Silence Therapeutics' Divesiran Poised to Disrupt the True Polycythemia Treatment Landscape

Silence Therapeutics' (SLN) divesiran (SLN124) is a Phase 2 siRNA therapy that inhibits TMPRSS6 expression, thereby increasing hepcidin. In the SANRECO trial, the response rate of maintaining hematocrit below 45% without blood draws was 88% in the divesiran group and 19% in the placebo group, with a placebo-adjusted difference of 69 percentage points and a p-value of less than 0.0001. The 6-week or 12-week interval administration has demonstrated, through clinical data, the potential to reduce the burden of frequent blood draws and standard-of-care treatments centered on hydroxyurea, interferon, and ruxolitinib. Following the announcement of these results, Silence Therapeutics finalized a $175 million underwritten offering at $13.50 per ADS, securing funding for subsequent clinical trials and commercialization preparations.

Takeda's Rusfertide Intensifies Competition

Rusfertide, a direct competitor, is an injectable peptide that mimics hepcidin. It is being developed by Protagonist Therapeutics (PTGX), with Takeda Pharmaceutical (TAK) leading the regulatory efforts. The FDA accepted the NDA for rusfertide, based on Phase 3 VERIFY data, on March 2, 2026, and granted it priority review, with a target action date of August 2026. While divesiran's Phase 2 efficacy is promising, rusfertide is ahead in the approval process. Silence Therapeutics still needs to complete a registrational clinical trial and demonstrate long-term safety. In the approximately $4.2 billion true polycythemia treatment market, dosing interval, reduction in blood draws, and the risk of anemia will be key differentiators.

ITM and AbCellera Present Contrasting Clinical and Regulatory Outcomes on the Same Day

ITM Isotope Technologies Munich, a privately held company, received a Complete Response Letter (CRL) from the FDA for ITM-11, also known as lutetium-177 edotreotide, a Phase 3 radioligand therapy targeting SSTR2. The CRL cited issues with the third-party commercial manufacturing facility and manufacturing controls, rather than clinical efficacy or safety data, delaying approval beyond the previously anticipated action date of August 28, 2026. The current standard of care is Lutathera (lutetium Lu 177 dotatate) from Novartis (NVS), which was approved by the FDA on January 26, 2018, and generates annual sales of $816 million. In contrast, AbCellera Biologics' (ABCL) ABCL635, an antibody targeting NK3R, demonstrated a reduction in vasomotor symptoms of 83% in a Phase 2 trial, compared to 33% in the placebo group, and offers the advantage of a single subcutaneous injection.

BioMarin's Decision to Discontinue BMN 401 Highlights Acquisition Risks

BioMarin Pharmaceutical (BMRN) decided to discontinue the development of BMN 401 and INZ-701, subcutaneous injections in Phase 3 trials that supplement the ENPP1 enzyme. While plasma pyrophosphate (PPi) levels increased significantly in the ENERGY 3 trial, the RGI-C co-primary endpoint, which assessed the severity of mucopolysaccharidosis, did not improve, indicating that the biochemical effect did not translate into clinical benefit. BioMarin acquired Inozyme Pharma (INZY) for $4 per share, totaling $270 million in cash, in July 2025, to gain access to this asset. The discontinuation highlights that, even in late-stage asset acquisitions, the selection of endpoints and understanding of disease natural history are critical for realizing the value of the transaction.