Silence reveals phase 1 data on blood disorder candidate, offering competitive insight

Silence Therapeutics has provided an update on its phase 1 clinical trial for polycythemia vera (PV), revealing early insights into the efficacy of its siRNA candidate, divesiran, in comparison to existing treatments from Incyte and Takeda.

Patients with PV often require regular blood draws, known as phlebotomies, to reduce the number of blood cells and manage blood volume. At the beginning of Silence’s trial, each participant had undergone at least three phlebotomies within the past six months or five within the previous year. Collectively, the trial participants underwent 59 phlebotomies in the six months leading up to the study.

The trial data involved 16 patients, who were divided across three different doses of divesiran. Silence selected participants with varying levels of hematocrit, both above and below the threshold that increases the risk of thrombotic and cardiovascular events. During the follow-up period, which ranged from four to 34 weeks, none of the participants with well-controlled hematocrit levels required a phlebotomy. In contrast, two patients on the middle dose had one blood draw each, all of whom had the highest baseline hematocrit levels.

Silence also tracked changes in hematocrit levels over time within the first two dose cohorts. The data showed a downward trend in hematocrit levels, falling below the risk threshold identified by Silence. However, these cohorts were small, consisting of only 12 patients in total, and the error margins were broad. Furthermore, a more significant change was observed at the higher of the two doses, suggesting a potential dose-response relationship.

Importantly, no patients experienced drug-related serious adverse events, nor did any withdraw due to side effects from divesiran. These findings enable Silence to proceed with the concluding phase of the study, with enrollment expected to be completed by the end of the month. However, uncertainties remain regarding divesiran’s competitiveness in the market.

Incyte’s Jakafi and PharmaEssentia’s Besremi have already secured approval for PV treatment, although both drugs leave room for improvement. Takeda is currently at the forefront of developing a superior PV treatment. Earlier this year, Takeda acquired the rights to Protagonist Therapeutics' phase 3 PV candidate, rusfertide, for $300 million upfront.

Rusfertide is an injectable peptide mimetic of the master iron regulatory hormone, hepcidin. Divesiran, on the other hand, is designed to inhibit the expression of a target involved in hepcidin expression. Despite different mechanisms, both drugs aim to achieve the same objective: increasing hepcidin levels to reduce red blood cell production.