Silence Therapeutics Halts Zerlasiran Phase 3 Despite 80% Lp(a) Reduction

Silence Therapeutics recently shared an update regarding its zerlasiran program, indicating a shift in its strategy for advancing this treatment for atherosclerotic cardiovascular disease. While phase 2 trial data presented at the American Heart Association (AHA) conference in November had initially set the stage for a phase 3 trial, the company has now clarified that it will not proceed further without securing a partner.
Strategic Shift in the Zerlasiran Program
Zerlasiran is an investigational small interfering RNA (siRNA) therapy designed to target the LPA gene, thereby reducing lipoprotein(a) [Lp(a)] levels. Results from the phase 2 study demonstrated that the therapy achieved an 80% placebo-adjusted reduction in Lp(a) concentrations over a span of 36 weeks. When these findings were initially presented, Silence Therapeutics expressed optimism about their potential in shaping the dosage for a phase 3 trial. However, a more recent update from the company has confirmed that any further progression will be contingent upon the establishment of a strategic partnership.
This decision was reaffirmed by CEO Craig Tooman in the company’s fourth-quarter earnings report. Tooman emphasized that the organization remains confident in the potential of zerlasiran while also acknowledging the necessity of securing external collaboration before proceeding to the next phase of clinical 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,” he stated. Meanwhile, the company continues to engage in discussions with potential collaborators and is ensuring that essential activities are maintained so that the program remains ready for phase 3 trials in the first half of 2025.
Financial factors have played a significant role in determining this strategic adjustment. CFO Rhonda Hellums reported that the company concluded the year with over $147 million in cash, cash equivalents, and short-term investments. By choosing to postpone the phase 3 study until a partnership is secured, Silence Therapeutics is able to extend its projected financial runway into 2027. This approach not only supports financial sustainability but also enables the company to continue making investments in other key programs within its pipeline while ongoing partnership discussions for zerlasiran progress.
Among the other priority programs within Silence Therapeutics’ pipeline is divesiran, another siRNA-based therapy currently in phase 2 trials. This therapy is being evaluated as a potential treatment for polycythemia vera (PV), a rare blood disorder. Tooman has underscored the company’s commitment to developing treatments for rare diseases with significant unmet medical needs, positioning divesiran as a central example of this approach.
Alongside its evolving clinical strategy, Silence Therapeutics must also navigate the absence of potential milestone payments that were previously anticipated through a collaboration with Hansoh Pharma. The partnership, initiated in 2021, initially provided Silence with an upfront payment of $16 million to support the development of therapies using its mRNAi GOLD platform. However, the company has now disclosed that Hansoh has chosen not to proceed with further development, prompting Silence to reassess its approach to advancing these preclinical programs independently.