Disappointment for Genentech/Actelion as Veletri trial misses target

Actelion and Genentech's dual endothelin receptor antagonist Veletri(tezosentan) has achieved disappointing results in the RITZ-1 trial, involving patients with acute heart failure, raising questions about the prospects of this leading compound in a new therapeutic category.

Genentech's share price dropped 8% on the day of the announcement (April 20) to $52.00, while Actelion's stock lost just over 62% to close at 220 Swiss francs. However, the impact of the decline, at least for Genentech, was mitigated by the fact that positive data on Veletri has already been reported in another Phase III trial, RITZ-2 (Marketletter March 26). Analysts have also suggested that Veletri, with a peak revenues potential of around $100 million, is of marginal importance to Genentech, although it clearly has far more significance for a firm like Actelion, which currently has no revenue stream.

The 675-patient RITZ-1 study, which was designed to evaluate the ability of Veletri plus standard treatment to reduce the clinical symptoms of AHF, based on the patient's assessment of dyspnea, failed to show an effect on either this variable or secondary endpoints, including time to death or worsening of heart failure. This conflicts with the 292-patient RITZ-2 trial results, which demonstrated statistically-significant hemodynamic benefits in its primary efficacy measure, an improvement in cardiac index six hours after infusion of the drug, compared to placebo.