CARY, N.C. and BASEL, Switzerland — Oct. 22, 2019 — Altavant Sciences, a clinical-stage biopharmaceutical company focused on patient-centric drug development in rare respiratory diseases, today announced mechanistic preclinical pharmacodynamic and Phase 1 data supporting once-daily dosing of rodatristat ethyl for the treatment of pulmonary arterial hypertension (PAH). These data were presented as a poster delivered as a short oral presentation, entitled “Once Daily Oral Dosing of Rodatristat Ethyl (RVT-1201) Achieves Reductions in Serotonin Biosynthesis Comparable to those Associated with Reversal of Vascular Remodeling in PAH Animal Models” (poster E1090), at the American College of Chest Physicians’ CHEST Annual Meeting 2019 in New Orleans.
The safety and activity of rodatristat ethyl were compared when administered either once-daily (500mg QD or 800mg QD) or twice-daily (200mg BID or 400mg BID) to 48 healthy subjects (36 active: 12 placebo) over 14 days of treatment. Reductions in peripheral serotonin, a potential mechanistic efficacy biomarker in PAH, were assessed by the measurement of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin and a biomarker of serotonin biosynthesis. Daily doses were selected to approximate similar exposure for 800 mg QD versus 400 BID and 500 mg QD versus 200 mg BID. Following 14 days of treatment, comparable reductions in urinary 5-HIAA were seen for each daily dose. Both daily exposure levels provided a degree of 5-HIAA reduction that is consistent with marked improvements in vessel remodeling in preclinical models of PAH.
Rodatristat ethyl has demonstrated favorable safety and tolerability across two Phase 1 studies in healthy volunteers. Altavant is currently investigating rodatristat ethyl in its ongoing ELEVATE 1 proof-of-concept Phase 2a study in patients with PAH.
William T. Symonds, Pharm.D., chief executive officer of Altavant commented, “Patients with PAH often take one or more medications daily to treat their disease and manage symptoms. The ability to offer rodatristat ethyl in a once-daily dosage form would allow patients the flexibility to integrate it into their existing treatment regimen more easily, potentially improving overall treatment convenience and adherence.”
About Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by vasoconstriction, cellular proliferation and remodeling in the small pulmonary arteries. These changes lead to high arterial pressure, right heart strain, and ultimately, right heart failure and death. Although there are approved treatments used for PAH, they mainly help alleviate symptoms, primarily via vasodilation, and none reverse the disease process. Long-term survival rates for PAH are poor, with less than 40 percent survival at five years for high-risk patients.
About Rodatristat Ethyl
Rodatristat ethyl is a tryptophan hydroxylase (TPH) inhibitor designed to reduce the body’s peripheral production of serotonin. A significant body of scientific evidence supports dysregulated peripheral serotonin production as a trigger of aberrant proliferation and constriction of the smooth muscle cells in the wall of the pulmonary arteries, causing them to restrict blood flow in pulmonary arterial hypertension (PAH). By lowering circulating serotonin levels, it is believed that rodatristat ethyl may halt or reverse the pathology of diseases that are driven by excessive serotonin production, such as PAH, idiopathic pulmonary fibrosis (IPF) and sarcoidosis. Altavant is currently testing this mechanism of action in the ELEVATE 1 proof-of-concept Phase 2a study of rodatristat ethyl in patients with pulmonary arterial hypertension (PAH).
About Altavant Sciences
Altavant Sciences is a clinical-stage biopharmaceutical company focused on elevating patient-centric drug development in rare respiratory diseases with an initial focus on pulmonary arterial hypertension (PAH). Altavant’s lead candidate, rodatristat ethyl, is a tryptophan hydroxylase (TPH) inhibitor that reduces the body’s peripheral production of serotonin, thereby lowering circulating serotonin levels in diseases where excessive production of the hormone has been implicated in pathogenesis – including PAH, certain types of cancer, GI disorders, fibrosis and inflammation. Rodatristat ethyl is currently being investigated in the ELEVATE 1 Phase 2 Study in patients with PAH. For more information, please visit www.altavant.com.
About Roivant Pharma
Roivant Pharma is the biopharmaceutical business unit of Roivant Sciences. Roivant Pharma is focused on end-to-end biopharmaceutical company creation, launch, and oversight. Roivant Pharma companies include Altavant, Aruvant, Axovant, Dermavant, Enzyvant, Genevant, Immunovant, Metavant, Myovant, Respivant, Urovant, and Arbutus.
About Roivant Sciences
Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. Roivant does this by building Vants – nimble, entrepreneurial biotech and healthcare technology companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. For more information, please visit www.roivant.com.