1. Theravance Biopharma presented Phase 3 results at a major congress. 2. Ampreloxetine improved nOH symptoms in MSA patients significantly. 3. Study findings support ongoing registrational study for nOH and MSA. 4. MSA patients show high unmet need for effective nOH therapies.
The positive Phase 3 results for ampreloxetine signal strong market potential, akin to past successful drug launches in rare diseases. For example, other rare disease treatments have seen stock spikes following positive trial results.
Given ampreloxetine's potential to address significant unmet needs in nOH patients, the findings are highly relevant and favorable for TBPH's future prospects.
The ongoing registrational study could lead to FDA approval, potentially increasing revenue streams long-term, similar to other firms successfully launching new therapies.
"Theravance Biopharma" or the "Company" (NASDAQ: TBPH) today announced presentation of analyses of its previous Phase 3 program evaluating ampreloxetine, an investigational medicine for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) at the International MSA Congress, taking place May 9-11 in Boston, Massachusetts.
A subgroup analysis selected as a platform presentation focused on patients with Multiple System Atrophy (MSA) in the REDWOOD 0170 study (NCT03829657), an international phase 3, placebo-controlled, double-blind, randomized withdrawal trial, designed to demonstrate clinical worsening in those assigned to placebo. This analysis concluded:
An additional analysis from Study 0169 (NCT03750552) presented at the Congress showed that despite treatment with available nOH medications, patients with MSA had the highest nOH symptom burden on entry, which highlights the substantial unmet need for better nOH therapies in this population.
Results from these studies were supportive of the current registrational study in patients with nOH and MSA that is currently ongoing (CYPRESS, NCT05696717).
"Patients with MSA often experience severe symptoms and impact to their quality of life due to nOH, and we are motivated to reduce this burden to patients and their caregivers," said Dr. Lucy Norcliffe-Kaufmann, Theravance Biopharma's Executive Director of Clinical Science. "As supported by a clinically-validated measure of patient well-being over 16 to 22 weeks of therapy, these analyses underpin our belief in ampreloxetine's potential to provide durable symptom relief with clinically meaningful outcomes."
Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The unique benefits of ampreloxetine treatment reported in MSA patients from Study 0170 included an increase in norepinephrine levels, a favorable impact on blood pressure, clinically meaningful and durable symptom improvement, and no signal for worsening of supine hypertension. In the US, the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication.
Study 0197 (NCT05696717) is currently enrolling. This is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. The Study includes four periods: screening, open label (12-week period, participants will receive a single daily 10 mg dose of ampreloxetine), randomized withdrawal (eight-week period, double-blind, placebo-controlled, participants will receive a single daily 10 mg dose of placebo or ampreloxetine), and a long-term treatment extension. Secondary outcome measures include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) item 1 (activities that require standing for a short time) and item 3 (activities that require walking for a short time).
Study 0169 (NCT03750552) was a Phase 3, 4-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ampreloxetine compared to placebo in patients with symptomatic nOH (n=195). Patients from Study 0169 were eligible to enter into Study 0170 (NCT03829657), a Phase 3, multi-center, 22-week study comprising a 16-week open-label period and a 6-week double-blind, placebo-controlled, randomized withdrawal period to evaluate the sustained benefit in efficacy and safety of ampreloxetine in patients with symptomatic nOH. The primary endpoint for Study 0170 of treatment failure at week 6 was defined as a worsening of both Orthostatic Hypotension Symptom Assessment Scale (OHSA) question #1 and Patient Global Impression of Severity (PGI-S) scores by 1.0 point. After Study 0169 did not meet its primary endpoint, the Company took actions to close out the ongoing clinical program including Study 0170. The study was more than 80% enrolled (n=128/154 planned) despite stopping early. The primary endpoint was not statistically significant for the overall population of patients which included patients with Parkinson's disease, pure autonomic failure and MSA (odds ratio=0.6; p-value=0.196). The pre-specified subgroup analysis by disease type suggests the benefit seen in patients receiving ampreloxetine was largely driven by MSA patients (n=40). An odds ratio of 0.28 (95% CI: 0.05, 1.22) was observed in MSA patients indicating a 72% reduction in the odds of treatment failure with ampreloxetine compared to placebo. The benefit to MSA patients was observed in multiple endpoints including OHSA composite, Orthostatic Hypotension Daily Activities Scale (OHDAS) composite, Orthostatic Hypotension Questionnaire (OHQ) composite and OHSA #1 (read more about the data here).
MSA is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary. One of the most frequent autonomic symptoms associated with MSA is a sudden drop in blood pressure upon standing (nOH). There are approximately 50,000 MSA patients in the US and 70-90% of MSA patients experience nOH symptoms. Despite available therapies, many MSA patients remain symptomatic with nOH.
Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a fall in systolic blood pressure of ≥20 mm Hg or diastolic blood pressure of ≥10 mm Hg, within 3 minutes of standing. Severely affected patients are unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope. A debilitating condition, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision, weakness, trouble concentrating, and head and neck pain.
Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value.
For more information, please visit www.theravance.com.