2:54 PM
 | 
Nov 09, 2018
 |  BioCentury  |  Product Development

Cashing out CVOT

Why eliminating CVOTs may not save diabetes companies as much money as it seems

Whether or how much diabetes companies will save by dropping postmarket cardiovascular outcomes trials, if FDA follows the advice of its advisory committee, could boil down to what target they are pursuing and whether they are planning for a label claim of cardiovascular benefit.

The consensus of the Oct. 25 meeting of FDA’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) was that the overall requirements for demonstrating CV safety should be lowered. Postmarket CV outcome trials (CVOTs), most panel members argued, should be required only when a premarket signal arises that warrants further characterization.

But in lieu of a postmarket CVOT, panelists wanted to see more thorough premarket safety evaluation.

FDA’s current guidance requires preapproval studies showing a therapy does not increase the risk of CV events by 80% or more. EMDAC did not specify how much additional CV risk should be ruled out in the premarket setting.

The panel also recommended switching from placebo-controlled trials to ones that use an active comparator and non-inferiority design.

Dropping the requirement for post-market CVOT could save companies $200-$500 million per trial.

But ruling out additional CV risk and adopting non-inferiority trials would mean expanding the number of patients enrolled into Phase III trials, which could add more than $100 million in development costs.

Companies working on products that have the potential to be cardioprotective -- such as glucagon-like peptide-1 (GLP-1) agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors -- might still choose to run CVOTs, making the overall costs of development higher, but there would be commercial upside from the claim of CV benefit.

Companies with cardioneutral compounds such as dipeptidyl peptidase-4 (DPP-4; CD26) inhibitors would likely have net savings despite increased premarket development costs, but to compete commercially would need to show benefits on other comorbidities.

How the math works out will depend on at least three factors: what the new risk threshold turns out to be, whether FDA allows companies to make changes to...

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