIEVE 2/3 trial will enroll at least 918 HCV genotype 2 and 3 patients for 24 weeks of treatment.

In both trials, patients will be treatment-na ve and will receive ribavirin along with Albuferon (900 mcg or 1,200 mcg) every two weeks or Pegasys (180 mcg) every week.

In a presentation to analysts and investors in New York, HGS reiterated that Albuferon has shown comparable safety and efficacy to pegylated interferon in Phase II trials, but with dosing every two weeks rather than every week - an important difference for patients struggling with the side effects of interferon treatment, the company said. Interferon is the standard of care for chronic HCV, creating a $2 billion U.S. market.

When asked why the company is dosing Albuferon at both 900 mcg and 1,200 mcg, Executive Vice President of Drug Development David Stump said that although the trial is designed to show non-inferiority, the company expects to have "a real shot" in the 1,200-mcg dose at achieving not just non-inferiority, but superiority over Pegasys.

Even if the trials demonstrate only non-inferiority, HGS said its market research shows Albuferon's dosing schedule could allow it to become the interferon of choice. The company in 2007 plans to initiate a Phase IIb trial of Albuferon dosed once a month.

Albuferon, which results from the genetic fusion of human albumin and interferon alpha 2b, is partnered with Novartis AG. When the first patient in the Phase III program is dosed, HGS expects to receive a $47.5 million milestone payment from Novartis as part of a deal that could eventually bring the Rockville, Md.-based company $550 million in fees and payments. (See BioWorld Today, June 7, 2006.)

HGS president and CEO Thomas Watkins said the collaboration with Novartis "will essentially cut the cost of these [Albuferon Phase III] programs in half."

Cost-cutting is a familiar theme at HGS these days, where a combination of clinical cost-sharing with partners, increased revenues, consolidation of locations and tight spending control have reduced the annual burn rate from $230 million in 2005 to an estimated $75 million to $125 million this year. Going forward, the company expects to burn through about $150 million annually for the next several years.

In addition to Albuferon, HGS' other primary focus is LymphoStat-B (belimumab), which is expected to begin two Phase III trials this year for lupus. U.S. and European regulatory agencies have approved the major components of the protocols, and the company is awaiting feedback from the FDA regarding its submission for a special protocol assessment. (See BioWorld Today, Aug. 10, 2006).

LymphoStat-B, which is partnered with GlaxoSmithKline plc, is a human monoclonal antibody that inhibits BLyS (B-lymphocyte stimulator), a protein that may contribute to the production of autoantibodies correlating with disease severity in lupus.

A Phase II study of LymphoStat-B missed its primary endpoints of reducing lupus signs and symptoms at week 24 and increasing the time to first lupus flare over a 52-week period, but the drug showed statistically significant positive results in a subset of 75 percent of patients in the trial. (See BioWorld Today, Oct. 6, 2005.)

HGS also announced progress with ABthrax (raxibacumab), a human monoclonal antibody that prevents anthrax toxins from entering and killing cells.

The U.S. government exercised its option to purchase 20,000 doses of ABthrax for the Strategic National Stockpile in June 2006. HGS expects to receive about $165 million from that deal, with more than 90 percent of it to come in 2008 upon meeting the terms for delivery.

Late last week, HGS announced positive Phase I results with HIV drug candidate HGS004. HGS' pipeline also includes drug candidates and programs for cancer and rheumatoid arthritis, as well as programs with GlaxoSmithKline for cardiovascular disease, bone disorders and diabetes.