73% of Patients Achieve Major Symptom Improvement with Amsulostat at 24 Weeks
Syntara Limited has reported encouraging Phase 2a results for amsulostat combined with ruxolitinib in treating myelofibrosis, demonstrating sustained symptom improvement and spleen volume reduction over 52 weeks.
- Phase 2a trial of amsulostat plus ruxolitinib completed with 7 patients reaching 52 weeks
- 73% of patients achieved at least 50% symptom score reduction at 24 weeks or beyond
- 44% of evaluable patients showed meaningful spleen volume reduction at 24 weeks
- No treatment-related serious adverse events reported, confirming good safety profile
- Strategic advisory appointments announced to support next clinical development phase
Context and Patient Profile
Syntara Limited (ASX – SNT), a clinical-stage biotech focused on novel therapies for blood cancers, has unveiled top-line data from its Phase 2a trial of amsulostat combined with ruxolitinib (RUX) for myelofibrosis (MF). This open-label study enrolled 16 patients with intermediate-2 or high-risk MF who had been on RUX for an average of three years but continued to experience significant symptoms and enlarged spleens, indicating a high disease burden.
Efficacy and Safety Outcomes
The trial’s key highlight is the sustained clinical benefit observed over 52 weeks. Among patients reaching 24 weeks or beyond, 73% achieved a 50% or greater reduction in total symptom score (TSS50), with some patients reporting complete symptom resolution by the one-year mark. Additionally, 44% of evaluable patients experienced meaningful spleen volume reductions (SVR25) at 24 weeks, with some maintaining these improvements through 52 weeks.
Importantly, amsulostat demonstrated a favourable safety and tolerability profile when combined with RUX, with no treatment-related serious adverse events reported. Haematological parameters such as haemoglobin and platelet counts remained generally stable, and some patients even showed minor improvements in anaemia.
Mechanistic Insights and Scientific Significance
The study also explored amsulostat’s mechanism of action, revealing approximately 90% inhibition of lysyl oxidases (LOX), enzymes implicated in bone marrow fibrosis and disease progression. This LOX inhibition may complement the effects of JAK inhibitors like RUX by targeting fibrosis and growth factor signalling pathways that contribute to treatment resistance. While total collagen content in bone marrow did not significantly decrease, this may be due to RUX’s influence on collagen clearance rather than a lack of anti-fibrotic activity from amsulostat.
Strategic Outlook and Next Steps
CEO Gary Phillips emphasised the competitive and differentiated profile of amsulostat in a challenging patient population, highlighting the drug’s potential to address unmet needs in MF treatment. The company has also announced new strategic, clinical, and commercial advisory appointments to support upcoming clinical development phases and partnership discussions. These results set the stage for regulatory engagement and further trials to refine patient selection and treatment duration.
Overall, Syntara’s Phase 2a data reinforce amsulostat’s promise as a novel adjunct therapy in MF, combining robust symptom relief with a strong safety profile. The company’s next moves will be closely watched by investors and clinicians alike, as they could reshape therapeutic options for this difficult-to-treat disease.
Bottom Line?
Syntara’s promising Phase 2a results position amsulostat as a potential game-changer in myelofibrosis treatment, with pivotal trials and partnerships on the horizon.
Questions in the middle?
- Will larger, controlled trials confirm amsulostat’s efficacy and safety profile?
- How will regulatory agencies respond to these Phase 2a findings in terms of approval pathways?
- What partnership or licensing deals might Syntara pursue to accelerate commercialisation?
