Roche, Novo Nordisk and Merck Weigh in on FDA Draft Guidance on Assessment of Pressor Effects
Companies took issue with specific elements of the draft guidance advising sponsors on the premarketing assessment of a drug’s effect on blood pressure.Roche/Genentech explained, “While we agree with the spirit of the draft guidance with respect to ambulatory blood pressure monitoring (ABPM), we believe that a risk-based approach would better address the concern of potential drug-induced effects on blood pressure (BP) by reserving ABPM investigations ‘for cause’ (e.g., based on mechanism or action, high-risk population, or evidence of a blood pressure effect in early emerging data).”
The drugmaker made clear that smaller trials could have difficulties.
“Given the trend in drug development towards smaller, more targeted studies in rare subsets of disease and the challenges associated with recruiting patients for these studies, we note that it may be challenging to power such studies to detect blood pressure effects in the 2 to 3mm Hg range.”
Novo Nordisk, meanwhile, called on the US Food and Drug Administration to elaborate on “the use of home blood pressure measurements over 3 days as an alternative to ABPM. In general ABPM is challenging to use due to expensive equipment, time consuming mounting and de-mounting, data analysis and interpretation and affection of a patients every-day life during the measurement period.”
But Novo also said: “Serial in-office, resting cuff measurements during a trial visit or home BP measurements would not be sufficient in a large-scale study, which would be much more feasible for sponsors.”
The Danish company took issue with the draft’s treatment of the placebo group, saying, “It is acknowledged that there can be changes to blood pressure over time that could obscure drug effects, making inclusion of a placebo group desirable, however, there may be situations where a placebo group will not be feasible and it would be a mistake to have inclusion of a placebo group as a general requirement e.g. in disease areas where placebo treatment is not an option and/or unethical.”
Merck also noted that it would be helpful to know “if there are indications where the drug candidate would be used for chronic use but where life expectancy is limited and therefore the long-term impact on cardiovascular risk may not be a key factor in making a benefit-risk determination (e.g. oncology indications such as metastatic cancers).”
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