Sanofi and Regeneron have started enrolling patients in a large-scale phase III drug development programme that could mean an alternative to statin therapy for patients with high cholesterol.
Several trials have already got underway to evaluation SAR236553/REGN727, a first-in-class PCSK9 inhibitor that is delivered via a bi-weekly subcutaneous injection. Overall, Sanofi and Regeneron's ODYSSEY programme encompasses 10 trials and will enrol 22,000 patients.
The PCSK9 protein binds to and degrades receptors for LDL-cholesterol (LDL-c), causing elevated levels of LDL-c in the blood. Blocking the protein with REGN727 increases the number of receptors free to mop up circulating LDL-c.
Phase II trials of the drug showed that it could reduce LDL-c in patients with heterozygous familial hypercholesterolaemia (HeFH), a hard-to-treat inherited condition leading to elevated cholesterol that is resistant to statin therapy, as well as patients with primary hypercholesterolaemia.
Two trials in primary hypercholesterolaemia showed that REGN727 added to statin therapy achieved 40 to 72 per cent reductions in LDL-c compared to placebo, while a trial in HeFH patients achieved reductions of 28 to 68 per cent with Sanofi and Regeneron's drug.
ODYSSEY will recruit a broad range of patients, including those who are at elevated cardiovascular risk, are unable to tolerate statin therapy, or have familial hypercholesterolaemia, said the two companies.
"Despite the existence of very effective LDL-c lowering therapies, many patients… are unable to achieve their LDL-c goals," said Professor Henry Ginsberg of Columbia University Medical Centre in New York, who serves as chair of the ODYSSEY steering committee.
"Sustained PCSK9 blockade represents a potential new option to further reduce LDL-c on top of standard of care statin therapy and help patients achieve their LDL-c goals."
Sanofi and Regeneron are in the lead in the race to develop PCSK9-targeting therapies for high cholesterol, with other contenders still in early- to mid-stage testing. Analysts have suggested that REGN727 could achieve peak sales of $2.5bn-plus if it reaches the market as an add-on to statin therapy.
Amongst other contenders, Amgen has reached phase II with its AMG145 candidate, while Pfizer's RN316 and Novartis' LGT209 have also reached this stage of development.
BMS-844421, a compound targeting PCSK9 in development at Bristol-Myers Squibb and Isis Pharmaceuticals, was discontinued last year, as was a similar antisense-based drug from Santaris called SPC5001.
Alnylam Pharmaceuticals is now thought to be in the lead among companies trying the antisense route to PCSK9 inhibition, with a successful phase I trial of its ALN-PCS candidate reported earlier this year.