No, there is currently no FDA-approved oral PCSK9 inhibitor available for clinical use.
All currently approved PCSK9 inhibitors require subcutaneous (injectable) administration. The two Health Canada and FDA-approved PCSK9 inhibitors are alirocumab and evolocumab, both administered as subcutaneous injections every 2 weeks or monthly 1, 2.
Current PCSK9 Inhibitor Formulations
The available PCSK9 inhibitors are:
- Alirocumab: 75-150 mg subcutaneously every 2 weeks or 300 mg monthly
- Evolocumab: 140 mg subcutaneously every 2 weeks or 420 mg monthly
- Inclisiran (siRNA): Subcutaneous injection twice yearly (after initial loading doses)
These injectable formulations achieve 50-70% LDL-C reduction and have demonstrated cardiovascular risk reduction in major outcome trials (FOURIER and ODYSSEY Outcomes) 1, 2, 3.
Emerging Oral PCSK9 Inhibitors (Not Yet Approved)
While no oral PCSK9 inhibitor is currently approved, several are in advanced clinical development and show promising results:
Enlicitide (MK-0616)
- Most advanced oral PCSK9 inhibitor in development
- Phase 3 trials (CORALreef-Lipids and CORALreef-HeFH) demonstrate 55-60% LDL-C reduction 4, 5, 6, 7, 8
- Efficacy comparable to injectable PCSK9 inhibitors
- Well-tolerated with safety profile similar to placebo
- Doses ranging from 6-30 mg once daily, with higher doses showing greater efficacy
Other Oral Agents in Development
- Laroprovstat (AZD0780): Up to 50% LDL-C reduction 6
- NNC0385-0434: Development currently suspended despite showing efficacy 6
- DC371739: Dual PCSK9/ANGPTL3 inhibitor 6
Meta-Analysis Evidence
Recent meta-analyses of oral PCSK9 inhibitors (primarily Phase 2-3 trials) show 4, 5, 9:
- LDL-C reduction: 47-60% versus placebo
- ApoB reduction: 38-50%
- Lipoprotein(a) reduction: 19-23%
- Safety: No increased serious adverse events compared to placebo
Clinical Implications
For current practice:
- Patients requiring PCSK9 inhibition must use injectable formulations
- Injectable PCSK9 inhibitors have proven cardiovascular benefit with 15% relative risk reduction in major cardiovascular events 1, 2
- Consider PCSK9 inhibitors for patients with ASCVD or familial hypercholesterolemia who remain above LDL-C targets (≥1.8 mmol/L) despite maximally tolerated statin ± ezetimibe 2, 10
Important caveats:
- The need for injections may limit long-term adherence in some patients
- Cost remains a significant barrier to PCSK9 inhibitor use
- Oral formulations, when approved, may improve adherence and accessibility 4, 11
Future outlook: Oral PCSK9 inhibitors are likely to become available within the next 1-2 years based on ongoing Phase 3 trials. However, cardiovascular outcome data (not just lipid-lowering efficacy) will be needed to establish their role equivalent to current injectable agents 4, 5, 6.