Sanofi and Regeneron Pharmaceuticals announced Wednesday top-line results from a Phase III study showing that the experimental PCSK9 inhibitor alirocumab reduced LDL cholesterol levels three times more than Merck & Co.'s Zetia (ezetimibe) in patients with primary hypercholesterolemia and moderate cardiovascular risk. "We are excited with the findings from the first Phase III trial with alirocumab," remarked Jay Edelberg, head of the PCSK9 Development and Launch Unit at Sanofi.
The ODYSSEY MONO trial randomised 103 patients to receive monotherapy with either alirocumab dosed initially at 75 mg every two weeks, and then up-titrated at week 12 to 150 mg if the LDL-C measurement at week 8 was above 70 mg/dL, or Zetia. Sanofi and Regeneron noted that "the majority" of patients remained on the initial dose of alirocumab because they achieved LDL-C below 70 mg/dL at week 8.
Results demonstrated that the study met its main goal, with alirocumab leading to LDL-C reductions of 47.2 percent from baseline to week 24, which was significantly greater than 15.6 percent for patients given Zetia. The companies said that adverse events were reported in 69.2 percent of patients in the alirocumab group, compared with 78.4 percent in those who received Zetia. The most common side effects were infections, including influenza and upper respiratory tract infections, which occurred in 42.3 percent of patients given alirocumab and 39.2 percent of patients who received Merck's drug.
Commenting on the findings, Regeneron's chief scientific officer George Yancopoulos said "the good news here is there were no surprises, and that it supports the good efficacy and safety profile we've seen to date." Edelberg suggested that alirocumab has so far shown "an unprecedented reduction in LDL," adding "it offers the promise of being able to get patients to and below their LDL targets." He noted that the fully-human monoclonal antibody is delivered via a single subcutaneous injection every two weeks. The auto-injector device "is designed to make the experience as easy for the patient as possible," Edelberg remarked.
Yancopoulos indicated that the companies plan to seek regulatory approvals by late 2015 for alirocumab after results from the remaining 11 late-stage trials are released. The ODYSSEY clinical programme for the drug is expected to enrol more than 23 000 patients, investigating alirocumab as a monotherapy and in combination with other lipid-lowering agents. Sanofi and Regeneron said that they plan to present detailed results from the ODYSSEY MONO study at a medical conference in 2014.
Citi analyst Andrew Baum noted that while the monotherapy data were "incrementally positive," further trials on targeted patient groups, such as those with high cardiovascular risk, were needed to really assess the drug's utility. Deutsche Bank added that the "results should go some way to building confidence in Sanofi's improving pipeline capability and in our view forms the first step to bridging credibility following recent poor financial results."
If approved, Robert W. Baird & Co. analysts predict that alirocumab could generate annual revenue of $717 million by 2017, while Alistair Campbell of Berenberg Bank estimated that the drug could reach sales of more than $3 billion by 2025. Robert W. Baird & Co. analysts suggest that Amgen's similar treatment AMG145 could generate revenue of $695 million by 2017. Yancopoulos said that Amgen's drug might reach the market soon after alirocumab, or even before, although he predicted that neither would have much of an advantage by gaining approval first. Other companies developing PCSK9 inhibitors include Alnylam Pharmaceuticals, Pfizer and Roche.
For results from a recent Physician Views Poll on PCSK9 inhibitors, see Awareness of PCSK9 inhibitors could be higher, but physicians ready to prescribe in hard-to-treat cardiovascular patients.
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