The race to successfully deliver a PCSK9 inhibitor to market for the treatment of hypercholesterolaemia intensified last week with Sanofi and Regeneron Pharmaceuticals unveiling a raft of new late-stage data for their antibody alirocumab.
Furthermore, via novel means (see ViewPoints: But what is an FDA priority review voucher actually worth? BioMarin finally puts a price tag on it), Sanofi and Regeneron appear to have closed the regulatory gap on Amgen, with the US biotech now expected to enjoy first-to-market status for its antibody evolocumab by only a matter of months, according to most estimates.
With Amgen expected to make its initial regulatory filings for evolocumab this quarter and Sanofi/Regeneron anticipating submissions for alirocumab by year end, 2015 is expected to see the PCSK9 class make its long awaited commercial debut – see also FirstWord Lists: Pharma's biggest pipeline drugs.
Regulatory and commercial uncertainties remain, however, with these issues primarily shaped by the demonstrated clinical profiles of both products based on an initial surrogate endpoint (LDL cholesterol reduction) and data from longer-term outcomes studies, which are not due to be published until 2018 onwards.
Although the suggestion that regulatory authorities will not approve products in the class until outcomes data is available have rescinded, debate centres on physician uptake during the first two years of availability based on LDL-C reduction (and the likely trend that usage will be heavily limited to harder to treat hypercholesterolaemia patients).
One potential overhang is data from Merck & Co.'s ongoing IMPROVE-IT study, which is evaluating the clinical benefit of Vytorin across 18000 patients. Should the study not demonstrate a benefit on outcomes (which many commentators and key opinion leaders believe is likely), will this have an impact on the FDA's willingness to approve PCSK9 inhibitors on LDL lowering alone and an impact on physician sentiment towards the PCSK9 class? The 'bull' argument is that LDL-C reduction is better understood than raised HDL levels and that Vytorin is unlikely to demonstrate such a high reduction in LDL-C.
Assuming approval is secured for both leading PCSK9 inhibitors without the requirement for outcomes data, there is limited differentiation between Amgen and Sanofi/Regeneron's products. One opportunity could stem from Amgen's more advanced development of once-monthly dosing (versus once every two weeks for Sanofi/Regeneron), although this requires a longer infusion process – a notable issue given that hypercholesterolaemia patients have typically been treated with oral therapies.
To provide further insight into how the early PCSK9 inhibitor market may evolve we are polling US and EU5-based cardiologists. Specifically we are asking them...
How comfortable they would be prescribing an experimental drug from the PCSK9 inhibitor class based on a surrogate endpoint of LDL reduction?
Whether negative data from the ongoing IMPROVE-IT study would have negative implications on their potential usage of the PCSK9 inhibitor class?
To what percentage of statin-intolerant hypercholesterolaemia patients (not at LDL goal) they would anticipate prescribing a PCSK9 inhibitor to two years after launch?
To what percentage of HeFH patients would you anticipate prescribing a PCSK9 inhibitor to two years after launch?
Which dosing regimen (once every two-weeks, which requires 1mL dosing with an auto-injector device, once-every four-weeks dosing, which requires three 1mL injections, or once every four weeks, which required one 10 minute infusion with a pager-sized device) they expect to prove most favourable among patients?
You will be able to read the results and analysis later this week.
Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.
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