Merck KGaA will purchase Silence Therapeutics for $1.1 billion, a transaction that includes a drug ready for Phase 3 trials and could differentiate itself within the nascent group of novel treatments currently being developed for a rare blood cancer that has very few available therapeutic choices.
A rare disease focus
Merck KGaA announced an acquisition agreement on Monday to buy all outstanding shares of Silence Therapeutics in a cash deal, aligning with its strategy to expand its pipeline with late-stage or commercialized assets for rare diseases, including Silence’s lead product.
Polycythemia vera, the condition divesiran is intended to treat, is characterized by an overproduction of red blood cells in the bone marrow, leading to thickened blood and increased risk of cardiovascular issues, which can progress to more severe blood cancers like myelofibrosis and acute myeloid leukemia over time.
Silence Therapeutics, based in London, focuses on developing siRNA therapies that target the root cause of diseases by degrading specific messenger RNA, thereby preventing the production of harmful proteins, with the goal of reducing red blood cell levels in patients with polycythemia vera.
Red blood cell levels are regulated by a hormone called hepcidin. Divesiran is an siRNA designed to silence the TMPRSS6 gene, which codes for a liver protein that acts as a brake on hepcidin. Silencing TMPRSS6 is intended to lead to increased production and release of hepcidin by liver cells.
By increasing hepcidin levels, divesiran effectively reduces the amount of iron available for the bone marrow to produce red blood cells, thereby addressing the underlying cause of polycythemia vera and potentially lowering the risk of associated cardiovascular complications.
Phase 2 results
In August, Silence reported Phase 2 results showing divesiran (formerly known as SLN124) led to an 88% response rate compared to 19% for the placebo arm. A response was defined as the absence of phlebotomy as well as hematocrit levels — the percentage of blood volume comprised of red blood cells — below 45%. Hematocrit above that mark is associated with higher rates of death from cardiovascular complications.
The study evaluated six- and 12-week dosing for the injectable drug. Based on these results, Silence said it would test every 12-week dosing in a Phase 3 study planned to begin in the first half of 2027. This dosing schedule would be an advantage over weekly injections of Mimrylo, a Takeda Pharmaceutical drug approved in late August for polycythemia vera.
Mimrylo is a peptide engineered to stand in for hepcidin. PharmaEssentia’s Besremi is given by injection every two weeks. Approved by the FDA in 2021, this polycythemia vera drug is an engineered version of the signaling protein interferon alpha.
The financial terms of the acquisition agreement call for Merck to pay $20 in cash for each American depositary share of Silence, representing a more than 130% premium to the biotech’s closing stock price on Friday and an 82% premium to the average price in the 30-days leading up to the deal. The $1.1 billion figure is Silence’s equity value.
The deal, approved by the boards of both Merck and Silence, is expected to close in the first quarter of 2027, pending shareholder and regulatory approval, marking another step in Merck’s strategy to bolster its pipeline with innovative therapies for rare diseases.
Merck’s growth strategy is placing particular emphasis on adding rare disease medicines. Last year, the company exercised its option for global commercialization rights to pimicotinib, an Abbisko drug currently under FDA review for treating tenosynovial giant cell tumor, a rare type of tumor that develops in or around joints.
Market positioning
The Takeda and PharmaEssentia drugs may be used in the first-line setting. The second-line setting includes Incyte’s JAK inhibitor Jakafi, which added the indication to its label in 2014.
Strategic expansion
Soon after that deal, Merck agreed to pay $3.9 billion to buy SpringWorks Therapeutics. SpringWorks Therapeutics has two FDA-approved drugs for rare tumors. These drugs are Ogsiveo for desmoid tumors and Gomekli for neurofibromatosis type 1. The Silence acquisition further strengthens this rare disease portfolio.
