Theravance Biopharma’s losing streak is going on and on and on. After going 0 for 3 last year, the biotech added another failure to its portfolio late Monday when it disclosed a phase 3 flop in a blood pressure disorder and pointed to a subgroup analysis as a potential path forward.
The latest data come from a study of norepinephrine reuptake inhibitor ampreloxetine in patients with neurogenic orthostatic hypotension, a disorder characterized by sustained falls in blood pressure shortly after standing up. Theravance randomized 128 patients to receive ampreloxetine or placebo to evaluate the effect of the drug on a primary treatment failure endpoint made up of two disease scores.
Ampreloxetine was no better than placebo against the primary endpoint. While the p-value came in at a non-significant 0.196, Theravance looked past the headline failure and zeroed in on the results from the pre-specified analysis of a subgroup of 40 patients with multiple system atrophy (MSA).
In the subgroup, the odds ratio came in at 0.28, compared to 0.6 in the overall study population. Digging deeper, Theravance found the suggestion that ampreloxetine may work in MSA was driven by changes in symptoms such as head discomfort and trouble concentrating.
“Ampreloxetine appears to improve a narrow, but critically important group of symptoms related to blood pressure control, and along with the safety profile, may represent a potential therapy for MSA patients,” Roy Freeman, M.D., a professor of neurology at Beth Israel Deaconess Medical Center who assisted in the design and interpretation of the study, said in a statement.
In light of the subgroup data, Theravance is starting talks with potential strategic partners and planning talks with health authorities to drive development of ampreloxetine in MSA. The program sits outside of Theravance’s current R&D focus, which was narrowed to respiratory diseases after the failure of another phase 3 trial of ampreloxetine last year.