FDA concerns relating to Repatha (evolocumab) and Praluent(alirocumab) for treatment of CV Risk- Amgen/Sanofi/Regeneron

FDA comments on Repatha and Praluent (alirocumab) from Sanofi/Regeneron have been similar in recognizing effectiveness in both drugs in lowering LDL-C but the FDA queries in what populations does LDL-C lowering benefits exceed risk? One risk seen by the FDA is the effect of encouraging patients to stop taking statins in favour of Repatha/Praluent which currently lack long term safety and CV data .The FDA waits the results of CV outcomes trials for both drugs and Amgen has produced some preliminary data from its FOURIER CVOT trial but complete results are not likely to be available until 2017.The FDA has previously accepted lowering of LDL-C as the benefit for reduction of CV risk without CV outcomes trials.

The FDA is taking advice from the Endocrinologic and Metabolic Drugs Advisory Committee whether evidence is adequate to approve the drugs in patients with different degrees of CV risk, familial versus non familial etiologies of hyperlipidaemia and use with or without concomitant statins. The FDA has also questions on the Repatha proposed dosing- 420 mg for Heterozygous Familial Hyperlipidaemia patients (which may include adolescents).The FDA notes that the Amgen choice of dosing is based on patient likely preferences rather than on titration linked to LDL magnitude. In low level LDL patients the choice may have to be made of use of other statins or discontinuation of Repatha. Safety concerns such as pancreatitis, renal disorders, new onset diabetes, musculoskeletal disorders adverse events, etc., could be addressed by labelling and monitoring.The PDUFA review date for Praluent is 24/7 and for Repatha is 27/8.

Comment: The CHMP has made a positive recommendation for Repatha.