The Medicines Company’s big gamble on cholesterol-lowering drug inclisiran looks like to could be about to pay off with a US filing later this year.
Top-line data from the phase 3 ORION-11 trial of inclisiran shows that the gene-silencing drug – partnered with Alnylam – hit all its clinical objectives, including a significant reduction in LDL cholesterol from baseline, the primary endpoint.
Inclisiran also hit the mark on secondary endpoints, including the absolute change in LDL cholesterol at various time points between three and 18 months after treatment started, as well as other lipid biomarkers. The results will be presented at the European Society of Cardiology meeting in Paris next week.
The small, interfering RNA (siRNA) drug – which works by blocking the synthesis of PCSK9 in the liver – was being tested in patients with atherosclerotic cardiovascular disease (ASCVD) who were unable to control the LDL-cholesterol levels despite maximum doses of statin drugs, with or without Merck & Co’s add-on therapy Zetia (ezetimibe).
The drugwas given as a subcutaneous injection initially, again at three months and then every six months thereafter. That is a much less frequent dosing regimen than Amgen and Sanofi/Regeneron’s antibody-based PCSK9 inhibitors, inclisiran’s closest competitors, which are given every one to two months.
Analysts suggest that dosing schedule could help inclisiran leapfrog Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab), which have struggled to make headway in the market mainly due to payer resistance.
The companies have had to slash the list prices of their drugs from $14,000 per year at launch to around $6,000 to try to kickstart sales, but are expecting the drugs to gather momentum now that they have cardiovascular outcomes data to go along with surrogate results based on LDL cholesterol.
ORION-11 backs up the safety and efficacy results seen in earlier trials and TMC says it is now planning to submit marketing applications in the US before the end of the year and in Europe in early 2020.
Analyst Umer Raffat of Evercore ISI said safety was the tallest hurdle in front of the programme as it headed into phase 3, and a clean readout from ORION-11 is an important outcome for the entireRNA interference category.
It has two other phase 3 readouts due before then. The ORION-9 trial is testing inclisiran in heterozygous familial hypercholesterolaemia (HeFH), an inherited form of high cholesterol, while ORION-10 is TMC’s confirmatory trial of the drug in ASCVD.
For TMC’s shareholders, the positive top-line data is a massive relief, coming after the company sold off its other assets – including marketed blood thinner Angiomax (bivalirudin) – in order to concentrate on the cholesterol drug.
Shares in the company closed up 14% after the ORION-11 data was announced yesterday and added another couple of points in after-hour trading.