Silence brings the noise to Takeda with phase 2 blood cancer win

Biotech Silence brings the noise to Takeda with phase 2 blood cancer win By Nick Paul Taylor Aug 10, 2026 7:31am Silence Therapeutics siRNA blood cancer Takeda A phase 2 trial of Silence Therapeutics’ divesiran has hit its primary endpoint, emboldening the biotech to gear up for late-phase development of a potential challenger to Takeda and Protagonist Therapeutics’ rusfertide. The biotech designed divesiran, a siRNA drug candidate, to treat a rare blood cancer characterized by the excessive production of red blood cells. By silencing the production of a protein, TMPRSS6, found in liver cells, Silence hopes to redirect iron delivery away from bone marrow, slow production of red blood cells and improve outcomes in patients with the cancer, polycythemia vera (PV).

To test that idea, the company enrolled 48 patients who depended on blood draws to control their PV. Between Weeks 18 and 36 of the trial, 88% of patients on divesiran met the response criteria, compared to 19% of people on placebo, achieving the primary endpoint. The response rate was 93.8% in people who received divesiran every six weeks and 81.3% in the 12-week dose cohort.

Silence defined a response as the absence of phlebotomy—the medical term for blood draw—and the maintenance of hematocrit (HCT) below 45%. The HCT level is the threshold above which PV patients are eligible for phlebotomy. Takeda and Protagonist have filed for FDA approval of rusfertide in PV based on a phase 3 trial that linked the peptide hepcidin mimetic to a 76.9% response rate from Week 20 to 32.

The placebo response rate was 32.9% in the rusfertide trial. Protagonist’s phase 2 trial used a randomized withdrawal design. In the withdrawal phase, the rusfertide and placebo response rates were 60% and 17%, respectively.

Attracted by the data, Takeda paid Protagonist $300 million upfront for rights to the drug candidate in 2024. The partners expect to receive FDA approval in the third quarter, meaning that rusfertide could be on the market before Silence starts a phase 3 trial in the first half of next year. Silence’s weapons for overcoming rusfertide’s headstart include its dosing regimen.

Rusfertide, which mimics a hormone that regulates iron homeostasis, was given as a weekly, self-administered injection in phase 3. Silence plans to administer divesiran every 12 weeks in its phase 3 trial. The biotech is advancing toward phase 3 armed with a hit on a key secondary endpoint.

The phlebotomy rate on divesiran was 0.2 in the phase 2 clinical trial, compared to 2.1 on placebo. Silence also reported improvements in hematocrit control, iron markers including ferritin and patient reported outcomes. No new safety signals were seen.

Silence ended March with $70.1 million in cash and short-term investments. Silence Therapeutics siRNA blood cancer Takeda Protagonist Therapeutics Clinical Data Biotech