Silence Therapeutics announced encouraging results from its ongoing Phase I study of divesiran (SLN124), a potential first-in-class siRNA therapy for patients with polycythaemia vera (PV). The drug, which targets TMPRSS6, aims to increase hepcidin production, thereby restricting iron availability to the bone marrow and reducing the excessive red blood cell production that is characteristic of the disease. "What we see today is a very clear picture," said CEO Craig Tooman on a call with investors. "We are excited about the potential for divesiran to be the first siRNA therapy for PV." He added that a Phase II study start is planned by year-end. The treatment goal for PV is to lower haematocrit (HCT) levels to less than 45% in order to reduce cardiovascular and major thrombotic events. Current standard of care includes repeated phlebotomies to lower HCT and/or cytoreductive agents to reduce red blood cell production.
Near elimination of phlebotomies
Thursday's readout centres on data from 16 patients enrolled in the ongoing SANRECO study. It included three dose cohorts who received divesiran administered subcutaneously every six weeks over the course of the 34-week study. The trial included both well-controlled patients – meaning they had HCT of ≤45% at baseline – as well as those with HCT levels over 45% despite being on current standard therapies. According to Silence, none of the eight well-controlled patients required phlebotomy during the treatment period, and only two out of the other eight patients with baseline HCTs over 45% required one phlebotomy. As a comparison, there were a total of 59 phlebotomies across the 16 patients reported during the six months prior to study entry.
While the company tested a six-week dosing schedule, R&D head Steven Romano noted that "based on the data we're collecting and continue to collect, we do see an opportunity potentially for a less frequent dosing strategy, but that will not be determined until we complete Phase I and move into Phase II."
The company also reported favourable effects on iron metabolism indices across all dose groups, while hepcidin levels increased and remained within physiological ranges, demonstrating effective target engagement. No major safety issues were reported. More detailed results will be shared at a scientific meeting later this year. Meanwhile, the progress of divesiran comes amid increasing interest in novel therapies for PV. Earlier this year, Takeda agreed to pay $300 million upfront as part of a licensing deal with Protagonist Therapeutics for rusfertide, an injectable hepcidin mimetic peptide currently in Phase III testing for PV. The company anticipates topline data from the VERIFY study by the end of the first quarter of 2025. Recent long-term follow-up data from rusfertide's Phase II REVIVE trial showed durable HCT control and decreased phlebotomy for up to three years.