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LDL in context

What FDA PCSK9 panel says about LDL as a surrogate of CV benefit

Discussion at last week's advisory committee meeting for the PCSK9 inhibitors Repatha evolocumab and Praluent alirocumab suggest that, for first-in-class hypercholesterolemia candidates, the agency and the committee are leaning toward narrowing the use of LDL as a surrogate endpoint to populations not well served by statins.

It appears likely that familial hypercholesterolemia (FH) is in, and - if the agency follows the panel's advice - the surrogate also may be acceptable for high-risk patients who are taking statins but continue to have heart attacks.

However, the outlook is unclear for populations such as statin-intolerant patients, and the panel was clear that it does not think LDL should be sufficient for patients with low baseline levels of the lipid.

The agency's decision on BLAs for Praluent from Sanofi and Regeneron Pharmaceuticals Inc. and Repatha from Amgen Inc. should clarify its thinking on several but not all of these populations.

Both BLAs are seeking indications that include monotherapy and combination therapy with statins or other lipid-lowering agents in heterozygous FH (heFH), other high-risk patients, and lower-risk patients with mixed dyslipidemia. Amgen is also seeking approval of Repatha to treat the Orphan disease homozygous FH (HoFH).

On June 9, the panel voted 13-3 to support approval of Praluent in at least one indication. Those 13 agreed the mAb should be approved for HeFH. Seven of the 13 also thought the candidate should be approved to treat high-risk patients whose LDL is not well controlled on maximally tolerated doses of statins.

On June 10, the panel voted 11-4 in favor of approval for Repatha in at least one indication, excluding HoFH, which was a separate voting question. Those 11 backed approval for HeFH, and eight also supported approval for the high-risk population not well controlled on statins.

All 15 panel members endorsed Repatha for HoFH.

The majority of panel members agreed that populations like HeFH and HoFH have a high unmet

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