Sanofi, an integrated global healthcare leader, and Regeneron Pharmaceuticals, Inc., a leading science-based biopharmaceutical company, announced that the US Food and Drug Administration (FDA) approved Praluent (alirocumab) injection, the first FDA-approved treatment in a new class of drugs known as PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors.
Praluent 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 Praluent on cardiovascular morbidity and mortality has not been determined.
Praluent is the first and only PCSK9 inhibitor approved in the US and is available in two different doses (75 mg and 150 mg). Both doses of Praluent 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.
"For patients with high LDL, or bad, cholesterol the primary focus of treatment is to lower their levels, but many patients today do not achieve recommended levels despite lifestyle modifications and treatment with statins," 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 programme.
"In the ODYSSEY clinical trial programme, two doses of alirocumab showed significant LDL cholesterol lowering in a variety of patients who were not able to adequately lower their LDL cholesterol 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."
Many patients in the US face the challenge of achieving LDL cholesterol levels recommended by healthcare providers, despite treatment with standard of care including statins. These include approximately 8-10 million patients with an inherited form of high LDL cholesterol known as heterozygous familial hypercholesterolemia and those with clinical ASCVD, defined as a build-up of plaque in the arteries which can lead to reduced blood flow and a number of conditions including heart attack, stroke, chest pain (stable or unstable angina), transient ischemic attack, revascularization and peripheral artery disease.
"Despite significant progress over the last decades, high cholesterol remains a leading concern in the U.S. and globally," said Olivier Brandicourt, M.D., chief executive officer, Sanofi.
"Praluent demonstrates the power of the Sanofi and Regeneron alliance to deliver a first-in-class therapy in the US for patients in need. Sanofi has a strong cardiovascular heritage and dedication to these patients, and we look forward to working with other regulatory authorities to make Praluent available to patients worldwide."
"We are grateful to the thousands of patients and investigators worldwide who participated in the ODYSSEY clinical trial program," said Leonard S. Schleifer, M.D., Ph.D., founder, president, and chief executive officer, Regeneron.
"Praluent represents the culmination of more than a decade of tireless work to translate the genetic-based discovery of PCSK9 into an innovative medicine that brings meaningful value to patients."
The approval of Praluent was based on data from the pivotal phase 3 ODYSSEY programme, which showed consistent, positive results compared to placebo and included current standard of care therapy (statins). In the ODYSSEY LONG TERM trial which evaluated Praluent 150 mg every two weeks, Praluent reduced LDL cholesterol by 58 per cent versus placebo at week 24 when added to current standard of care, including maximally tolerated statins. In ODYSSEY COMBO I, Praluent 75 mg every two weeks as an adjunct to statins reduced LDL cholesterol by an additional 45 per cent compared to placebo at week 12. At week 24 in the same trial, Praluent reduced LDL cholesterol by an additional 44 per cent compared to placebo. In this study, if additional LDL cholesterol lowering was required based on pre-specified criteria at week 8, Praluent was up-titrated to 150 mg at week 12 for the remainder of the trial. Eighty-three per cent of patients remained on their initial 75 mg dose.
Praluent is generally well-tolerated with an acceptable safety profile. Local injection site reactions including redness, itching, swelling, or pain/tenderness, where the injection is given were the most common events (7.2 per cent with Praluent vs. 5.1 per cent with placebo) and resulted in a low discontinuation rate that was comparable to placebo (0.2 per cent with Praluent vs. 0.4 per cent with placebo). Patients receiving Praluent 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 Praluent than placebo included symptoms of the common cold and flu or flu-like symptoms.
The ODYSSEY phase 3 programme is one of the most comprehensive clinical trial programs ever conducted for an investigational LDL cholesterol lowering therapy. The programme includes 14 global phase 3 trials evaluating more than 23,500 patients. The primary efficacy end point in all of the studies was the mean percent reduction from baseline in LDL cholesterol at week 24 compared to placebo (maximally tolerated statin therapy); all of the completed studies met their primary endpoint. A significantly higher proportion of patients achieved an LDL cholesterol of less than 70 mg/dL in the Praluent group as compared to placebo at both week 12 and week 24. The ongoing ODYSSEY OUTCOMES trial will prospectively evaluate the cardiovascular benefits of Praluent in approximately 18,000 patients.