Approval of another PCSK9-inhibitor to treat hypercholesterolaemia
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News - July 27, 2015The U.S. Food and Drug Administration (FDA) approved alirocumab injection, the first FDA-approved treatment in a new class of drugs known as PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low-density lipoprotein (LDL) cholesterol. The effect of alirocumab on cardiovascular morbidity and mortality has not been determined.
Alirocumab is available in two different doses (75 mg and 150 mg). Both doses of alirocumab are available in a single 1 milliliter (mL) injection delivered in a single-dose prefilled pen or syringe that patients self-administer every two weeks.
The approval of alirocumab was based on data from the pivotal Phase 3 ODYSSEY program, which showed consistent, positive results compared to placebo and included current standard of care therapy (statins). In the ODYSSEY LONG TERM trial that evaluated alirocumab 150 mg every two weeks, alirocumab reduced LDL-c by 58% versus placebo at week 24 when added to current standard of care, including maximally tolerated statins. In ODYSSEY COMBO I, alirocumab 75 mg every two weeks as an adjunct to statins reduced LDL-c by an additional 45% compared to placebo at week 12. At week 24 in the same trial, alirocumab reduced LDL-c by an additional 44% compared to placebo. In this study, if additional LDL-c lowering was required based on pre-specified criteria at week 8, alirocumab was up-titrated to 150 mg at week 12 for the remainder of the trial. 83% of patients remained on their initial 75 mg dose.
"In the ODYSSEY clinical trial program, two doses of alirocumab showed significant LDL-c lowering in a variety of patients who were not able to adequately lower their LDL-c with current standard of care alone. The majority of patients achieved their LDL-lowering goals with the 75 mg dose, when added to maximally tolerated dose of a statin, with a generally acceptable safety profile," said Christopher Cannon, M.D., Professor of Medicine at Harvard Medical School, Cardiovascular Division at Brigham and Women's Hospital, and a member of the Steering Committee for the Phase 3 ODYSSEY clinical trial program.
Alirocumab is generally well-tolerated with an acceptable safety profile. Local injection site reactions including redness, itching, swelling, or pain/tenderness, were the most common events (7.2% with alirocumab vs. 5.1% with placebo) and resulted in a low discontinuation rate that was comparable to placebo (0.2 % with alirocumab vs. 0.4% with placebo). Patients receiving alirocumab had a greater number of injection site reactions, had more reports of associated symptoms, and had reactions of longer average duration than patients receiving placebo. Other common adverse events occurring more frequently in patients with alirocumab than placebo included symptoms of the common cold and flu or flu-like symptoms.
Europe
The European Medicine Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorisation of alirocumab, recommending its approval for use in in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:
Press release Sanofi July 24 20105 – EMA recommendation
Press release EMA July 24 2015
Alirocumab is available in two different doses (75 mg and 150 mg). Both doses of alirocumab are available in a single 1 milliliter (mL) injection delivered in a single-dose prefilled pen or syringe that patients self-administer every two weeks.
The approval of alirocumab was based on data from the pivotal Phase 3 ODYSSEY program, which showed consistent, positive results compared to placebo and included current standard of care therapy (statins). In the ODYSSEY LONG TERM trial that evaluated alirocumab 150 mg every two weeks, alirocumab reduced LDL-c by 58% versus placebo at week 24 when added to current standard of care, including maximally tolerated statins. In ODYSSEY COMBO I, alirocumab 75 mg every two weeks as an adjunct to statins reduced LDL-c by an additional 45% compared to placebo at week 12. At week 24 in the same trial, alirocumab reduced LDL-c by an additional 44% compared to placebo. In this study, if additional LDL-c lowering was required based on pre-specified criteria at week 8, alirocumab was up-titrated to 150 mg at week 12 for the remainder of the trial. 83% of patients remained on their initial 75 mg dose.
"In the ODYSSEY clinical trial program, two doses of alirocumab showed significant LDL-c lowering in a variety of patients who were not able to adequately lower their LDL-c with current standard of care alone. The majority of patients achieved their LDL-lowering goals with the 75 mg dose, when added to maximally tolerated dose of a statin, with a generally acceptable safety profile," said Christopher Cannon, M.D., Professor of Medicine at Harvard Medical School, Cardiovascular Division at Brigham and Women's Hospital, and a member of the Steering Committee for the Phase 3 ODYSSEY clinical trial program.
Alirocumab is generally well-tolerated with an acceptable safety profile. Local injection site reactions including redness, itching, swelling, or pain/tenderness, were the most common events (7.2% with alirocumab vs. 5.1% with placebo) and resulted in a low discontinuation rate that was comparable to placebo (0.2 % with alirocumab vs. 0.4% with placebo). Patients receiving alirocumab had a greater number of injection site reactions, had more reports of associated symptoms, and had reactions of longer average duration than patients receiving placebo. Other common adverse events occurring more frequently in patients with alirocumab than placebo included symptoms of the common cold and flu or flu-like symptoms.
Europe
The European Medicine Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorisation of alirocumab, recommending its approval for use in in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, 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 maximum 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 CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation (final decision expected in September 2015). Once a marketing authorisation has been granted, each Member State will take a decision on price and reimbursement based on the potential role/use of this medicine in the context of its national health system.
Press release Sanofi July 24 20105 – EMA recommendation
Press release EMA July 24 2015
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