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TMC’s full data for inclisiran impresses at ESC

Marketing applications expected before end of year


The Medicine’s Company has unveiled the impressive detailed results of its LDL-C lowering drug inclisiran at the ESC 2019, setting up a potential clash with market rivals. 

The drug targets the interfering RNA (siRNA) which blocks the synthesis of PCSK9 in the liver – this allows more receptors on the liver cell surface to capture LDLs for break down. By lowering LDL levels, or ‘bad’ cholesterol, the likelihood of major cardiac events decreases.

Other PCKS9 targeting drugs, including Amgen’s Repatha and Sanofi/Regeneron’s Praluent, directly target the  PCKS9 protein. TMC has maintained that inclisiran is potentially first-in-class, as it targets the siRNA which eventually produces the protein. Inclisiran also has an advantage with its twice-yearly dosing schedule, as its competitors must be administered either every two weeks or once a month.

The data comes from TMC’s ORION-11 phase 3 clinical trial, in patients with ASCVD or ASCVD-risk equivalents, who had elevated LDL-C levels despite being on the maximum dose of statin therapy. The drug achieved its primary endpoint, with a 54% reduction in LDL, with time-adjusted reduction of 50% over 18 months of treatment.

The safety of the drug compared to placebo was also similar, with patients treated with placebo or inclisiran experiencing a similar level of at least one serious treatment emergent adverse event at 22.5% and 22.3% respectively. The instances of deaths (1.9% and 1.7%) and malignancies (2.5% and 2.0%) were also similar between placebo and inclisiran groups.

However, a difference was observed in the incidence of fatal and non-fatal heart attacks, with placebo groups at 2.7% and inclisiran at 1.2%. Fatal and non-fatal strokes incidences were also different with those treated with the drug at 0.2% compared to 1.0% in the placebo group.

Improving cardiovascular outcomes is key to the success of LDL-lowering drugs, and this early data makes the case for the efficacy of inclisiran in this area.

TMC licensed the rights to inclisiran from Alnylam Pharmaceuticals, and the drug still uses Alnylam’s delivery platform. Initial doubts around the potential success of inclisiran centred on this one aspect, as this platform has recently been linked to liver toxicity.

However, following the full data set these doubts have now been alleviated – liver function tests across the placebo and inclisiran groups proved to be similar, with ALT levels in both groups at 0.5% and AST at 0.5% and 0.2% respectively.

On the back of the ORION-11 success, TMC says it is now planning to submit marketing applications for inclisiran in the US before the end of the year and in Europe in early 2020. It also has two other phase 3 readouts due before then – ORION-9 is testing the drug in heterozygous familial hypercholesterolaemia (HeFH) and ORION-10 is conducting a confirmatory trial in ASCVD.

Article by
Lucy Parsons

3rd September 2019

From: Research



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