The announcement from Syntara regarding SNT-5505 provides interim data suggesting clinical and commercial differentiation from currently marketed treatments for myelofibrosis (MF).
Here's how it compares:1. Key Competitor Landscape
Drug Developer Primary Use Notes 1 Ruxolitinib (Jakafi) Incyte / Novartis 1st-line JAK1/2 inhibitor; standard of care 2 Fedratinib (Inrebic) BMS 2nd-line JAK2 inhibitor; used post-RUX failure 3 Momelotinib GSK 1st/2nd-line JAK1/2 + ACVR1 inhibitor; addresses anaemia 4 Pacritinib CTI BioPharma / SOBI 2nd-line For patients with thrombocytopaenia 2. Comparative Efficacy – TSS50 (Symptom Reduction)
SNT-5505:
73% (8/11) achieved ≥50% reduction in Total Symptom Score (TSS50)
Mean TSS reduction at Week 52: 63%
Benchmark drugs:
Ruxolitinib (COMFORT-I/II): ~46% achieved TSS50
Momelotinib (MOMENTUM): ~25–28%
Fedratinib (JAKARTA-2): ~26–36% post-RUX
SNT-5505 demonstrates a notably higher symptom reduction rate, particularly in previously RUX-treated patients.
3. Comparative Efficacy – SVR (Spleen Volume Reduction)
SNT-5505:
44% (4/9) achieved SVR25 at 24+ weeks
78% had stable or reduced spleen volume without increasing RUX dose
Benchmark drugs:
Ruxolitinib: ~42–45% SVR35 in first-line
Fedratinib: 32–36% SVR35 post-RUX
Momelotinib: ~25% SVR35 in post-RUX patients
Pacritinib: ~18–29% SVR35 depending on platelet count
Although SVR35 data for SNT-5505 is not yet provided, the SVR25 rates and dose independence from RUX suggest a promising spleen response profile.
4. Safety and Tolerability
Drug Common Adverse Effects 1 Ruxolitinib Anaemia, thrombocytopaenia 2 Fedratinib GI toxicity, risk of Wernicke’s encephalopathy 3 Momelotinib Peripheral neuropathy, diarrhoea 4 Pacritinib GI effects, haematologic toxicity 5 SNT-5505 No treatment-related SAEs; stable blood counts SNT-5505 appears to have a cleaner safety profile, which is especially valuable in a chronic disease context.
5. Positioning and Differentiation
Feature SNT-5505 + RUX Existing JAK inhibitors 1 Mechanism LOX inhibition + JAK JAK-only or JAK+ACVR1 2 Target population RUX suboptimal responders First-line or post-RUX monotherapy 3 Safety Strong Moderate-to-poor in some cohorts 4 Add-on potential High Limited by dose tolerability 5 Durability of response Strong at 52 weeks Most data up to 24–36 weeks SNT-5505 is one of the few therapies showing robust efficacy as an adjunct, making it additive rather than competitive in nature.
Conclusion
SNT-5505 demonstrates:
Superior symptom control in a pre-treated, high-burden population
Stable safety and haematologic profile
Real-world potential as an add-on or second-line agent
If confirmed in a pivotal Phase 3 trial, SNT-5505 could reshape the treatment algorithm by offering a safe, effective adjunct for patients inadequately managed with JAK inhibitors alone.
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The announcement from Syntara regarding SNT-5505 provides...
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