Patients treated with Tenax Therapeutics’ heart failure drug TNX-103 did not show significantly better functional performance—though Leerink analysts found biomarker improvements and subgroup analyses in elderly and more severe patients “very encouraging.”
Tenax Therapeutics’ investigational heart failure drug failed to improve functional performance in a late-stage study.
The North Carolina biotech’s shares plunged 85% before the opening bell on Monday, hitting $1.99. The company’s previous closing price was $13.44.
Tenax is testing TNX-103 in the ongoing Phase 3 LEVEL trial of patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). The study’s primary endpoint, six-minute walk distance (6MWD) at 12 weeks, improved by 14 meters in those on TNX-103 versus 10.4 meters in placebo counterparts. The difference fell short of significance, according to a Monday morning announcement.
Improvements in symptom burden at 12 weeks was likewise not significantly different between the treatment groups.
These results are “very disappointing,” Leerink Partners told investors in a Monday note, partly blaming the “surprising” placebo response for the late-stage stumble. Still, the firm saw some glimmers of hope in Tenax’s readout, pointing to “very encouraging” biomarker data and informative subgroup results.
“Subgroup analysis suggests TNX-103 may benefit older and more severely affected patients,” the analysts continued, adding that these findings will help the biotech fine-tune the design of future trials.
Tenax CEO Chris Giordano agreed, and sees the entirety of LEVEL’s data as overall good for TNX-103, noting in a prepared statement that the readout “will guide us toward approval.” In particular, LEVEL’s findings “provide us with a key insight into the population that exhibits the treatment effect of TNX-103.”
Pre-specified analyses of the primary outcome measure, focusing on different patient subgroups, showed that the benefits of TNX-103 looked to be more pronounced in those who fell below the median 6MWD of 333 meters at baseline. At 12 months, these patients saw a 26.3-meter improvement as compared to placebo, which achieved nominal significance.
TNX-103 also appeared more effective in older patients, eliciting nominally significant 12-week improvements in functional performance in patients 71 years and above, according to Tenax.
The company also dug into biomarker findings with additional pre-specified exploratory analyses, touting a nominally significant 49% reduction in NT-proBNP, a key indicator of cardiac stress and a major prognostic factor in heart failure, versus placebo. Decrease in right ventricular systolic pressure was also greater in patients treated with TNX-103.
As for safety, side effects occurred more frequently in patients given TNX-103, though serious adverse events were balanced between the treatment groups. Tenax did not flag an increased risk of arrhythmia associated with the drug.
Given LEVEL’s outcomes, the biotech now plans to meet with the FDA to tweak the study’s protocol and include more patients with severe disease “to ensure a robust treatment effect,” according to the Monday announcement.
“Given positive signals from LEVEL, TNX-103’s acceptable safety profile, and the large unmet need in HFpEF, regulatory authorities would likely work with the company to modify [the protocol] to allow enrichment for more severe patients,” Leerink said on Monday.
Tenax is also testing TNX-103 in the Phase 3 LEVEL-2 study of PH-HFpEF, though the biotech did not say in its release whether that study’s protocol would be amended as well.
