Two Phase 2 studies in patients with chronic coronary syndromes and AMI, respectively, assessed the effect of subcutaneous administration of selatogrel on the pharmacodynamic objective of inhibiting platelet aggregation (Storey et al. 2020; Sinnaeve et al. 2020).† The chart below shows the inhibition of platelet aggregation following subcutaneous injection. In patients with chronic coronary syndromes, an injection site reactions occurred in 9.6% and 4.3% with selatogrel 8 and 16 mg, respectively, vs. 6.9% with placebo. Transient dyspnea (all cases were mild except one patient on 16 mg dose who had moderate dyspnea) occurred in 5.3% and 8.7% of patients with the 8 mg and 16 mg dose, respectively, compared to none with the placebo.

Adapted from Storey et al. 2020

Study Title:
Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Self-administered Subcutaneous Selatogrel for Prevention of All-cause Death and Treatment of AMI in Subjects With a Recent History of AMI.

Brief Summary:
The purpose of this study is to assess the clinical efficacy of selatogrel when self-administered upon occurrence of symptoms suggestive of an AMI in participants at risk of having a recurrent AMI.

Eligible subjects will be randomized 1:1 into one of the two groups:

^†Self-administration encompasses the use of the autoinjector by another person (e.g., partner, close relative, friend, caregiver) who may be called for help during the emergency situation of a suspected AMI.

Study Population:
Adult (≥18 year of age) diagnosed with symptomatic type 1 AMI ST-Elevation Myocardial Infarction (STEMI) or Non-ST-Elevation Myocardial Infarction (NSTEMI) within 4 weeks prior to randomization. Additionally, subject must be diagnosed with multivessel coronary artery disease (defined as ≥50% stenosis on 2 or more coronary artery territories or on the left main artery during a prior cardiac catheterization or cardiac catheterization during the qualifying AMI event), having presence of ≥2 additional cardiovascular risk factors (second prior AMI, diabetes mellitus, chronic kidney disease, peripheral artery disease, or unsuccessful coronary revascularization of the qualifying AMI) but not be at an increased risk of serious bleeding.

Subjects must be able to successfully self-administer placebo according to the autoinjector instruction for use during screening.

Study Objective:
The overall objective of this study is to assess the clinical efficacy of Selatogrel when self-administered upon occurrence of symptoms suggestive of an AMI in participants at risk of having a recurrent AMI.

Outcome Measures:
The Primary Outcome Measures:

1. Clinical status assessed using a 6-point ordinal scale after any study treatment self-administration. The worst clinical outcome will be retained as the primary efficacy outcome. The 6 mutually exclusive outcomes ranked from worst to best are:
   1. Death (all causes) within 7 days after study treatment administration.
   2. AMI with compromised electro-hemodynamics, within 2 days after study treatment administration.
   3. STEMI within 2 days after study treatment administration.
   4. High-risk NSTEMI, within 2 days after study treatment administration.
   5. NSTEMI with peak cardiac troponin >10 times upper limit of normal, within 2 days after study drug administration.
   6. None of the above
2. Occurrence of type 3 or type 5 treatment-emergent bleeding events assessed according to the Bleeding Academic Research Consortium (BARC) definition (Mehran et al. 2011), within 2 days after study treatment administration.

The Secondary Outcome Measures:
Composite endpoint of death, non-fatal AMI, hospitalization or unplanned emergency department visit for heart failure within 30 days after any self-administration.

References:

Zenklusen, I., Hsin, C. H., Schilling, U., Kankam, M., Krause, A., Ufer, M., &Dingemanse, J. (2022). Transition from Syringe to Autoinjector Based on Bridging Pharmacokinetics and Pharmacodynamics of the P2Y12 Receptor Antagonist Selatogrel in Healthy Subjects. Clinical pharmacokinetics, 61(5), 687–695

Sinnaeve, P., Fahrni, G., Schelfaut, D., Spirito, A., Mueller, C., Frenoux, J. M., Hmissi, A., Bernaud, C., Ufer, M., Moccetti, T., Atar, S., & Valgimigli, M. (2020). Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction. Journal of the American College of Cardiology, 75(20), 2588–2597.

Storey, R. F., Gurbel, P. A., Ten Berg, J., Bernaud, C., Dangas, G. D., Frenoux, J. M., ... &Angiolillo, D. J. (2020). Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes. European Heart Journal, 41(33), 3132-3140.

Mehran, R., Rao, S. V., Bhatt, D. L., Gibson, C. M., Caixeta, A., Eikelboom, J., Kaul, S., Wiviott, S. D., Menon, V., Nikolsky, E., Serebruany, V., Valgimigli, M., Vranckx, P., Taggart, D., Sabik, J. F., Cutlip, D. E., Krucoff, M. W., Ohman, E. M., Steg, P. G., & White, H. (2011). Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation, 123(23), 2736–2747.

The information is intended for HCPs to register their interest to become an investigational site in the study.

†The analysis and associated p values need to be cautiously interpreted due to the small study population size. Another limitation is the open-label design of the study and the absence of a placebo arm. Given the population of subjects with AMI, it was deemed unethical to administer placebo, especially to subjects with STEMI for whom early administration of an oral P2Y12 receptor antagonist is recommended by guidelines.

*SOS-AMI study (NCT04957719. Updated October 10, 2024. Available at: https://clinicaltrials.gov/study/NCT04957719?cond=NCT04957719&rank=1. Accessed November 1, 2024) has received Fast Track designation from the US FDA.

Note: The sponsor of the named study is currently Idorsia Pharmaceuticals Ltd. As of March 18, 2024, Viatris entered into a global collaboration with Idorsia, which includes Selatogrel, and the study sponsorship is expected to be transferred to Viatris during the course of 2025.

Viatris, Robert J. Coury Global Center, 1000 Mylan Blvd., Canonsburg, Pennsylvania 15317, United States