Tenax Therapeutics announced poor results Monday from a crucial Phase 3 trial of its experimental oral treatment for heart failure, causing the company ‘ s stocks to plummet more than 85 percent during the first trading session. The drug, called TNX-103, was unable to demonstrate any statistically-significant alleviation in the walk distance of patients suffering from aresistant form of the disease. The LEVEL trial (NCT00488906) evaluated the use of TNX-103 (levosimendan oral) on people suffering from pulmonary hypertension tied to the much rarer heart failure with preserved ejection fraction, or PH-HFpEF.
PH-HFpEF refers to type of the former that also has the latter, where the vasculature in the lungs is under elevated blood pressure while the heart pumps normally but exhibits stiff muscles that are hard to fill. Given such a broad primary endpoint of change in six-minute walk distance after 12 weeks of therapy: baseline, on-treatment improvement with TNX-103 was a non-statistically significant 14 meters and with placebo was 10.4 meters.
The 3.5 meter differential was not at all significant. The other main secondary measure, a self-administered symptom and life quality audit using the Kansas City Cardiomyopathy Questionnaire, again showed virtually no difference between the two arms: Although the drug missed on the primary endpoint, Tenax noted trends in some of the secondary and exploratory endpoints.
The patients who entered the study with more limited walking abilitythe 319 who covered less than the median of 333 meters in six minutesimproved 26 meters more than placebo. For the entire study population, the drug resulted in a 49 percent greater reduction in NT-proBNP, a blood indicator of cardiac stress and a a small, but quantifiable, fall in right ventricular systolic pressure.
The company called these proof of ‘biological activity, Mostly in patients with higher disease burden. Safety: was acceptable. There was a tolerability profile for TNX-103 that was similar to placebo and no new safety signals. The incidence of serious adverse events and of episodes of clinical worsening appeared to be balanced between the treatment and placebo groups although overall adverse events and adverse events considered to be treatment related appeared higher with active therapy. Tenax said it intends to seek a meeting with the FDA to discuss potential changes to its development strategy.
Several executives said the trial may have included too many patients with earlier disease and that a more targeted, late-stage population could still offer a way forward. An open-label extension to the trial remains in progress. The outcomes are a blow to this small biotech company whose inherent value was all the more dependent on this program.
PH-HFpEF is still an unmet medical need of intense focus and this trial has been followed as one of the more promising solutions. While the primary endpoint failure overall is unquestionable, the subgroup analysis and biomarker results keep the prospect alive that this agent may find a place with a new trial of better defined patients.
