Faron fingers low bioactivity as possible cause of phase 3 flop

Faron Pharmaceuticals has zeroed in on low levels of interferon-beta bioactivity to explain why its phase 3 traumakine trial failed comprehensively. The biotech is now testing product batches to assess whether the formulation is to blame for the lackluster data.

Early biomarker analysis suggests the level of interferon-beta bioactivity in the phase 3 differed from that seen in a previous phase 1/2 trial. Traumakine is a recombinant form of interferon-beta-1a. Faron thinks interferon-beta-1a enhances CD37 expression, triggering events that curb the vascular leaking and inflammation that affect patients with acute respiratory distress syndrome (ARDS).

Lower-than-expected interferon-beta activity would undermine the first step in that process, leading to poor patient outcomes. Faron is now working to identify the cause of the activity level.

The investigation is looking at product batches to see if a formulation issue is responsible. Other avenues of investigation include administration and deactivation. At this stage it is unclear whether Faron will establish a convincing explanation for the failure. Even if to does, Faron may still struggle to plot a course back from a blow that wiped 80% off its stock price.

Turku, Finland-based Faron proceeded confidently into a pivotal ARDS study in the back of data from a phase 1/2 trial that linked traumakine to positive outcomes. But the pivotal 300-patient study failed to replicate the results of the smaller, earlier trial. Traumakine was no better than placebo at keeping patients alive and off ventilators.

Faron initially identified an "unusually low mortality rate" in the placebo arm as the possible culprit. All-cause mortality at 28 days in the control cohort of the phase 3 was nine percentage points lower than in the earlier study.

That is at best a partial explanation for the failure, though, as the mortality in the treatment arm was far higher in the phase 3 than the earlier trial. The 28-day all-cause mortality rate in the traumakine arm of the phase 1/2 was 8%. In the phase 3 trial, the figure was 26.4%, higher than was reported in the control arm.

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