Merck KGaA is acquiring Silence Therapeutics in a $1.1 billion deal that comes with a Phase 3-ready drug offering the potential to stand out in an emerging class of new therapies in development for a rare type of blood cancer with limited treatment options.
The acquisition agreement announced Monday calls for Darmstadt, Germany-based Merck KGaA to acquire the outstanding shares of Silence in an all-cash transaction. Silence’s lead asset fits within Merck’s pipeline growth strategy of adding commercialized or late-clinical assets in rare diseases.
The Silence drug, divesiran, is in development for polycythemia vera, a rare blood cancer in which the bone marrow produces too many red blood cells, which results in thicker blood that raises the risk of cardiovascular complications. Over time, this chronic condition can lead to the blood cancers myelofibrosis and acute myeloid leukemia. The main treatment for polycythemia vera is therapeutic phlebotomy, periodic removal of blood to lower the red blood cell count.
London-based Silence specializes in developing short or small interfering RNA (siRNA) therapies designed to degrade the messenger RNA carrying instructions for making a protein that drives disease, an approach that is also called gene silencing. Silence aims to treat polycythemia vera by reducing a patient’s levels of red blood cells.
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’s like a brake on hepcidin. Silencing TMPRSS6 is intended to lead to increased production and release of hepcidin by liver cells. Higher hepcidin levels increases the storage of iron in the body, keeping iron from reaching the bloodstream where it would be available for making more red blood cells.
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 the Phase 2 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 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.
The emerging competition in polycythemia vera aims to address TMPRSS6. Agios Pharmaceuticals has a TMPRSS6-silencing siRNA drug in early clinical development. Disc Medicine is in mid-stage development with an antibody that blocks the protein coded by TMPRSS6. Ono Pharmaceutical’s sapablursen, a TMPRSS6-targeting antisense oligonucleotide, is in late-stage clinical development.
Divesiran’s Phase 2 results persuaded William Blair analyst Myles Minter the Silence drug could be best in the polycythemia vera field. Acknowledging the caveats with cross-trial comparison, he said in a research note that the Silence drug looks good compared to the Disc and Ono drugs. With Takeda projecting Mimrylo reaching up to $2 billion in peak sales in polycythemia vera, Minter said the Silence deal appears inexpensive considering Merck also gains the biotech’s siRNA platform technology.
Merck’s acquisition agreement for Silence is the culmination of a competitive process, Iain Ross, Silence’s interim principal executive officer and chairman of the company’s board of directors, said in a prepared statement. He added that the German company has the scale and resources for the clinical development and potential commercialization of the siRNA therapy.
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. Soon after that deal, Merck agreed to pay $3.9 billion to buy SpringWorks Therapeutics, a company with two FDA-approved drugs for rare tumors, Ogsiveo for desmoid tumors and Gomekli for neurofibromatosis type 1. In a prepared statement, Danny Bar-Zohar, member of the executive board and CEO of healthcare at Merck KGaA, said the Silence’s divesiran offers a strategic fit and best-in-class potential.
“The planned acquisition also provides an entry point into hematology through a biologically validated mechanism of action,” he said. “With this transaction, we are advancing our efforts to build a differentiated, sustainable pipeline as we bring more medicines to more patients, faster.”
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 boards of Merck and Silence have approved the deal, which still requires the sign off of Silence shareholders and regulators. The companies expect to close the transaction in the first quarter of 2027.
Photo: Hannelore Foerster/Bloomberg, via Getty Images
