Evolocumab (Repatha), a novel first-in-class treatment to lower cholesterol
Last Updated on May 24, 2015 by Joseph Gut – thasso
May 22, 2015 – The European Medicines Agency (EMA) has recommended authorising Evolocumab (Repatha) as treatment to lower high levels of cholesterol in the blood of people who are unable to control their cholesterol despite taking optimal doses of statins or who cannot take statins. It should be used in addition to a healthy diet. Other lipid-lowering therapies (statins and others) should also be used if tolerated.
Evolocumab (Repatha) is also indicated to treat people with homozygous familial hypercholesterolaemia, a rare inherited disorder in which levels of LDL-cholesterol (‘bad cholesterol’) are higher than normal from birth. It is intended for injection under the skin either once every two weeks, or once a month. High levels of cholesterol in the blood are common risk factors for heart disease, which is the leading cause of death globally.
Repatha is the first monoclonal antibody in this therapeutic area and provides a new treatment option for patients who are unable to control their high cholesterol despite taking currently available therapies. Repatha blocks the PCSK9 protein, which would otherwise lower
the number of LDL-receptors in the liver and through this, diminishes its ability to remove LDL-cholesterol from the blood.
The efficacy of Repatha as a lipid-lowering agent was assessed in nine trials (about 5,500 people) in patients with hypercholesterolaemia and mixed dyslipidaemia, and in two studies (about 250 people) in patients with homozygous familial hypercholesterolaemia. Repatha reduced LDL-cholesterol for both patient groups. Available evidence does not yet allow the longer term benefits of Repatha for patients in reducing heart disease or death from heart disease to be determined.
The Committee for Medicinal Products for Human Use (CHMP) also looked at safety information from patients with hypercholesterolaemia and mixed dyslipidaemia (over 6,000 patients followed for at least six months and over 1,100 patients followed for at least two years). The Committee considered that the safety profile of Repatha is acceptable, with few patients discontinuing treatment or showing serious adverse events. A similar safety profile was observed in patients with homozygous familial hypercholesterolaemia. Further data will be collected to assess the implications of very low cholesterol levels.
The full indication for Repatha approved by the CHMP is as follows:
- Repatha is indicated 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 contra-indicated;
- Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies;
- The effect of Repatha on cardiovascular morbidity and mortality has not yet been determined.
The company received scientific advice on clinical aspects of the application from the CHMP. This is one of the Agency’s main tools to facilitate and stimulate research and development within the European Union (EU).
The opinion adopted by the CHMP at its May 2015 meeting is an intermediary step on Repatha’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. 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.
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Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.
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July 10, 2015 – Further to the first comment, Sanofi announded on June 09, 2015, that FDA Advisory Committee Recommends Approval of Sanofi and Regeneron’s Praluent® (alirocumab) Injection for Patients with Hypercholesterolemia according to the press release below.
PARIS and TARRYTOWN, N.Y., June 9, 2015 /PRNewswire/ — Sanofi and Regeneron Pharmaceuticals, Inc. today announced that the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) of the U.S. Food and Drug Administration (FDA) recommended the approval of the investigational therapy Praluent® (alirocumab) Injection. The Committee voted 13 to 3 (with no abstentions) that Sanofi and Regeneron had sufficiently established that the low-density lipoprotein cholesterol (LDL-C, or bad cholesterol) lowering benefit of Praluent exceeds its risks to support approval in one or more patient populations.
The Committee’s recommendation was based on Praluent’s benefit-risk profile, following review of efficacy and safety data from more than 5,000 patients across 10 pivotal Phase 3 double-blind trials ranging from six months to two years. Clinical data from the ODYSSEY Phase 3 program show consistent, positive results in reducing LDL-C. Common adverse events that were more frequently reported in patients treated with Praluent than the control groups included injection site reaction and pruritus (itching).
“The discovery of PCSK9 as a powerful regulator of cholesterol levels and cardiovascular disease was one of the most important human genetic advances of the last decade,” said George Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President, Regeneron Laboratories. “Today’s outcome brings us one step closer to translating this genetics-based discovery into a treatment that may help the many patients in need of additional cholesterol lowering.”
The Advisory Committee’s recommendation will be considered by the FDA in its review of the Biologics License Application (BLA) for Praluent. The FDA is not bound by the Committee’s recommendation, but takes its advice into consideration when reviewing investigational medicines. The BLA for Praluent was accepted for priority review by the FDA with a target action date of July 24, 2015.
June 07, 2015 – This is a note I just found on Bloomberg Business referring to FDA’ s mulling over Praluent, Sanofi’ entering into new mode of action market of cholesterol-lowering drugs, acting as PCSK9 inhibitors. It seems that with Praluent and the very similar Repatha viable alternatves for some patients are on the not to distant horizon.
Here find the note in its entirety:
The cholesterol-lowering effect of Sanofi and Regeneron Pharmaceuticals Inc.’s Praluent is significant, U.S. regulators said, while questioning whether the companies should have to prove the drugs cut the risk of heart attack and death before they’re used broadly.
High cholesterol is linked to heart disease, the No. 1 killer of Americans, and drugs that lower bad cholesterol are generally assumed to be good for the heart. Yet, Food and Drug Administration staff will ask outside advisers to consider whether, without a proven link between the drugs and lower heart deaths, cutting bad cholesterol levels is enough to approve the drug in certain patients, according to a report released Friday.
The medicine “significantly” lowered LDL, or low-density lipoprotein, cholesterol and was well tolerated by patients, FDA staff wrote.
The report comes ahead of a June 9 meeting of FDA advisers to consider the drug, which falls in a new class of therapies known as PCSK9 inhibitors. Agency advisers will consider another treatment of the same type from Amgen Inc. on June 10.
The possibility that LDL reduction isn’t always a surrogate for decreased risk of heart disease is “particularly relevant” now that statins are the go-to cholesterol treatment and have proven a heart benefit, FDA staff said in the report.
Regeneron shares rose less than 1 percent to $519.07 at 9:34 in New York. Sanofi fell 1.9 percent to 89.41 euros. Amgen gained less than 1 percent to $158.90.
Feasible Endeavor
In addition, FDA staff wrote that trials to measure a drug’s effect on the heart “is no longer considered the infeasible endeavor that it was when our advisory committee last discussed issues related to the pre-approval assessment of lipid-altering drugs approximately 25 years ago.”
Sanofi and Regeneron are seeking to sell Praluent to patients that aren’t able to control their cholesterol on statins alone or can’t tolerate them. The FDA staff also questioned whether calling patients statin intolerant in labeling for Praluent will be misleading and encourage patients to prematurely abandon statins.
Praluent and Amgen’s Repatha cut bad cholesterol levels by more than 60 percent in studies published in March in the New England Journal of Medicine. Both are attempting to show lower cholesterol levels will have a benefit on heart health as well in large clinical trials that will be completed in 2017.
New Class
Praluent, also known as alirocumab, is expected to be the first PCSK9 drug for sale in the U.S. The FDA is scheduled to decide whether to approve it by July 24, followed by a decision on Amgen’s treatment by Aug. 27. Praluent may generate $1.9 billion in sales for Sanofi in 2020, compared with $2.5 billion for Repatha, or evolocumab, analysts estimate.
The injections are meant to help difficult-to-treat patients.
Statins such as Pfizer Inc.’s Lipitor and Merck & Co.’s Zocor are the go-to treatment for high cholesterol, with one in four Americans at least 40 years old taking them, according to the National Center for Health Statistics. Yet about 15 percent of people on statins can’t tolerate them well because of muscle pain and weakness, according to an article in Circulation, an American Heart Association journal.