Knoll is considering the next step for its TNF inhibitor Segard, after one of two pivotal trials for sepsis showed a modest mortality benefit.

The company maintained that it is encouraged by the results of the just-completed MONARCS trial, which found that Segard (afelimomab) reduced by 6.9% the relative risk of all-cause 28-day mortality in 998 sepsis patients with elevated levels of interleukin-6.

Knoll said it is completing an in-depth review of the MONARCS data to determine the next steps regarding submission of an application for the drug. Knoll previously said it hoped for a 2001 launch.

Knoll did not say whether the mortality benefit in the MONARCS trial was statistically significant. An earlier study (RAMSES) showed a non-significant trend towards a mortality benefit with Segard of about the same size seen in the MONARCS trial.

Knoll is pursuing a novel strategy in developing Segard. The two pivotal trials used a bedside IL-6 blood level test (Septest) to select patients for therapy. Knoll hopes to market both the drug and the diagnostic.

Knoll enrolled 2,634 patients in the MONARCS trial, of whom 998 had elevated IL-6 levels and were randomized to afelimomab or placebo. The RAMSES study enrolled 944 patients, of whom 446 showed elevated IL-6 levels and were randomized to therapy or placebo.

Mortality rates in the RAMSES trial were 54% for Segard patients vs. 57.7% for placebo. The effect on mortality did not reach statistical significance. In fact, the trial was terminated early after an interim analysis showed it would be unlikely to reach a significant result.

The RAMSES trial did find a statistically significant difference in survival among patients with lower levels of IL-6 versus those with high levels who qualified for randomization.

While many sepsis agents have failed in late stage development, sepsis may be re-emerging as a high-profile disease target. A recent announcement regarding positive data for Lilly's sepsis candidate Zovant sent the company's stock up 15% (¹ Also see "Lilly Sepsis Trial Prompts Biotech-Style Jump In Second Quarter" - Pink Sheet, 10 July, 2000.).

Knoll Considering Segard Plans; Sepsis Study Shows Small Mortality Benefit

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