PII-059 - ASSESSMET OF SUBCUTANEOUS SITE OF INJECTION ON THE PK OF SOTATERCEPT

S. Ayalasomayajula¹, E. Bajwa², S. Hu³, Y. Zeng⁴, Z. Hu⁵, F. Gheyas⁶, I. Younis⁷; ¹MRL-TMED-QP2, Rahway, NJ, USA, ²MRL-TMED, Cambridge, MA, United State, ³Merck, Rahway NJ, USA, ⁴MRL-BARDS, Rahway, NJ, United States, ⁵Merck, MRL, Merck & Co., Inc., Rahway, NJ, USA, ⁶MRL-TMED-QP2, Rahway, NJ, United States, ⁷Merck, Rahway, NJ, USA.

Background: Sotatercept is a recombinant activin receptor type IIA fusion protein (ActRIIA) indicated for the treatment of pulmonary hypertension and is recommended for subcutaneous administration once every 3 weeks. Subcutaneous injections are administered via different sites including upper arm (left or right), abdomen, or thigh/other. The objective of this analysis is to determine the impact of site of subcutaneous administration on the PK of sotatercept.

Methods: The safety, PK, and efficacy of sotatercept was evaluated in patients with end stage renal disease following intravenous and subcutaneous administration of sotatercept Q4W (REN001; n=43 total: SC dose: 0.3 to 0.7 mg/kg or placebo) or Q2W (REN002; n=50 total; IV dose: 0.1 mg/kg to 0.4 mg/kg; SC dose: 0.13 mg/kg to 0.5 mg/kg ) (Coyne et al., 2019). The PK parameters (Tmax, T1/2, Cmax, AUC0-28, and AUC0-14) estimated following subcutaneous administration in these studies and corresponding site of injection data was considered for this evaluation. Dose-normalized PK parameters were compared in each study using descriptive statistics and box plots to assess the impact of site of injection on PK of sotatercept.

Results: While sc PK data was available from all 38 participants in REN001 study, 30 out of 50 participants completed REN002 study of which sc PK data was available from 14 participants. Dose linear increase in both Cmax and AUC were observed over the tested dose range of 0.13 mg/kg to 0.7 mg/kg irrespective of the site of injection. In REN001 study, both dose-normalized Cmax and AUC0-28 were comparable between abdomen injection (n=6), thigh/other (n=2), or upper arm (n=30) injections. Similarly, in REN002 study dose-normalized Cmax and AUC0-14 were comparable between abdomen (n=9) and upper arm (n=5) injections. Although Tmax appeared to be marginally higher with abdomen injection, T1/2 is comparable between abdomen and upper arm site of injections.

Conclusion: PK of sotatercept is consistent independent of site of injection.