Silence Therapeutics announced it has achieved positive Phase I results with its lead short interfering (si) RNA therapeutic for the treatment of high lipoprotein (Lp)(a), a significant risk factor for cardiovascular disease.
The results are good news for the London-based biotech, which has taken a long time to generate human data. If successful, the company’s candidate drug, currently known as SLN360, will work in a similar way to inclisiran, another lipid-lowering RNA therapeutic developed by competitor Alnylam Pharmaceuticals (now licensed to The Medicines Company, a subsidiary of Novartis).
Alnylam has led the field of RNA silencing therapeutics, achieving the first approval for this type of therapeutic with patisiran in 2018 followed by two others, not including inclisiran.
The cardiovascular disease field is a difficult one to tackle, if potentially lucrative when a drug is successful. High Lp(a) of 50 mg/dl or higher is present in around 20% of people and is a known risk factor for cardiovascular disease.
SLN360 acts to “silence” the LPA gene, which encodes Lp(a), by targeting the transcribed mRNA. In the Phase I study, 32 adults with high Lp(a) but no current cardiovascular disease received injections of the treatment (30 mg, 100 mg, ≤300 mg, or ≤600 mg) or placebo and were then followed up for 150 days.
SLN360 lowered Lp(a) by 46% to 98%, depending on the dose. A reduction of up to 81% was observed at 150 days. No major adverse events were observed, although some low-level injection site reactions were seen at the higher doses. Silence plans to continue to follow up with the participants for 365 days to see if the reductions in Lp(a) continue to be maintained over time.
“These first-in-human data for SLN360, which align with our preclinical findings, reinforce our confidence in its potential to substantially lower Lp(a) levels with long-lasting action and address a major unmet need in cardiovascular disease,” said Giles Campion, head of R&D and chief medical officer at Silence, in a press statement.
“There is currently no specific treatment option approved for high Lp(a), a genetically determined cardiovascular risk factor affecting 20% of the world’s population. Today’s announcement brings us one step closer to addressing a major unmet need in cardiovascular disease,” added CEO Mark Rothera.
While there are available treatments for high cholesterol, such as statins, they don’t work for everyone and the field has been lacking new therapeutics for a while. Inclisiran’s approval by the FDA in December last year for lowering low-density lipoprotein (LDL) cholesterol is the first RNA therapeutic to be approved in this field.
It has the attraction of only needing two injections per year, as opposed to daily pills, an advantage shared by Silence’s candidate therapy. However, the evidence supporting Lp(a)’s contribution to heart disease is arguably less conclusive than that behind LDL cholesterol, high levels of which have long been linked to conditions such as atherosclerosis and other types of cardiovascular disease.
One of the reasons so few cardiovascular drug candidates get to market is the need for very large and expensive late-stage trials to get approval from the regulatory authorities. It is therefore likely Silence will need to partner with a big pharma to reach this stage, should its success with SLN360 continue in Phase II trials that are due to begin towards the end of this year.