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 |
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| 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:
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:
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 |
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| 2 | Fedratinib | GI toxicity, risk of Wernicke’s encephalopathy |
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| 3 | Momelotinib | Peripheral neuropathy, diarrhoea |
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| 4 | Pacritinib | GI effects, haematologic toxicity |
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| 5 | SNT-5505 | No treatment-related SAEs; stable blood counts |
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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 |
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| 2 | Target population | RUX suboptimal responders | First-line or post-RUX monotherapy |
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| 3 | Safety | Strong | Moderate-to-poor in some cohorts |
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| 4 | Add-on potential | High | Limited by dose tolerability |
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| 5 | Durability of response | Strong at 52 weeks | Most data up to 24–36 weeks |
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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.
