Recommendation comes despite safety concerns
An FDA advisory committee has recommended Sanofi and partner Isis Pharmaceuticals' Kynamro drug for a genetic form of high cholesterol, despite concerns about rates of cancer seen in trials.
The panel voted by 9 to 6 to recommend approval of Kynamro (mipomersen sodium) for the treatment of patients with homozygous familial hypercholesterolaemia (HoFH), a condition which causes patients to suffer aggressive heart disease at a very early age despite therapy.
Isis and Sanofi's Genzyme unit are seeking approval for the antisense drug as an adjunct to maximally-tolerated statin therapy in order to reduce low-density lipoprotein (LDL) and total cholesterol as well as other positive risk factors for heart disease such as apolipoprotein B (apoB) and apoA.
In trials, Kynamro given as a subcutaneous injection once a week achieved reductions in LDL-cholesterol of between 25 per cent and 37 per cent, but a high degree of variability between patients led the panel to describe the efficacy as "modest".
FDA documents published ahead of the committee meeting mentioned a fairly high drop-out rate for Kynamro compared to placebo, as well as an increase in benign and malignant tumours, which led to debate by panellists about the safety of the therapy.
In a conference call, Isis' chief executive Stanley Crooke insisted that analysis of data that compared incidence of tumours to exposure to the drug found no difference between Kynamro and placebo, and he rejected any idea that the company had withheld information from investors.
"An FDA reviewer came to a different interpretation [of the data]," he said. "Differences in interpretation of data particularly from such complex studies as these are a natural part of the scientific process."
There were also concerns about mipomersen's liver-related and cardiovascular side effects, which were the main reason for the negative votes, but on balance the committee decided Kynamro was an additional therapy option for a patient population that is very hard to treat.
The vote "marks a significant and positive step in our efforts to bring this important new therapy to patients and families affected by this often unrecognised genetic disorder", commented David Meeker, Genzyme's president.
"There is still a great need for the HoFH patients, who have exhausted conventional medications and still have LDL-cholesterol levels 2-4 times above normal," he added.
Aegerion's lomitapide also backed
The panel voted on Kynamro a day after backing Aegerion Pharmaceuticals' orally-active drug lomitapide for HoFH.
The committee said lomitapide was safe and effective when used with a low-fat diet and other therapies to reduce patients' cholesterol levels, with or without LDL apheresis, a dialysis-like procedure in which LDs are removed from the blood.
Analysts have predicted that both Kynamro and lomitapide could achieve sales of in the $300m to $500m range at peak.