Basel, Switzerland and Durham, N.C. – Jan. 31, 2019 – Altavant Sciences, a company in the Roivant family focused on clinical development of novel therapies for pulmonary arterial hypertension (PAH) and other indications, will present its latest nonclinical and clinical data at the Pulmonary Vascular Research Institute (PVRI) 13th Annual World Congress on Pulmonary Vascular Disease, taking place in Barcelona, Spain from January 30 to February 3, 2019. These results provide additional evidence that treatment with rodatristat ethyl* facilitates vascular remodeling and ameliorates PAH in animal models. Further, in healthy individuals, oral rodatristat ethyl was generally well tolerated and generated biomarker findings comparable with those associated with efficacy in nonclinical studies. Together, these results support Altavant’s planned Phase 2 clinical program, which is expected to commence in the first half of 2019.
“PAH is a rare disease that remains a significant healthcare burden, with an approximate 50% five-year mortality rate despite over 14 available medications,” said William T. Symonds, Pharm.D., Chief Executive Officer of Altavant. “Current pharmacological care consists mainly of vasodilators, which provide only modest efficacy and do not specifically address the vessel remodeling believed to be responsible for the disease’s still unaddressed high morbidity and mortality. Nonclinical data generated to date suggest that by reducing serotonin through a novel mechanism of action, rodatristat ethyl may provide a disease-modifying therapy that could improve symptoms and survival rates in patients. Altavant looks forward to confirming these improvements through its planned and future clinical trials.”
Serotonin has been implicated in the pathogenesis of PAH, a disorder associated with increased pulmonary vascular remodeling that, left untreated, progresses rapidly to heart failure and death. Nonclinical data which will be presented at PVRI demonstrates that the median effective dose of rodatristat ethyl reduced serotonin biosynthesis by approximately 50% and had a positive effect on vessel remodeling in a rat model of PAH, as evidenced by a reduction in pulmonary vessel wall thickness. Combination therapy with ambrisentan in the nonclinical model led to further reductions in wall thickness.
Interim analysis of an ongoing dose-ranging, repeat-dose clinical study in healthy participants demonstrated dose-proportional increases in exposure following administration of rodatristat ethyl as an immediate-release tablet with food. In this study, and a previous study in healthy volunteers, all doses were generally well tolerated, with no serious adverse events or dose-limiting toxicities identified. Comparable biomarker results were observed across the studies where mid-level doses (400 mg twice daily) of rodatristat ethyl reduced urine levels of 5 hydroxyindoleacetic acid (5 HIAA), the main metabolite of serotonin and biomarker of serotonin biosynthesis, by approximately 50%. In nonclinical models a 50% reduction in 5-HIAA was associated with marked improvements in wall thickness.
Pharmacokinetic analyses predict that a clinical dose of 400 to 600 mg twice daily should achieve the target exposure affording at least a 50% reduction in serotonin biosynthesis.
Dr. Symonds concluded: “The results presented at PVRI, especially the biomarker findings, suggest that rodatristat ethyl has successfully engaged its target, lowering peripheral serotonin levels by a degree that we believe will be clinically meaningful. We look forward to further characterizing its activity in PAH patients in our planned clinical program.”
Poster details: Wring S, Alonso-Galicia M, Crizer KR, Gaukel E, Holman N, Pack T, Palacios M, Rurka J, Carpenter D, Rhodes M. Translational Analysis of RVT-1201 Nonclinical and Clinical Pharmacokinetic and Pharmacodynamic Biomarker Data to Predict Clinical Dose of a Novel TPH Inhibitor for Treatment of Pulmonary Arterial Hypertension. 13th PVRI Annual World Congress on PVD; 2 February 2019; Barcelona, Spain.
*name applied for; application pending
About Altavant Sciences
Altavant Sciences is a clinical stage biopharmaceutical company formed in 2018 to advance promising therapies in areas of high unmet medical need with an initial focus on pulmonary arterial hypertension. Altavant’s lead candidate is rodatristat ethyl*, 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 pulmonary arterial hypertension, certain types of cancer, GI disorders, fibrosis, and inflammation. Altavant is preparing rodatristat ethyl for Phase 2 clinical development in pulmonary arterial hypertension with additional indications being explored. The company is led by William T. Symonds, Pharm.D., who was formerly Chief Development Officer of Roivant.
Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. We do 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.