Silence Therapeutics Pauses Phase III Development of Zerlasiran, Shifts Focus to Rare Diseases

Silence Therapeutics, a biotechnology company specializing in RNA interference (RNAi) therapies, has announced a strategic shift in its development pipeline, pausing the Phase III trial of its cardiovascular drug zerlasiran while redirecting resources to rare disease treatments.

Zerlasiran Development on Hold Pending Partnership

Silence Therapeutics has decided to halt the initiation of a Phase III cardiovascular outcomes study for zerlasiran, its investigational short interfering RNA (siRNA) therapy targeting lipoprotein(a) [Lp(a)]. The company cites the need for a collaborative partner to proceed with late-stage development.

"While we remain confident in our zerlasiran program for high Lp(a), we will only initiate the Phase 3 cardiovascular outcomes study once a partner is secured," stated CEO Craig Tooman. This decision aligns with the company's financial strategy, as CFO Rhonda Hellums noted, "The decision not to initiate the zerlasiran Phase 3 outcomes study without a partner extends our projected cash runway into 2027."

Despite the pause, Silence has received positive regulatory feedback from the FDA regarding the planned Phase III study. The company reported promising results from earlier trials, with zerlasiran demonstrating a median maximum Lp(a) reduction of approximately 90% at 48 weeks in high-risk patients.

Strategic Pivot to Rare Diseases

As part of its 2025 growth strategy, Silence Therapeutics is refocusing its efforts on rare conditions. CEO Tooman explained, "In 2025, we are prioritizing investment in programs targeting rare conditions where we believe we can deliver on clear unmet needs with first-in-class and/or best-in-class siRNAs."

At the forefront of this new direction is divesiran, a mid-stage asset being developed for polycythemia vera and other hematologic indications. The company has completed the Phase I SANRECO study for divesiran and plans to present the data at upcoming medical conferences. Additionally, Silence expects to fully enroll the Phase II SANRECO study by the end of the year.

Financial Position and Future Outlook

As of the end of 2024, Silence Therapeutics reported a strong financial position with $147.3 million in cash, cash equivalents, and short-term investments. The company's decision to pause zerlasiran's Phase III development is expected to contribute to an extended cash runway, potentially lasting into 2027.

While Silence continues to seek a partner for zerlasiran, the company remains committed to advancing its pipeline of siRNA therapeutics, with a particular emphasis on addressing unmet needs in rare diseases. The coming year will likely see increased focus on divesiran's development and potential expansion into additional hematologic indications.