BioNTech-Regeneron vs. Moderna-Merck.Cancer Vaccine and PD-1 Inhibitor Combinations.
Introduction
Recent advancements in cancer immunotherapy have seen significant progress with the development of mRNA-based cancer vaccines in combination with PD-1 inhibitors. Two notable combinations are BioNTech-Regeneron's BNT111 with Libtayo (cemiplimab) and Moderna-Merck's mRNA-4157/V940 with Keytruda (pembrolizumab). Both combinations have shown promising results in clinical trials, raising questions about their comparative efficacy.
BioNTech-Regeneron Combination
BioNTech and Regeneron have developed BNT111, an mRNA cancer vaccine, in combination with the PD-1 inhibitor Libtayo (cemiplimab). In a Phase 2 trial involving patients with advanced melanoma, this combination demonstrated a statistically significant improvement in the overall response rate (ORR) compared to historical controls in patients with anti-PD-1 refractory/relapsed melanoma 1 5. The trial's success has positioned this combination as a strong contender in the immunotherapy landscape.
Key Findings:
- Patient Population: Advanced melanoma patients with anti-PD-1 refractory/relapsed disease.
- Efficacy: Statistically significant improvement in ORR.
- Safety: Generally well-tolerated with manageable side effects.
- Regulatory Status: Fast Track and Orphan Drug designations by the FDA 5 6.
Moderna-Merck Combination
Moderna and Merck's investigational personalized mRNA cancer vaccine, mRNA-4157/V940, combined with Keytruda, has also shown promising results. In the Phase 2b KEYNOTE-942 trial, this combination demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence or death compared to Keytruda monotherapy in patients with high-risk stage III/IV melanoma following complete resection 3 4.
Key Findings:
- Patient Population: Stage III/IV melanoma patients with high risk of recurrence.
- Efficacy: 44% reduction in the risk of recurrence or death (HR=0.56) 3 4.
- Safety: Generally safe with a higher rate of serious drug-related side effects compared to Keytruda alone.
- Regulatory Plans: Plans to initiate a Phase 3 study and expand to additional tumor types 3 4.
Comparative Analysis
Both combinations have demonstrated significant efficacy in their respective trials, but there are differences in their patient populations, trial designs, and outcomes that make direct comparisons challenging.
Aspect
BioNTech-Regeneron
Moderna-Merck
Vaccine
BNT111
mRNA-4157/V940
PD-1 Inhibitor
Libtayo (cemiplimab)
Keytruda (pembrolizumab)
Patient Population
Advanced melanoma, anti-PD-1 refractory/relapsed
Stage III/IV melanoma, high risk of recurrence
Efficacy
Significant ORR improvement
44% reduction in recurrence/death risk
Safety
Well-tolerated
Higher rate of serious side effects
Regulatory Status
Fast Track, Orphan Drug designations
Phase 3 study planned
Conclusion
Both BioNTech-Regeneron and Moderna-Merck combinations have shown significant promise in treating melanoma, each with its own strengths. BioNTech-Regeneron's combination has demonstrated efficacy in a particularly challenging patient population, while Moderna-Merck's combination has shown a substantial reduction in recurrence risk. Further comparative studies and Phase 3 trials will be crucial in determining the superior approach for different patient subsets.
References
- BioNTech, Regeneron claim Phase 2 win for cancer vaccine, PD-1 combo.
- BioNTech Announces Positive Topline Phase 2 Results for mRNA Immunotherapy Candidate BNT111 in Patients with Advanced Melanoma.
- Moderna and Merck Announce mRNA-4157/V940, an Investigational Personalized mRNA Cancer Vaccine, in Combination With KEYTRUDA® (pembrolizumab), Met Primary Efficacy Endpoint in Phase 2b KEYNOTE-942 Trial.
- Positive Moderna, Merck cancer vaccine data advances mRNA technology.
Sources:
- (1) BioNTech, Regeneron claim Phase 2 win for cancer vaccine, PD-1 ...
- (2) BioNTech Announces Positive Topline Phase 2 Results for mRNA ...
- (3) Moderna and Merck Announce mRNA-4157/V940, an ...
- (4) Positive Moderna, Merck cancer vaccine data advances mRNA ...
- (5) BioNTech Announces Positive Topline Phase 2 Results for mRNA ...
- (6) BioNTech cancer vaccine hits the spot in melanoma - Pharmaphorum