Silence Therapeutics and the High-Potential Divesiran PV Program: Assessing the Investment Case for a First-in-Class siRNA Therapy in a High-Unmet-Need Hematologic Disorder

The global landscape of hematologic disorders is witnessing a paradigm shift, driven by advancements in RNA therapeutics and precision medicine. Among the most promising candidates is Divesiran, Silence Therapeutics' first-in-class siRNA therapy targeting TMPRSS6 for the treatment of polycythemia vera (PV), a rare, chronic blood cancer characterized by excessive red blood cell production. With the SANRECO Phase 2 trial nearing topline results in Q3 2026, investors are scrutinizing the program's potential to address a high-unmet-need market while navigating a competitive therapeutic landscape.

Divesiran: A Novel Mechanism for a Persistent Challenge

PV affects approximately 20–30 per 100,000 individuals, with current standard-of-care therapies-such as hydroxyurea, interferons, and phlebotomies-often falling short in managing disease burden or tolerability. Divesiran's siRNA mechanism offers a disruptive alternative by silencing TMPRSS6, a key regulator of hepcidin, which in turn modulates iron metabolism and erythropoiesis. This approach aims to reduce the need for phlebotomies and mitigate complications like thrombosis, a leading cause of morbidity in PV patients.

Silence Therapeutics has made significant strides in advancing Divesiran. The SANRECO Phase 2 trial, a global, randomized, double-blind, placebo-controlled study, has completed enrollment of 48 phlebotomy-dependent PV patients, with two dosing regimens (Q6W and Q12W) under evaluation according to biospace. The primary endpoint-proportion of patients maintaining hematocrit (HCT) levels below 45% without phlebotomies between weeks 18 and 36-positions the trial to demonstrate both efficacy and durability according to biospace. Craig Tooman, CEO of Silence, emphasized that the rapid enrollment underscores the company's operational execution and the urgency of addressing PV's unmet needs according to Morningstar.

Market Dynamics: Growth, Competition, and Unmet Needs

The PV treatment market is projected to expand substantially, driven by innovation and a shift toward targeted therapies. According to a report by ResearchNester, the global PV treatment market was valued at USD 8 billion in 2025 and is expected to reach USD 14.8 billion by 2035, with a CAGR of 7.1% according to ResearchNester. In the U.S. alone, the market is anticipated to grow at a faster rate (11.14% CAGR), reaching USD 21.62 billion by 2033 according to LinkedIn. This growth is fueled by advancements in diagnostics, such as JAK2 mutation testing, and the adoption of cytoreductive therapies like hydroxyurea, which dominate 68.7% of the global market by 2035 according to ResearchNester.

However, the competitive landscape is intensifying. Major players like Novartis AG, Bristol-Myers Squibb, and Incyte Corporation are leveraging JAK inhibitors (e.g., Jakafi/Ruxolitinib) to address PV-related myelofibrosis and splenomegaly according to ResearchNester. Emerging therapies, including Givinostat and PTG300, are also entering the fray, offering improved efficacy and reduced side effects according to Biospace. Despite this, Divesiran's siRNA platform presents a unique value proposition: its potential for long-term disease control with infrequent dosing (Q6W/Q12W) could differentiate it in a market where patient adherence and quality of life remain critical challenges.

Investment Risks and Opportunities

While Divesiran's mechanism and trial design are compelling, investors must weigh several risks. First, the SANRECO trial's topline results, expected in Q3 2026, will be pivotal in validating the therapy's efficacy and safety profile. Failure to meet primary endpoints could delay regulatory submissions or necessitate additional studies. Second, the high cost of RNA therapeutics-a class known for complex manufacturing-may limit commercial scalability unless Silence secures strategic partnerships or favorable pricing. Third, the emergence of JAK inhibitors and cytoreductive therapies could erode Divesiran's market share if competitors achieve broader label approvals or demonstrate superior outcomes in high-risk PV populations.

Conversely, the investment case is bolstered by the high unmet need in PV. Current therapies often fail to address iron overload or reduce phlebotomy frequency, leaving a therapeutic gap that Divesiran is uniquely positioned to fill. If the SANRECO trial meets its endpoints, regulatory pathways-such as FDA Breakthrough Therapy Designation-could accelerate approval timelines. Furthermore, the expanding PV market offers a lucrative commercial opportunity, with North America projected to dominate 48.1% of the global market by 2035 due to advanced healthcare infrastructure according to ResearchNester.

Conclusion: A High-Stakes Bet on RNA Innovation

Silence Therapeutics' Divesiran program represents a high-risk, high-reward investment in the evolving PV treatment paradigm. The completion of the SANRECO trial enrollment and the anticipated topline results in Q3 2026 are critical milestones that will shape the therapy's regulatory and commercial trajectory. While the competitive landscape is robust, Divesiran's first-in-class siRNA mechanism and potential for durable disease control could carve out a niche in a market poised for growth. For investors, the key will be monitoring trial outcomes, regulatory developments, and the broader adoption of RNA-based therapies in hematologic disorders.