Drugs Xagena
The European Commission ( EC ) has approved Leqvio ( Inclisiran ) for the treatment of adults with hypercholesterolemia or mixed dyslipidemia.
This approval is based on the results of the ORION clinical development program, where Leqvio has provided an effective and sustained low-density lipoprotein cholesterol ( LDL-C ) reduction of up to 52% in patients with elevated LDL-C, despite maximally tolerated statin therapy.
With two doses a year, after an initial dose and one at 3 months, Leqvio is expected to support long-term adherence.
Leqvio is a first-in-class small interfering RNA ( siRNA ) providing effective and sustained LDL cholesterol reduction for patients with atherosclerotic cardiovascular disease ( ASCVD ), ASCVD risk equivalent and heterozygous familial hypercholesterolemia ( HeFH ), which are major drivers of heart attacks, strokes and may ultimately lead to death.
Leqvio is approved for the treatment of adults with primary hypercholesterolemia ( heterozygous familial and non-familial ) or mixed dyslipidemia, as an adjunct to diet: 1)
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 2) alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
ORION-9 was a pivotal phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Inclisiran sodium salt 300 mg, equivalent to 284 mg of Inclisiran, administered subcutaneously by a healthcare professional.
Starting with an initial dose, Inclisiran was then administered again at 3 months and then every 6 months thereafter in 482 participants with clinical or genetic evidence of heterozygous familial hypercholesterolemia ( HeFH ) and elevated low-density lipoprotein cholesterol, despite a maximally tolerated dose of LDL-C-lowering therapies ( e.g. a statin or Ezetimibe ).
For the primary endpoints of ORION-9, Inclisiran delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% ( P less than 0.0001 ) at 17 months and demonstrated time-adjusted percentage change in LDL-C reductions of 44% ( P less than 0.0001 ) from 3 through 18 months.
The international study was conducted at 46 sites in eight countries.
ORION-10 was a pivotal phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Inclisiran sodium salt 300 mg, equivalent to 284 mg of Inclisiran, administered subcutaneously by a healthcare professional.
Starting with an initial dose, Inclisiran was then administered again at 3 months and then every 6 months thereafter in 1,561 participants with atherosclerotic cardiovascular disease ( ASCVD ) and elevated LDL-C, despite a maximally tolerated dose of LDL-C-lowering therapies ( e.g. a statin and/or Ezetimibe ).
For the primary endpoints of ORION-10, Inclisiran has delivered mean placebo-adjusted percentage change in LDL-C reductions of 52% ( P less than 0.0001 ) at 17 months and has demonstrated time-adjusted percentage change in LDL-C reductions of 54% ( P less than 0.0001 ) from 3 through 18 months.
The study was conducted at 145 sites in the United States.
ORION-11 was a pivotal phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Inclisiran sodium salt 300 mg, equivalent to 284 mg of Inclisiran, administered subcutaneously by a healthcare professional.
Starting with an initial dose, Inclisiran was then administered again at 3 months and then every 6 months thereafter in 1,617 patients with ASCVD or ASCVD-risk equivalents and elevated LDL-C despite a maximally tolerated dose of statin therapy ( with or without Ezetimibe ).
For the primary endpoints of ORION-11, Inclisiran delivered placebo-adjusted change in LDL-C reductions of 50% ( P less than 0.0001 ) at 17 months and has demonstrated time-adjusted LDL-C reductions of 49% ( P less than 0.0001 ) from 3 through 18 months.
The international study was conducted at 70 sites in seven countries.
In the phase III trials, Inclisiran was well-tolerated. The most common adverse events reported ( 3% or more of patients treated with Inclisiran and occurring more frequently than placebo ) were injection site reaction, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in extremity and dyspnea.
Among those, injection site reactions were the most frequent ones. Those were generally mild and none were severe or persistent.
Atherosclerosis corresponds to the accumulation of lipids over time mainly low-density lipoprotein cholesterol in the inner lining of the arteries.
Unexpected rupture of the atherosclerotic plaque can cause an atherosclerotic cardiovascular event such as a myocardial infarction or stroke.
ASCVD accounts for over 85% of all cardiovascular disease deaths. ASCVD is the primary cause of death in the European Union and its burden in the United States is greater than that from any other chronic diseases. ( Xagena )
Source: Novartis, 2020
XagenaMedicine_2020
