Comparative Value of SNT-5505 vs Marketed MF Drugs

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.