PI-070 - IMPACT OF EAST ASIAN ETHNICITY ON PHARMACOKINETICS OF SOTATERCEPT

X. YU¹, J. XU¹, X. REN¹, L. ZHAN¹, M. KAKARA², T. HIRANO³, C. HASEGAWA³, X. LI⁴, H. XU⁴, E. Bajwa⁵, S. Ayalasomayajula⁶, I. YOUNIS⁷; ¹MSD R&D (China) Co., Ltd., Shanghai, Shanghai, China, ²MSD K. K., Tokyo, Tokyo, Japan, ³MSD K.K., Tokyo, Tokyo, Japan, ⁴Zhongshan Hospital Fudan University, Shanghai, Shanghai, China, ⁵MRL-TMED, Cambridge, MA, United State, ⁶MRL-TMED-QP2, Rahway, NJ, USA, ⁷MRL-TMED-QP2, Rahway, NJ, United States.

Background: Sotatercept, a first-in-class recombinant activin receptor type IIA fusion protein (ActRIIA), indicated for the treatment of pulmonary arterial hypertension (PAH). The objective of this work is to assess the impact of East Asian ethnicity on the pharmacokinetic (PK) of sotatercept.

Methods: Sotatercept safety and PK was evaluated in Japanese and Chinese healthy participants following single dose administration of 0.3 mg/kg or 0.7 mg/kg and in Global healthy participants following multiple dose administration of 0.3 mg/kg and 1 mg/kg. The PK (Cmax, AUC, Tmax, t1/2) of sotatercept in East Asian and Global participants is compared using descriptive statistics.

Results: The PK of sotatercept was obtained from 16 Global healthy participants (n=8 each at 0.3 mg/kg and 1 mg/kg), 20 Japanese healthy participants (n=10 each at 0.3 mg/kg and 0.7 mg/kg), and 17 Chinese healthy participants (n=9 at 0.3 mg/kg and n=8 at 0.7 mg/kg). Comparable exposure observed across Global, Japanese, and Chinese participants at 0.3 mg/kg dose levels. Moreover, the PK of sotatercept in Global healthy participants at 1 mg/kg normalized to the 0.7 mg/kg dose is comparable to that observed in Japanese, and Chinese healthy participants.

Conclusion: The PK of sotatercept is comparable among Japanese, Chinese, and Global healthy participants. Therefore, East Asian ethnicity does not impact on PK of sotaterept.