October 16, 2020:”Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMA has adopted a positive opinion and recommended granting marketing authorization of Leqvio®* (inclisiran) for the treatment of adults with hypercholesterolemia or mixed dyslipidemia, marking an important milestone towards it becoming available in the EU.
Inclisiran is a potential first-in-class small interfering RNA (siRNA) with a new mechanism of action which delivers effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalent and heterozygous familial hypercholesterolemia (HeFH) a major driver of heart attacks, strokes and deaths.
“This investigational medicine could significantly change how high LDL-C is treated,” said Professor Ulf Landmesser, M.D., Director of Charité Center for Cardiovascular Diseases, Berlin.
“Many patients struggle to keep their LDL-C at recommended levels, and long-term exposure to high LDL-C is a major driver of ASCVD.
The unique mechanism of action of inclisiran provides effective and sustained LDL-C reduction, a causal factor of atherosclerotic disease progression.
With only two doses a year, and as an injection administered by healthcare professionals, it is anticipated to remove adherence challenges commonly encountered with self-administered treatments.”
“LDL-C reduction remains a major public health issue, with 80% of high-risk patients in Europe not achieving guideline-recommended LDL-C targets despite available current standard of care treatments.
These patients remain at risk of ASCVD events, such as strokes or heart attacks”, said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis.
“This encouraging positive CHMP opinion is a significant step in our journey of reimagining medicine with this transformational treatment, which has the potential to bring new hope to the millions of people in Europe currently unable to reach their LDL-C goals.”
This CHMP opinion is based on results from the ORION clinical research program including Phase III trials, which involved more than 3,600 patients on a maximally tolerated statin dose and assessed the safety, efficacy and tolerability of inclisiran.
Inclisiran demonstrated effective and sustained LDL-C reduction of up to 52% (P<0.0001) with two doses per year, after an initial dose and one at 3 months, in adults with ASCVD, ASCVD risk equivalent and/or HeFH.
Further, the reduction in LDL-C achieved with inclisiran was sustained through 17 months, with a safety and tolerability profile similar to placebo.
Additional post hoc analysis showed low variability among the patients treated with inclisiran: 88% of them reached guideline recommended targets at any timepoint during the study (observed values).
The CHMP recommended granting inclisiran marketing authorization for the treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet:
- in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximally tolerated dose of a statin, or
- alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
The European Commission (EC) – which has the authority to approve medicines for the European Union (EU) – will review the CHMP opinion and is expected to grant a centralized marketing authorization that will be valid in the 27 countries that are members of the EU.
Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions based on the EC’s recommendation.
Following EC approval, Novartis will continue to explore innovative collaborations with health agencies and others throughout Europe designed to ensure that people with ASCVD and elevated LDL-C have access to the treatments they need to achieve beneficial health outcomes.
Further, Novartis looks forward to the completion of the ongoing cardiovascular outcomes ORION-4 study, which will expand on the scientific evidence associating lower LDL-C levels with improved cardiovascular outcomes.
Inclisiran is also under review by the U.S. Food and Drug Administration for the treatment of primary hyperlipidemia (including HeFH) in adults who have elevated LDL-C while being on a maximally tolerated dose of statin therapy.