The first and only small interfering RNA (siRNA) therapy to lower LDL-cholesterol, inclisiran, has been listed on the PBS as a treatment for some types of hypercholesterolaemia.
Marketed as Leqvio by Novartis Australia, inclisiran is listed from 1 April 2024 for the treatment of patients with heterozygous familial hypercholesterolaemia (HeFH) and non-familial hypercholesterolaemia (non-FH) with atherosclerotic cardiovascular disease (ASCVD), who have additional cardiovascular risk factors, and who are unable to achieve target lipid thresholds with statins, if tolerated, and ezetimibe.
The listing was recommended by the PBAC at its May 2023 meeting (link here) for inclisiran to be subsidised as an alternative to PCSK9 inhibitor therapies such as evolocumab and alirocumabin in the third line setting.
The novel therapy operates as a ‘gene silencer’, inhibiting the translation of PCSK9 in the liver cell, which prevents the degradation of the LDL receptor on the cell surface, leading to a reduction of LDL cholesterol.
The drug is administered as a subcutaneous injection every six months after an initial dose and one at three months.
In a media release from Novartis, Dr Karam Kostner, Associate Professor of Medicine at the University of Queensland and Director of Cardiology at Mater Hospital, Brisbane described the listing as “a fantastic and welcome development in an area of high unmet need.
“The availability of a first-of-its-kind siRNA therapy that only requires twice-yearly dosing provides patients with another highly effective treatment option to help them control their LDL-C levels.
In its decision summary, the PBAC stated that it considered the clinical effectiveness of inclisiran was comparable to evolocumab, although non-inferiority could not be confirmed.
Submissions made by clinicians in support of the listing highlighted the unmet need for new LDL-C lowering therapies to treat patients with hypercholesterolaemia who remained sub-optimally controlled on currently available treatments. There are also patients who are intolerant to statins and PCSK9 inhibitor therapies who would benefit from an alternative therapy option, the PBAC heard.
“The clinician also described the durability of the LDL-C lowering treatment effect associated with inclisiran and the benefits associated with the 6-monthly dosing schedule which included improved adherence to therapy and the better management of patients, particularly those in rural and remote areas and older patients,” the summary noted.